External beam radiation after stent implantation increases neointimal hyperplasia by augmenting smooth muscle cell proliferation and extracellular matrix accumulation

AbstractOBJECTIVESWe sought to examine the effects of high volume external beam radiation (EBR) after stent implantation on neointimal hyperplasia, smooth muscle cell (SMC) proliferation, presence of inflammatory cells and expression of extracellular matrix (ECM).BACKGROUNDEndovascular irradiation has been shown to reduce restenosis rates after angioplasty in preliminary trials, but conflicting results have been reported for the effects of external beam irradiation.METHODSForty-three Palmaz-Schatz stents were implanted into iliac arteries of New Zealand White rabbits. The arteries were externally irradiated after stent implantation with a single dose of 8 Gy (at day 3) or 16 Gy in two fractions (8 Gy at days 3 and 4) by means of a linear accelerator. In the control rabbits, no radiation was applied after stent implantation. Smooth muscle cells, macrophages and ECM were studied by immunohistochemistry at one and 12 weeks after stent implantation. Collagen type I and biglycan messenger ribonucleic acid (mRNA) levels were assessed by Northern blot analysis at one week. Neointimal cell densities and arterial lumen stenosis were measured by histomorphometry at 12 weeks.RESULTSAt 1 week, SMC proliferation at the site of stent implantation was increased after EBR with 8 and 16 Gy (26 ± 5%, 32 ± 3% vs. 17 ± 8%; p < 0.01, 16 Gy vs. control). External beam radiation with 8 and 16 Gy augmented SMC proliferation proximal and distal to the angioplasty site (11 ± 3%, 14 ± 3 vs. 6 ± 1%; p < 0.01, 16 Gy vs. control). Collagen type I and biglycan mRNA levels were elevated in stented arteries after EBR with 16 Gy. At 12 weeks, a marked decrease in neointimal cell density (248 ± 97 vs. 498 ± 117 SMCs/0.1 mm2neointima; p < 0.005 vs. control) was noted after EBR with 16 Gy. Irradiation with 8 and 16 Gy increased arterial lumen stenosis compared with nonirradiated control rabbits (45 ± 7%, 55 ± 9% vs. 33 ± 7%; p < 0.05, 8 Gy and p < 0.001, 16 Gy vs. control).CONCLUSIONSHigh volume external beam radiation at doses of 8 or 16 Gy causes restenosis by augmenting proliferative activity at and adjacent to the site of stent implantation, and by dose-dependent up-regulation of extracellular matrix expression. The study suggests that excessive matrix accumulation is an important determinant of failure of radiation therapy to prevent restenosis

Triple Antithrombotic Therapy after Percutaneous Coronary Intervention (PCI) in Patients with Indication for Oral Anticoagulation: Data from a Single Center Registry.

Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple therapy. This combined anticoagulation is applied in patients undergoing coronary artery stent implantation while also having an indication for OAC. Triple therapy increases the risk for bleeding events compared to either DAPT or OAC alone and thereby might be associated with adverse outcomes. Clinical data on the frequency of bleeding events in patients on triple therapy from clinical trials derives from pre-selected patients and may differ from the real world patients. We report data on patient characteristics and bleeding incidence of patients dismissed on triple therapy from a single university hospital. Within the time span from January 2000 to December 2012, we identified a total of 213 patients undergoing PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86% of all patients treated). The usage of triple therapy significantly increased over the observed time period. The average CHA2DS2-VASc Score was 3.1 ± 1.1 with an average HAS-BLED score of 2.5 ± 0.86 representing a high-risk group for thromboembolic events as well as considerable risk for bleeding events. An on-treatment bleeding incidence of 9.4% was detected, with gastrointestinal and airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is consistent with data from clinical trials and confirms the high risk of bleeding in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had an indication for OAC other than non-valvular atrial fibrillation. This substantial patient group is underrepresented by clinical trials and needs further attention

Number of patients discharged on triple therapy by year.

<p>Number of patients discharged on triple therapy by year.</p

Distribution of the CHA₂DS₂-VASc and the HAS-BLED Score of all patients on triple therapy.

<p>Distribution of the CHA₂DS₂-VASc and the HAS-BLED Score of all patients on triple therapy.</p

Screening algorithm of patients on triple therapy after stent implantation.

