AIMS:Acute myocardial infarction (MI) induces a systemic inflammatory response that usually resolves within days, but the prognostic impact of persistent inflammation is uncertain. We assessed whether sustained leukocytosis after ST-segment elevation myocardial infarction (STEMI) relates to infarct size, left ventricular function, and clinical outcomes. METHODS AND RESULTS:In >1,700 STEMI patients treated with primary percutaneous coronary intervention, leukocytes peaked on admission and typically normalized by day 3. Patients were stratified by leukocyte tertiles at admission and day 3. High day 3 leukocyte counts were associated with larger infarct size (scintigraphy; peak creatine kinase-myocardial band and troponin T), worse left ventricular function in hospital and at 6 months, and higher 1- and 5-year mortality. Patients whose leukocyte counts declined had better recovery, whereas persistent leukocytosis marked the poorest outcomes. Monocyte RNA sequencing showed post-MI transcriptomic reprogramming, and murine MI models recapitulated a similar systemic immune response. CONCLUSIONS:Persistent inflammation, particularly elevated leukocyte counts at day 3 post-MI, is associated with adverse remodeling and increased mortality after STEMI, identifying unresolved inflammation as a negative prognostic marker and potential therapeutic target.
BACKGROUND:Atherosclerotic plaque destabilization is promoted by inflammatory cell recruitment, tissue cell death, and mechanical weakening. Neutrophils drive vascular tissue injury and perpetuate inflammation and represent a viable therapeutic opportunity. Here, we identify a distinct subset of activated neutrophils within atherosclerotic lesions that express the chemokine receptor CCR2 (C-C chemokine receptor type 2), which directs their migration toward areas enriched with smooth muscle cells and contributes to plaque instability. METHODS:Flow cytometry and single-cell transcriptomic analysis of CCR2+ neutrophils within murine and human atherosclerotic plaques. Tracking of CCR2+ neutrophil in hypercholesterolemic Ldlr-/- mice and in mice reconstituted with Ccr2GFP/- bone marrow. In vivo reactive oxygen species and neutrophil extracellular trap analysis in lipopolysaccharide-induced peritonitis. In vitro migration assays of neutrophils deficient for or treated with a specific antagonist against chemokine receptors. In vivo neutrophil recruitment and features of atherosclerotic plaque vulnerability analysis on CCR2 and CCL2 (C-C motif chemokine ligand 2) blockade in a model of advanced atherosclerosis in Apoe-/- mice. RESULTS:CCR2+ neutrophils preferentially populate mouse and human atherosclerotic lesions and display a proinflammatory phenotype with enhanced capacity for reactive oxygen species production and neutrophil extracellular trap release. Genetic or pharmacological CCR2 inhibition reduced neutrophil migration and infiltration to the atherosclerotic lesion, reducing their presence in smooth muscle cell-rich areas. Consistently, neutralization of the CCR2 ligand CCL2 decreased lesional neutrophil numbers and preserved fibrous cap integrity by increasing smooth muscle cell content and decreasing features associated with plaque instability. CONCLUSIONS:Our data suggest that a subset of CCR2-expressing neutrophils senses smooth muscle cell-derived CCR2 ligands to infiltrate and promote vulnerable atherosclerotic lesions. These results support that neutrophil functional heterogeneity within the atherosclerotic lesions alters lesion stability. Specific targeting thereof may improve plaque stability without impacting host defense.
We present an optimized Sandell-Kolthoff (SK) spectrophotometric method for urinary iodine quantification, developed to enhance analytical accuracy, robustness, and suitability for high-throughput applications while minimizing reagent consumption. A stepwise refinement of an established protocol (Mod 1-4) was performed by adjusting reagent volumes, digestion temperature, and reaction conditions. The final optimized method (Mod 4) demonstrated excellent calibration linearity (r 2 = 0.99964) with a limit of quantification of 10.32 μg/L. Recovery rates for quality controls and certified reference materials ranged from 90 to 105%, with total imprecision (CVtotal) < 3% and analytical bias < 5%. Method comparison with inductively coupled plasma mass spectrometry (ICP-MS) and the Robert Koch Institute (RKI) reference method using Passing-Bablok regression and Bland-Altman analysis confirmed high concordance. Stability testing indicated that iodine concentrations remained unchanged during short-term storage at 4 °C, whereas repeated freeze-thaw cycles caused an average 16% decrease in measured concentrations. Surface contact with urine dipsticks introduced substantial exogenous iodine contamination, resulting in measurement overestimations of up to 45-fold. The optimized SK method provides a validated, precise, and resource-efficient approach for large-scale urinary iodine monitoring, aligning with World Health Organization (WHO) recommendations and addressing key limitations of existing colorimetric protocols.
