Remodelling of the extracellular matrix (ECM) and cell surface by matrix metalloproteinases (MMPs) is an important function of monocytes and macrophages. Recent work has emphasised the diverse roles ...of classically and alternatively activated macrophages but the consequent regulation of MMPs and their inhibitors has not been studied comprehensively. Classical activation of macrophages derived in vitro from un-fractionated CD16(+/-) or negatively-selected CD16(-) macrophages up-regulated MMP-1, -3, -7, -10, -12, -14 and -25 and decreased TIMP-3 steady-state mRNA levels. Bacterial lipopolysaccharide, IL-1 and TNFα were more effective than interferonγ except for the effects on MMP-25, and TIMP-3. By contrast, alternative activation decreased MMP-2, -8 and -19 but increased MMP -11, -12, -25 and TIMP-3 steady-state mRNA levels. Up-regulation of MMPs during classical activation depended on mitogen activated protein kinases, phosphoinositide-3-kinase and inhibitor of κB kinase-2. Effects of interferonγ depended on janus kinase-2. Where investigated, similar effects were seen on protein concentrations and collagenase activity. Moreover, activity of MMP-1 and -10 co-localised with markers of classical activation in human atherosclerotic plaques in vivo. In conclusion, classical macrophage activation selectively up-regulates several MMPs in vitro and in vivo and down-regulates TIMP-3, whereas alternative activation up-regulates a distinct group of MMPs and TIMP-3. The signalling pathways defined here suggest targets for selective modulation of MMP activity.
BACKGROUND—The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain ...to be elucidated.
METHODS AND RESULTS—We compared 35 athletes (80% men, age14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls.
CONCLUSIONS—Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography.
A 52‐year‐old male with no history of familiar sudden death arrived at our Emergency Department after syncope with loss of consciousness occurred during high fever. The thoracic high‐resolution ...computed tomography demonstrated bilateral multiple ground‐glass opacities. The nose‐pharyngeal swab resulted positive for SARS‐CoV‐2. The 12‐lead ECG presented a “coved‐type” aspect in leads V1 and V2 at the fourth intercostal space and a first degree atrio‐ventricular block. As soon as the temperature went down, the 12‐lead ECG resumed a normal aspect, maintaining a long PR interval.
A 52‐year‐old male with no history of familiar sudden death arrived at our Emergency Department after syncope with loss of consciousness occurred during high fever. The thoracic high‐resolution computed tomography demonstrated bilateral multiple ground‐glass opacities. The nose‐pharyngeal swab resulted positive for SARS‐CoV‐2. The 12‐lead ECG presented a “coved‐type” aspect in leads V1 and V2 at the fourth intercostal space and a first degree atrio‐ventricular block. As soon as the temperature went down, the 12‐lead ECG resumed a normal aspect, maintaining a long PR interval.
Background The new designation of arrhythmogenic cardiomyopathy defines a broader spectrum of disease phenotypes, which include right dominant, biventricular, and left dominant variants. We evaluated ...the relationship between electrocardiographic findings and contrast-enhanced cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy. Methods and Results We studied a consecutive cohort of patients with a definite diagnosis of arrhythmogenic cardiomyopathy, according to 2010 International Task Force criteria, who underwent electrocardiography and contrast-enhanced cardiac magnetic resonance. Both depolarization and repolarization electrocardiographic abnormalities were correlated with the severity of dilatation/dysfunction, either global or regional, of both ventricles and the presence and regional distribution of late gadolinium enhancement. The study population included 79 patients (60% men). There was a statistically significant relationship between the presence and extent of T-wave inversion across a 12-lead ECG and increasing values of median right ventricular ( RV ) end-diastolic volume ( P<0.001) and decreasing values of RV ejection fraction ( P<0.001). The extent of T-wave inversion to lateral leads predicted a more severe RV dilatation rather than a left ventricular involvement because of the leftward displacement of the dilated RV , as evidenced by contrast-enhanced cardiac magnetic resonance. A terminal activation delay of >55 ms in the right precordial leads (V1-V3) was associated with higher RV volume ( P=0.014) and lower RV ejection fraction ( P=0.053). Low QRS voltages in limb leads predicted the presence ( P=0.004) and amount ( P<0.001) of left ventricular late gadolinium enhancement. Conclusions The study results indicated that electrocardiographic abnormalities predict the arrhythmogenic cardiomyopathy phenotype in terms of severity of RV disease and left ventricular involvement, which are among the most important determinants of the disease outcome.
