DO STUDY RESULTS TRANSLATE INTO PRACTICE? INTRACRANIAL STENTING IN GERMANY.

OBJECTIVES: Enrolment into the SAMMPRIS trial published in September 2011 had to be stopped due to a 2.5 higher 30-day stroke and death rate in patients with percutaneous transluminal angioplasty and stenting (PTAS) compared with the control group with only medical therapy. After these results were published, one would have expected a change toward a clearer definition of indications for intracranial stent implantation in patients with intracranial artery stenosis, using this treatment only in patients suffering from recurrent strokes despite aggressive medical management. METHODS: The frequency of intracranial stenting and indication parameters in patients with intracranial artery stenosis were assessed from 2010 to 2013 using claims data for all inpatient episodes from Germany's largest provider of statutory health insurance. RESULTS: The number of intracranial stenting procedures decreased slowly from 580 in 2010 to 375 in 2013. With a rate of 29 percent there was no change between 2010 and 2013 of patients who were admitted to hospital for stent implantation, without documentation of an acute stroke or transient ischemic attack (TIA). Before PTAS, one-third of patients were admitted twice because of a stroke or TIA over a period of 5 years, 17 percent of patients had been prescribed platelet aggregation inhibitors and at least two admissions to hospital were for an ischemic cerebrovascular event before PTAS. CONCLUSIONS: Our analysis of German claims data provides little evidence of changed indications for stenting in cases of intracranial atherosclerotic disease which one might expect to be caused by the emergence of high-level evidence.

Prospective evaluation of a Holter-ECG derived severity index for screening of sleep disordered breathing.

BACKGROUND AND PURPOSE: To prospectively evaluate the applicability of a method to screen overnight Holter-ECGs for sleep disordered breathing (SDB) in an unselected clinical routine Holter sample. METHODS: Holter-ECG recordings in 50 cardiologic inpatients were complemented with nocturnal respiratory polygraphy (PG). The respiratory event index (REI) and apnea/hypopnea index (AHI) from the PG served as a reference for an ECG-derived SDB severity estimate using a previously developed method. Agreement with the PG was investigated using Bland-Altman plots color-coded by ectopy level, and screening accuracy for REI≥15/h and AHI≥15/h was assessed. RESULTS: Prevalence for REI≥15/h was 52%, and 32% for AHI≥15/h. We observed better agreement of the ECG-based estimate with the REI compared to the AHI. Ectopy did not limit the detection of SDB. Binary screening for REI≥15/h provided excellent specificity of 0.96 with a sensitivity of 0.77. Ternary screening for AHI≥15/h yielded 16% borderline classifications and specificity/sensitivity of 0.96/0.86 for the remaining data. CONCLUSIONS: Screening of routine Holter-ECGs for sleep disordered breathing is reasonable and promises earlier identification of a significant part of patients at no additional cost.

Dried Blood Spot Technique for the Monitoring of Ambrisentan, Bosentan, Sildenafil, and Tadalafil in Patients with Pulmonary Arterial Hypertension.

Endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitors (PDE5I) are long-term therapeutics for the treatment of pulmonary arterial hypertension (PAH). Their interindividual pharmacokinetic variability is remarkably large, and despite the seriousness of the disease, nonadherence is occurring. Therefore, methods to monitor sufficient circulating drug levels are essential. The objectives of this study were to develop and validate dried blood spot (DBS) assays for the quantification of ambrisentan, bosentan, sildenafil, tadalafil, and their main metabolites. We also quantified the influence of different hematocrit levels and assessed the correlation of simultaneously taken capillary whole blood (DBS) and venous plasma samples. The aliquot punches were extracted by liquid/liquid extraction followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) quantification methods. All assays fulfilled the requirements of the FDA and EMA guidelines for assay validation with a lower limit of quantification of 2.5 ng/mL for the ERAs, 5 ng/mL for sildenafil, and 10 ng/mL for tadalafil. All analytes were stable for at least 147 days when stored on DBS filter paper cards at room temperature in the dark. Due to poor distribution into erythrocytes, drug concentrations in DBS were always lower than in plasma, resulting in conversion factors of 1.58 for ambrisentan and sildenafil and 1.52 for bosentan and tadalafil.

Novel biomarkers for risk stratification in pulmonary arterial hypertension.

Risk stratification in pulmonary arterial hypertension (PAH) is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH. 95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T (hsTnT), pro-atrial natriuretic peptide (proANP), growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4%) patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal pro-brain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR) 1.91), hsTnT (HR 1.41), echocardiographic right ventricular impairment (HR 1.30) and 6-min walk test (HR 0.97 per 10 m) remained the only significant parameters in prognostication of mortality. Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH.

Reaction of water with (radicals in) plasma polymerized allyl alcohol (and formation of OH-rich polymer layers).

