ObjectivesWe hypothesised that patients having experienced one coronary event in their life were susceptible to present differences in their pathways of care and within 1 year of their life courses. ...We aimed to compare pathways between first-time ST-elevation myocardial infarction (STEMI) and STEMI with prior myocardial infarction (MI).DesignA retrospective observational study based on the Observatoire des Syndromes Coronariens Aigus du réseau RESCUe (OSCAR) registry collecting all suspected STEMI from 10 percutaneous coronary intervention centres in France.SettingAll patients with STEMI from 2013 to 2017 were included (N=6306 with 5423 first-time STEMI and 883 STEMI with prior MI). We provided a matching analysis by propensity score based on cardiovascular risk factors.ParticipantsWe defined first-time STEMI as STEMI occurring at the inclusion date, and STEMI with prior MI as STEMI with a history of MI prior to the inclusion date.ResultsPatients with first-time STEMI and patients with STEMI with prior MI were equally treated during hospitalisation and at discharge. At 12 months, patients with first-time STEMI had a lower adherence to BASIC treatment (ie, beta-blocker, antiplatelet therapy, statin and converting enzyme inhibitor) (48.11% vs 58.58%, p=0.0167), more frequently completed the cardiac rehabilitation programme (44.33% vs 31.72%, p=0.0029), more frequently changed their lifestyle behaviours; more frequently practiced daily physical activity (48.11% vs 35.82%, p=0.0043) and more frequently stopped smoking at admission (69.39% vs 55.00%, p=0.0524). The estimated mortality was higher for patients with STEMI with prior MI at 1 month (p=0.0100), 6 months (p=0.0500) and 1 year (p=0.0600).ConclusionsWe provided an exhaustive overview of the real-life clinical practice conditions of STEMI management. The patients with STEMI with prior MI presented an optimised use of prehospital resources, which was probably due to their previous experience, and showed a better adherence to drug therapy compared with patients with first-time STEMI.Trial registration numberCommission Nationale de l’Informatique et des Libertés (number 2 013 090 v0).
Transcatheter aortic valve replacement (TAVR) is standard therapy for patients with severe aortic stenosis who are at high surgical risk. However, national data regarding procedural characteristics ...and clinical outcomes over time are limited.
The aim of this study was to assess nationwide performance trends and clinical outcomes of TAVR during a 6-year period.
TAVRs performed in 48 centers across France between January 2013 and December 2015 were prospectively included in the FRANCE TAVI (French Transcatheter Aortic Valve Implantation) registry. Findings were further compared with those reported from the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry, which captured all TAVRs performed from January 2010 to January 2012 across 34 centers.
A total of 12,804 patients from FRANCE TAVI and 4,165 patients from FRANCE 2 were included in this analysis. The median age of patients was 84.6 years, and 49.7% were men. FRANCE TAVI participants were older but at lower surgical risk (median logistic European System for Cardiac Operative Risk Evaluation EuroSCORE: 15.0% vs. 18.4%; p < 0.001). More than 80% of patients in FRANCE TAVI underwent transfemoral TAVR. Transesophageal echocardiography guidance decreased from 60.7% to 32.3% of cases, whereas more recent procedures were increasingly performed in hybrid operating rooms (15.8% vs. 35.7%). Rates of Valve Academic Research Consortium–defined device success increased from 95.3% in FRANCE 2 to 96.8% in FRANCE TAVI (p < 0.001). In-hospital and 30-day mortality rates were 4.4% and 5.4%, respectively, in FRANCE TAVI compared with 8.2% and 10.1%, respectively, in FRANCE 2 (p < 0.001 for both). Stroke and potentially life-threatening complications, such as annulus rupture or aortic dissection, remained stable over time, whereas rates of cardiac tamponade and pacemaker implantation significantly increased.
The FRANCE TAVI registry provided reassuring data regarding trends in TAVR performance in an all-comers population on a national scale. Nonetheless, given that TAVR indications are likely to expand to patients at lower surgical risk, concerns remain regarding potentially life-threatening complications and pacemaker implantation. (Registry of Aortic Valve Bioprostheses Established by Catheter FRANCE TAVI; NCT01777828)
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OBJECTIVESTo report 5-fluorouracil in combination with folinic acid as a cause of severe nonischemic heart failure and to demonstrate the potential usefulness of an intra-aortic balloon pump.
...DESIGNCase report.
SETTINGAn adult, 19-bed medical/surgical intensive care unit of a university hospital.
PATIENTSA patient, who developed severe heart failure secondary to 5-fluorouracil infusion with low-dose folinic acid, which was introduced to treat a rectal cancer, was transferred from a cancer institute to our intensive care unit 4 days after the treatment was initiated.