<p>A total of 24892 patients were treated within 2000 and 2012. A computerized search returned 1244 hits of which 213 were actually discharged on triple therapy. Complete data is available on 138 patients.</p

Distribution of proton pump inhibitor usage of all patients and of patients with bleeding events.

<p>PPI: proton pump inhibitor.</p

Distribution of bleeding events of patients on triple therapy by bleeding site.

<p>Distribution of bleeding events of patients on triple therapy by bleeding site.</p

Weakness of lower limb muscle in symptomatic peripheral artery disease with media sclerosis detected by ultrasound shear wave elastography

&lt;jats:p&gt; Zusammenfassung. Der in der TEDS-M-Studie (Teacher Education and Development Study: Learning to Teach Mathematics) entwickelte Test zur Erfassung pädagogischen Wissens am Ende der Lehramtsausbildung hat sich in diversen Untersuchungen als zuverlässiges Messinstrument erwiesen, für das eine Reihe von Ergebnissen vorliegt, die die Validität der Testwertinterpretationen bei (angehenden) Lehrkräften in unterschiedlichen Ausbildungsstadien und –kontexten unterstreichen. Ein wesentlicher Validierungsschritt steht jedoch noch aus: Die Überprüfung, ob sich der Test eignet, um quantitative und qualitative Aussagen zum pädagogischen Wissen von berufstätigen Mathematiklehrkräften zu treffen. Im Rahmen des Projekts TEDS-Validierung wurde an 113 Mathematiklehrkräften geprüft, ob der Test das Wissen der Lehrkräfte reliabel und differenziert erfasst. Darauf aufbauend wurde im Sinne der Konstruktrepräsentation ( Embretson, 1983 ) untersucht, ob er konstruktrelevante, kognitive Bearbeitungsprozesse erfordert, wie sie von König (2009) und Klemenz und König (2019) modelliert wurden. Die Analysen bestätigen, dass der Test auch bei berufstätigen Mathematiklehrkräften ein reliables Messinstrument darstellt und unterstreichen, dass die kognitive Komplexität der erforderlichen Bearbeitungsprozesse einen bedeutsamen Anteil der Schwierigkeitsvarianz aufklärt. Sie liefern somit einen ersten Hinweis für die Konstruktrepräsentation und die Grundlage für eine qualitative Interpretation der Testwerte. Diese Interpretation wird durch Varianzanalysen validiert, die zeigen, dass Personen, die kognitiv komplexere Bearbeitungsprozesse im pädagogischen Wissenstest vollziehen können, auch ausgeprägtere situationsspezifische, pädagogische Fähigkeiten aufweisen als Vergleichspersonen. &lt;/jats:p&gt

Final results of a phase IIa, randomised, open-label trial to evaluate the percutaneous intramyocardial transplantation of autologous skeletal myoblasts in congestive heart failure patients: the SEISMIC trial.

peer reviewedAIMS: The SEISMIC study was an open-label, prospective, randomised study to assess the safety and feasibility of percutaneous myoblast implantation in heart failure patients with implanted cardioverter-defibrillators (ICD). METHODS AND RESULTS: Patients were randomised 2:1 to autologous skeletal myoblast therapy vs. optimal medical treatment. The primary safety end-point was defined as the incidence of procedural and device related serious adverse events, whereas the efficacy endpoints were defined as the change in global LVEF by MUGA scan, change in NYHA classification of heart failure and in the distance achieved during a six-minute walk test (6MW) at 6-month follow-up. Forty subjects were randomised to the treatment arm (n=26), or to the control arm (n=14). There were 12 sustained arrhythmic events and one death after episodes of ventricular tachycardia (VT) in the treatment group and 14 events in the control group (P=ns). At 6-month follow-up, 6MW distance improved by 60.3+/-54.1?meters in the treated group as compared to no improvement in the control group (0.4+/-185.7?meters; P=ns). In the control group, 28.6% experienced worsening of heart failure status (4/14), while 14.3% experienced an improvement in NYHA classification (2/14). In the myoblast-treatment arm, one patient experienced a deterioration in NYHA classification (8.0%), whereas five patients improved one or two classes (20.0%; P=0.06). However, therapy did not improve global LVEF measured by MUGA at 6-month follow-up. CONCLUSIONS: These data indicate that implantation of myoblasts in patients with HF is feasible, appears to be safe and may provide symptomatic relief, though no significant effect was detected on global LVEF