RESUMEN Introducción: La calidad de vida relacionada con la salud medida a través de los “resultados reportados por pacientes”, del inglés: patient reported outcomes (PROs) permite la detección ...efectiva de problemas físicos y psicológicos en pacientes con hepatitis crónica. Objetivo: Describir las dimensiones de calidad de vida más afectadas reportados por pacientes con infección crónica por virus de la Hepatitis C y B. Material y Métodos: Se realizó un estudio descriptivo, transversal desde junio 2018 hasta diciembre 2020 en el Instituto de Gastroenterología (IGE). Entre 1 706 pacientes con diagnóstico VHB y VHC atendidos, la muestra quedó constituida por 366 adultos con infección crónica por los virus de hepatitis B (VHB) y C (VHC). Se registraron los resultados de las encuestas: Evaluación Funcional para el Tratamiento de Enfermedades Crónicas -Fatiga (FACIT-F) y Cuestionario de Impedimento de la Productividad y Actividad Laboral- Problema de salud específico (WPAI-SPH) y parámetros clínico-demográficos. Resultados: Se identificaron 271 (74,0 %) pacientes con diagnóstico de VHC y 95 (26,0 %) de VHB, con edad media 54,0 ± 12,7 años, 209 (57,1 %) mujeres. La puntuación total de la FACIT-F estuvo más afectada en VHC (FACIT-F: HVB: 129,0 ± 15,9 vs. VHC: 111,2 ± 23,5; p<0,0001), quienes a su vez tuvieron mayor deterioro de la actividad laboral (WPAI-SPH: VHB: 0,309 ± 0,312 vs. VHC: 0,386 ± 0,333; p<0,05). Conclusiones: Los pacientes con VHC vivencian una peor calidad de vida que compromete su bienestar, rendimiento laboral y cotidiano.
Pocket hematoma is a common complication of cardiac implantable electronic device (CIED) procedures. the aim of the study was to research the clinical factors associated with pocket hematoma ...formation after CIED implantation or replacement and to identify the best perioperative antithrombotic management.
We retrospectively analyzed 500 consecutive patients who underwent to CIED implantation or replacement at our center from November 2014.
Among our population, 206 patients (41.2%) were on anticoagulant therapy at the time of the intervention: 68 (13.6%) on ongoing Warfarin; 111 (22.2%) on low-molecular-weight heparin (LMWH); and 27 (5.4%) on ongoing direct oral anticoagulants. Antiplatelet therapy was present in 262 (52.4%) patients: in particular, 50 (10%) were on dual antiplatelet therapy, 64 (12.8%) were on single antiplatelet therapy and anticoagulant therapy, whereas 12 (2.4%) were on anticoagulant with dual antiplatelet therapy.Incidence of pocket hematoma after CIEDs implantation was of 4.6%. Considering the different perioperative anticoagulant strategies, patients on LMWH presented the higher hematoma rate 11/100 patients (11.0%), P < 0.001. At the multivariate analysis, anticoagulant with dual antiplatelet therapy (P = 0.021, OR 6.3, IC 1.3-30.8), left ventricular ejection fraction (LVEF) less than 30% (P < 0.001, OR 7.4, IC 2.7-20.4), and use of LMWH (P = 0.008, OR 3.8, IC 1.4-10.6) resulted the strongest predictors of pocket hematoma (Hosmer test = 0.899).Considering replacement procedures, incidence of pocket hematoma was of 4.4%. The incidence was higher after ICD/CRT-D replacement. The majority of pocket hematoma occurred in patients with mechanical valve prosthesis (3/4 cases, 75%, P < 0.001).
The use of LMWH and a low LVEF expose patients to a higher risk of pocket hematoma after CIED procedures. Anticoagulant with dual antiplatelet therapy and LMWH should be avoided.
Introducción: el benceno es un hidrocarburo aromático obtenido por destilación del alquitrán utilizado en gasolineras y como solvente industrial, clasificado como cancerígeno por exposición ...ocupacional o ambiental. Está relacionado con el desarrollo de leucemia mieloide aguda (LMA) por su absorción principal por vía inhalatoria, y su metabolismo hepático con producción de benzoquinona de alta liposolubilidad que le permite depositarse en la médula ósea y tejido graso. Objetivo: analizar la asociación de las formas de exposición por actividades económicas, oficios, cargos, exposición ambiental y aditiva con el desarrollo de LMA. Materiales y métodos: revisión sistemática de la literatura en las bases de datos Medline, Embase, Lilacs, Cochrane Library, Toxnet y OpenGrey, en inglés y español con los términos benzene, cancer, leukemia, occupational and enviromental exposition. Resultados: la mayoría de los estudios muestran una relación causal entre la exposición a benceno y el desarrollo de LMA, con predominio en ambientes laborales, seguidos de factores ambientales y aditivos como el humo del cigarrillo. Conclusiones: se encontró evidencia de asociación entre la exposición a benceno ocupacional y/o ambiental con el desarrollo de leucemia mieloide aguda, debido a que altera el estrés oxidativo y la desregulación del aryl hidrocarburo generando efectos citogenéticos, mutación genética y alteraciones epigenéticas que se expresan en hematotoxicidad y desarrollo de leucemia.