Die strukturierte Patientenaufklärung stellt einen zentralen Bestandteil der perioperativen Versorgung dar und beeinflusst nachweislich Angst, Verständnis sowie Zufriedenheit von PatientInnen und deren Angehörigen. Insbesondere in der Herzchirurgie und in der Behandlung angeborener Herzfehler sind anatomische und prozedurale Zusammenhänge komplex und für Laien häufig schwer nachvollziehbar. In den letzten Jahren wurden additive Fertigung und digitale Technologien, wie beispielsweise Virtual Reality (VR), als innovative Instrumente zur Optimierung der Patientenaufklärung untersucht. Die vorliegende Übersicht fasst primär die Ergebnisse zweier eigens durchgeführter prospektiver randomisierter Studien zusammen, die den Einsatz von 3D-gedruckten Modellen und Virtual-Reality-Anwendungen in der Aufklärung von Erwachsenen sowie Eltern von Kindern mit angeborenen Herzfehlern evaluiert. Beide Arbeiten zeigen eine signifikante Verbesserung des prozeduralen Verständnisses durch den Einsatz dreidimensionaler Visualisierungsmethoden im Vergleich zu konventionellen papierbasierten Aufklärungsformaten. Darüber hinaus konnte insbesondere für VR-gestützte Aufklärung bei erwachsenen herzchirurgischen PatientInnen eine signifikante Reduktion der präoperativen Angst nachgewiesen werden. Bei Eltern von Kindern mit angeborenen Herzfehlern führte der Einsatz von 3D-gedruckten Modellen ebenfalls zu einer Reduktion der Angst sowie zu einer hohen Akzeptanz und Zufriedenheit. Die Ergebnisse unterstreichen das Potenzial von 3D-Druck und VR als ergänzende Werkzeuge zur patientenzentrierten, verständnisorientierten Aufklärung und liefern eine evidenzbasierte Grundlage für deren Integration in die klinische Routine.
BACKGROUND:Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscularization in patients with heart failure and a reduced left ventricular ejection fraction. METHODS:We conducted an open-label, phase 1-2 study of tissue-engineered heart repair by means of BioVAT transplantation. Patients with heart failure and a left ventricular ejection fraction of 35% or less and at least one hypokinetic or dyskinetic left ventricular segment were treated with BioVAT allografts, which consisted of 5, 10, or 20 engineered-heart-muscle units. All the patients received immunosuppression. Safety was assessed as adverse events related to the procedure. The primary efficacy end points were the change from baseline in the target heart-wall thickness, the left ventricular ejection fraction, and the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OSS). RESULTS:A total of 20 patients were treated in the study. Three patients died during the study (1 each from vasoplegia, coronavirus disease 2019, and aortic dissection). One patient underwent heart transplantation. Immunosuppression was discontinued in 4 patients because of implantation of a left ventricular assist device (in 2 patients), renal failure (in 1 patient), and urothelial carcinoma (in 1 patient). Of the 16 patients who were treated with the safe maximal dose (20 engineered-heart-muscle units), 12 patients completed the prespecified 3-month interim follow-up. The least-squares mean increase in the target-wall thickness was 4.5 mm (90% confidence interval [CI], 3.7 to 5.4; P<0.001), the increase in the left ventricular ejection fraction was 3.9 percentage points (90% CI, 0.9 to 6.8; P = 0.04), and the increase in the KCCQ-OSS was 6.7 points (90% CI, 1.0 to 12.5; P = 0.06). All the patients had at least one adverse event. CONCLUSIONS:In this interim analysis, cardiac remuscularization with BioVAT was associated with an increase in the target heart-wall thickness, left ventricular ejection fraction, and KCCQ-OSS at 3 months; all the patients had at least one adverse event. Longer-term follow-up and further clinical investigation are warranted. (Funded by the German Center for Cardiovascular Research and Repairon; BioVAT-HF ClinicalTrials.gov number, NCT04396899.).
