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- Vermeulen, Robert P, et al.
(author)
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Clinical correlates of arterial lactate levels in patients with ST-segment elevation myocardial infarction at admission : a descriptive study
- 2010
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 14:5, s. R164-
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Journal article (peer-reviewed)abstract
- ABSTRACT : INTRODUCTION : Blood lactate measurements can be used as an indicator of hemodynamic impairment and relate to mortality in various forms of shock. Little is known at the moment concerning the clinical correlates of systemic lactate in patients with ST-segment elevation myocardial infarction (STEMI). METHODS : To assess the relation of systemic arterial lactate levels in STEMI patients with clinical correlates at presentation in the catheterization laboratory, we measured arterial lactate levels with a rapid point-of-care technique, immediately following femoral sheath insertion. The study population (n= 1,176) was divided into tertiles with lactate levels ≤1.1 (n = 410), 1.2 to 1.7 (n = 398) and ≥1.8 mmol/l (n = 368). We compared both baseline characteristics and outcome measures of the three lactate groups. RESULTS : Factors independently associated with higher lactate levels were hypotension, heart rate, thrombolysis in myocardial infarction (TIMI) flow 0 to 1, diabetes and non-smoking. Mortality at 30 days in the three groups was 2.0%, 1.5% and 6.5%. The latter group also showed lower blush grades and greater enzymatic infarct sizes. An intra aortic balloon pump (IABP) was used more frequently in patients with higher lactate levels (4.2%, 7.6% and 14.7%). CONCLUSIONS : In STEMI patients, impaired hemodynamics, worse TIMI flow and non-smoking were related to increased arterial lactate levels. Higher lactate levels were independently related with 30-day mortality and an overall worse response to percutaneous coronary intervention (PCI). In particular, acute mortality was related to admission lactates ≥1.8 mmol/L. Point-of-care measurement of arterial lactate at admission in patients with STEMI has the potential to improve acute risk stratification.
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- Gabba, Adele, et al.
(author)
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MUC1 glycopeptide vaccine modified with a GalNAc glycocluster targets the macrophage galactose c-type lectin on dendritic cells to elicit an improved humoral response
- 2023
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 145:24, s. 13027-13037
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Journal article (peer-reviewed)abstract
- Mucin expression and glycosylation patterns on cancer cells differ markedly from healthy cells. Mucin 1 (MUC1) is overexpressed in several solid tumors and presents high levels of aberrant, truncated O-glycans (e.g., Tn antigen). Dendritic cells (DCs) express lectins that bind to these tumor-associated carbohydrate antigens (TACAs) to modulate immune responses. Selectively targeting these receptors with synthetic TACAs is a promising strategy to develop anticancer vaccines and to overcome TACA tolerance. In this work, we prepared, via a solid phase peptide synthesis approach, a modular tripartite vaccine candidate, incorporating a high-affinity glycocluster based on a tetraphenylethylene scaffold, to target the macrophage galactose-type lectin (MGL) on antigen presenting cells. MGL is a C-type lectin receptor that binds Tn antigens and can route them to human leukocyte antigen class II or I, making it an attractive target for anticancer vaccines. Conjugation of the glycocluster to a library of MUC1 glycopeptides bearing the Tn antigen is shown to promote uptake and recognition of the TACA by DCs via MGL. In vivo testing revealed that immunization with the newly designed vaccine construct bearing the GalNAc glycocluster induced a higher titer of anti-Tn-MUC1 antibodies compared to the TACAs alone. Additionally, the antibodies obtained bind a library of tumor-associated saccharide structures on MUC1 and MUC1-positive breast cancer cells. Conjugation of a high-affinity ligand for MGL to tumor-associated MUC1 glycopeptide antigens has a synergistic impact on antibody production.
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