INTERVENTIONSElectrocardiography, determination of level of cardiac enzymes, echocardiography, radial arterial catheterization, mechanical ventilatory support, continuous venovenous hemodialysis, vasopressors, and secondary intra-aortic balloon pump.
MEASUREMENT AND MAIN RESULTSDuring shock, the patient’s systolic blood pressure progressively decreased to 70 mm Hg, despite inotropic agents and vasopressors. Transesophageal echocardiography showed a calculated left ventricular ejection fraction within 20% with global hypokinesia. Electrocardiography showed sinus tachycardia with only nonspecific ST-T changes. Results of serial determination of levels of cardiac enzymes were not significant for myocardial infarction. Treatment with an intra-aortic balloon pump was initiated and resulted in a dramatical improvement within 48 hrs. The patient was gradually weaned from vasopressors and the intra-aortic balloon pump. By the tenth day, echocardiography showed a septoapical hypokinesia with a 50% left ventricular ejection fraction. On the 30th day, the echocardiography was considered normal.
CONCLUSIONIntravenous 5-fluorouracil in combination with low doses of folinic acid can induce severe nonischemic heart failure. In such a case, an intra-aortic balloon pump could be useful by providing left ventricular function support when inotropic agents and vasopressors fail to restore normal hemodynamics. (Crit Care Med 2000; 28:3558–3560)
Abstract
Immunomodulating agents have revolutionized anti-cancer therapy. However, monotherapy is often not sufficient, and development of combination treatments is hampered by cumulative toxicity. ...In an attempt to overcome this challenge, a tumor-restricted agonistic 4-1BB/FAP DARPin drug candidate, which induces T-cell co-stimulation only when clustered by binding to fibroblast activation protein alpha (FAP) expressing cells, has been developed. FAP is a type II membrane-bound glycoprotein abundantly expressed in the stroma of many solid tumors by cancer-associated fibroblasts. As shown previously using in vitro and in vivo models (HT-29), co-stimulation induced by a FAP-targeted 4-1BB agonistic DARPin molecule leads to enhanced activation and expansion of CD8+ T-cells. To support clinical development of the drug candidate, tumor localization and accumulation were studied by whole-body SPECT/CT imaging and quantitative biodistribution using Indium-111 labeled DARPin molecules in a human colorectal adenocarcinoma (HT-29) xenograft model in CD1 nude mice. Immunohistochemical staining of tumor stroma confirmed local expression of FAP. Labeled 4-1BB/FAP DARPin molecules specifically accumulated in FAP-expressing tumor in vivo. SPECT/CT imaging and biodistribution revealed a maximum tumor accumulation of around 15% of the injected dose per gram of tissue around 72 h post injection. High tumor/blood ratios were observed one week post injection because the activity in the blood decreased according to the expected serum half-life of 26 h, determined in separate pharmacokinetic studies in BALB/c mice following single dose intravenous bolus injections. Based on the decrease of radioactivity in the tumor, a tumor residence half-life of approximately 4 days was calculated, indicating an extended tumor retention potentially due to FAP binding. No accumulation was observed in the muscle tissue that was choosen as a rather weakly-perfused control tissue. Taken together, FAP-targeting of a 4-1BB agonist DARPin molecule resulted in expected high tumor accumulation and retention compared to an untargeted version of the molecule, both relevant observations for further preclinical and clinical studies. These findings suggest that tumor-targeting via FAP has the potential to induce T-cell activation restricted to the tumor site, and thereby reducing toxicities caused by systemic 4-1BB activation. In conclusion, immunostimulatory drugs with tumor-targeted activity may have the potential to circumvent current limitations of immunotherapy and allow safe and effective use, in particular in combination therapy.
Citation Format: Christian Reichen, Ralph Bessey, Christine DePasquale, Stefan Imobersteg, Martin Behe, Alain Blanc, Roger Schibli, Alexander Link, Laurent Juglair, Joanna Taylor, Patricia Schildknecht, Julia Hepp, Elmar vom Baur, Hong Ji, Christof Zitt, Victor Levitsky, Keith M. Dawson, Michael T. Stumpp, Dan Snell. FAP-mediated tumor accumulation of a T-cell agonistic FAP/4-1BB DARPin drug candidate analyzed by SPECT/CT and quantitative biodistribution abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3029.
This book presents a comprehensive introduction to X -ray and neutron reflectivity techniques and illustrates them with many examples. For the second edition, all chapters have been thoroughly ...revised, updated and, where appropriate, suitably augmented.
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