Abstract Background The pathophysiologic mechanisms and the prognostic meaning of electrocardiographic (ECG) T-wave inversion (TWI) occurring in a subgroup of patients with clinically suspected acute ...myocarditis remain to be elucidated. Contrast-enhanced cardiac magnetic resonance (CMR) offers the potential to identify myocardial tissue changes such as edema and/or fibrosis which may underlie TWI. Methods and results We studied 76 consecutive patients (median age 34 years) with clinically suspected acute myocarditis, using a comprehensive CMR protocol which included T2 weighted sequences for myocardial edema. At the time of CMR, TWI was observed in 21 (27%) patients. There was a statistically significant association of TWI with the median number of left ventricular (LV) segments showing both any pattern of myocardial edema (transmural and non-transmural) 5 (3-7) vs. 3 (2-4); p = 0.015 and myocardial late-gadolinium-enhancement 4 (3-7) vs. 3 (2-4); p = 0.002. Transmural myocardial edema involving ≥ 2 LV segments was found in 17/21 (81%) patients with TWI versus 13/55 (24%) patients without TWI ( p < 0.001) and remained the only independent predictor of TWI at multivariable analysis (OR = 9.96; 95%CI = 2.71–36.6; p = 0.001). Overall, topographic concordance between the location of TWI across the ECG leads and the regional distribution of transmural myocardial edema was 88%. There was no association between acute TWI and reduced LV ejection fraction (< 55%) at 6-months of follow-up. Conclusions This is the first study to demonstrate an association between LV transmural myocardial edema as evidenced by CMR sequences and TWI in clinically suspected acute myocarditis. As an expression of reversible myocardial edema, development of TWI during the acute disease phase was not a predictor of LV systolic dysfunction at follow-up.
In patients who survived out-of-hospital cardiac arrest (OHCA), it is crucial to establish the underlying cause and its potential reversibility.
The purpose of this study was to assess the ...incremental diagnostic and prognostic role of early cardiac magnetic resonance (CMR) in survivors of OHCA.
Among 139 consecutive OHCA patients, the study enrolled 44 patients (median age 43 years; 84% male) who underwent coronary angiography and CMR ≤7 days after admission. The CMR protocol included T2-weighted sequences for myocardial edema and late gadolinium enhancement (LGE) sequences for myocardial fibrosis.
Coronary angiography identified obstructive coronary artery disease in 18 of 44 patients in whom CMR confirmed the diagnosis of ischemic heart disease by demonstrating subendocardial or transmural LGE. The presence of myocardial edema allowed differentiation between acute myocardial ischemia (n = 12) and postinfarction myocardial scar (n = 6). Among the remaining 26 patients without obstructive coronary artery disease, CMR in 19 (73%) showed dilated cardiomyopathy in 5, myocarditis in 4, mitral valve prolapse associated with LGE in 3, ischemic scar in 2, idiopathic nonischemic scar in 2, arrhythmogenic cardiomyopathy in 1, hypertrophic cardiomyopathy in 1, and takotsubo cardiomyopathy in 1. In this subgroup of 26 patients, 6 (23%) had myocardial edema. During mean follow-up of 36 ± 17 months, all 18 patients with myocardial edema had an uneventful outcome, whereas 9 of 26 (35%) without myocardial edema experienced sudden arrhythmic death (n = 1), appropriate defibrillator interventions (n = 5), and nonarrhythmic death (n = 3; P = .006).
In survivors of OHCA, early CMR with a comprehensive tissue characterization protocol provided additional diagnostic and prognostic value. The identification of myocardial edema was associated with a favorable long-term outcome.
Abstract Objectives This study was conducted to examine the relationship between endogenous secretory receptors for advanced glycation end products (esRAGE) and oxidative stress in type 2 diabetic ...patients (T2DM) with/without advanced macro-angiopathy. Methods Sixty-one T2DM were assessed for glycemic control, lipid profile, AGEs, carboxymethyl-lysine (CML), soluble receptor for advanced glycation end products (sRAGE), esRAGE and vitamin E levels, and underwent echo-color-Doppler of the abdominal aorta and aorto-iliac tree, carotid and lower limb arteries to check for evidence of plaques. Results AGEs and CML levels were significantly higher in T2DM with plaques than in those without ( P = 0.0156 and P = 0.007, respectively) despite a comparable metabolic control and history of disease. EsRAGE and vitamin E levels were lower in T2DM with than in those without plaques ( P < 0.0001), while no differences were observed as regards sRAGE levels. Considering all T2DM, univariate regression analysis showed a positive correlation between esRAGE and vitamin E ( r = 0.456, P < 0.001), and a negative correlation between esRAGE and AGEs ( r = −0.284, P < 0.05). After dividing patients by the presence/absence of plaques, esRAGE only correlated directly with vitamin E ( r = 0.563, P < 0.01) and CML ( r = 0.479, P < 0.05) in patients without plaques. Conclusions This is the first study to establish a relationship between esRAGE and oxidative stress and/or antioxidant power, suggesting that esRAGE upregulation might be part of the cell's antioxidative defenses against plaque forming as a result of oxidative stress in the T2DM phenotype (cases with a more efficient esRAGE production being better protected).
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