The pulsed plasma polymerization of allyl alcohol was employed under the aspect of maximal retention of OH groups and the formation of a regular polymer structure. It should be noted that earlier investigations on plasma polymers deposited from allyl alcohol did not show extensive postplasma addition of oxygen and water vapor from ambient air during storage, measuring the elemental O/C ratio by means of X-ray photoelectron spectroscopy (XPS).The identification of OH groups in the plasma polymerized polymer using FTIR spectroscopy was such an indicator for fragmentation. The peak area of OH groups in the film which was stored was increased by about 20% compared to that measured ("in situ"). These phenomenons reflected that moisture and O2 in air played an important role in scavenging the free radicals. The addition of water and more specifically chemical bonding of OH of water in the deposited plasma polymer may serve as an indicator for monomer fragmentation, poly recombination, and the remaining radicals responsible for film formation. Moreover, the dielectric measurements show that the plasma deposited films are not thermally stable but undergo a postplasma chemical reaction during heating, where the reaction kinetics depends on pressure.

Impact of polymer shell on the formation and time evolution of nanoparticle-protein corona.

The study of protein corona formation on nanoparticles (NPs) represents an actual main issue in colloidal, biomedical and toxicological sciences. However, little is known about the influence of polymer shells on the formation and time evolution of protein corona onto functionalized NPs. Therefore, silica-poly(ethylene glycol) core-shell nanohybrids (SNPs@PEG) with different polymer molecular weights (MW) were synthesized and exhaustively characterized. Bovine serum albumin (BSA) at different concentrations (0.1-6 wt%) was used as model protein to study protein corona formation and time evolution. For pristine SNPs and SNPs@PEG (MW=350 g/mol), zeta potential at different incubation times show a dynamical evolution of the nanoparticle-protein corona. Oppositely, for SNPs@PEG with MW≥2000 g/mol a significant suppression of corona formation and time evolution was observed. Furthermore, AFM investigations suggest a different orientation (side-chain or perpendicular) and penetration depth of BSA toward PEGylated surfaces depending on the polymer length which may explain differences in protein corona evolution.

UV Spectrometric Indirect Analysis of Brominated MWCNTs with UV Active Thiols and an Alkene-Reaction Kinetics, Quantification and Differentiation of Adsorbed Bromine and Oxygen.

Indirect UV-absorption spectrometry was shown to be a valuable tool for chemical characterization of functionalized carbon nanotubes (CNTs). It complements data from X-ray photoelectron spectroscopy (XPS) or FTIR analysis since it helps to clarify the type and concentration of functional groups. The principles of indirect application of UV-spectrometry and its mathematical interpretation are discussed. Their facile application, together with their adequate sensitivity and high flexibility, make UV-absorption-based approaches a valuable alternative to fluorescence spectrometry. Here, the approach was applied to the chemical analysis of oxidizing substances on CNTs. For this, pristine CNTs of low but finite oxygen content as well as brominated CNTs were analyzed by reaction in suspension with UV-active thiol reagents and a styrene derivative. It was shown that carefully selected reagents allow differentiation and quantification of bromine and generally oxidizing entities like oxygen. For brominated CNTs, it was shown that physisorbed bromine may dominate the overall bromine content.

Fate of patients with prehospital resuscitation for ST-elevation myocardial infarction and a high rate of early reperfusion therapy (results from the PREMIR [Prehospital Myocardial Infarction Registry]).

Patients with acute ST-segment elevation myocardial infarction (STEMI) needing prehospital cardiopulmonary resuscitation (CPR) have a very high adverse-event rate. However, little is known about the fate of these patients and predictors of mortality in the era of early reperfusion therapy. From March 2003 through December 2004, 2,317 patients with prehospital diagnosed STEMI were enrolled in the Prehospital Myocardial Infarction Registry. One hundred ninety patients (8.2%) underwent prehospital CPR and were included in our analysis. Overall 90% of patients were treated with early reperfusion therapy, 56.3% received prehospital thrombolysis and 1/2 of these patients received early percutaneous coronary intervention after thrombolysis, 28.4% of patients were treated with primary percutaneous coronary intervention, and 5.3% received in-hospital thrombolysis. Total mortality was 40.0%. The highest mortality was seen in patients with asystole (63%) or pulseless electric activity (64%). Independent predictors of mortality were need for endotracheal intubation and older age, whereas ventricular fibrillation as initial heart rhythm was associated with survival. In conclusion, in this large registry with prehospital diagnosed STEMI, incidence of prehospital CPR was about 8%. Even with a very high rate of early reperfusion therapy, in-hospital mortality was high. Especially in elderly patients with asystole as initial heart rhythm and with need for endotracheal intubation, prognosis is poor despite aggressive reperfusion therapy.