El shock cardiogénico como problema de salud. Fisiología, clasificación y detección / Cardiogenic shock as a health issue: Physiology, classification, and detection

El shock cardiogénico (SC) es un síndrome heterogéneo con elevada mortalidad y creciente incidencia. Se trata de una situación en la que existe un desequilibrio entre las necesidades tisulares de oxígeno y la capacidad del sistema cardiovascular para satisfacerlas debido a una disfunción cardiaca aguda. Históricamente, los síndromes coronarios agudos han sido la causa principal de SC; sin embargo, los casos no isquémicos han aumentado en incidencia. Su fisiopatología implica el daño isquémico del miocardio, una respuesta tanto simpática como del sistema renina-angiotensina-aldosterona e inflamatoria, que perpetúan la situación de hipoperfusión tisular conduciendo finalmente a la disfunción multiorgánica. La caracterización de los pacientes con SC mediante una valoración triaxial y la universalización de la escala SCAI ha permitido una estandarización de la estratificación de la gravedad del SC que, sumada a la detección precoz y el enfoque Hub and Spoke, podrían contribuir a mejorar el pronóstico de los pacientes en SC. (AU)

Cardiogenic shock (CS) is a heterogeneous syndrome with high mortality and increasing incidence. It is a condition where there is an imbalance between tissue oxygen demands and the cardiovascular system's capacity to meet them due to acute cardiac dysfunction. Historically, acute coronary syndromes have been the primary cause of CS; however, non-ischemic cases have seen a rise in incidence. Its pathophysiology involves myocardial ischemic damage, a sympathetic, renin–angiotensin–aldosterone system, and inflammatory response, perpetuating the situation of tissue hypoperfusion, ultimately leading to multiorgan dysfunction. Characterizing CS patients through a triaxial assessment and the widespread use of the SCAI scale has allowed standardization of CS severity stratification, which, coupled with early detection and the “Hub and Spoke” approach, could contribute to improve the prognosis of CS patients. (AU)

Cardiogenic shock as a health issue. Physiology, classification, and detection.

Cardiogenic shock (CS) is a heterogeneous syndrome with high mortality and a growing incidence. It is characterized by an imbalance between the tissue oxygen demands and the capacity of the cardiovascular system to meet these demands, due to acute cardiac dysfunction. Historically, acute coronary syndromes have been the primary cause of CS. However, non-ischemic cases have seen a rise in incidence. The pathophysiology involves ischemic damage of the myocardium and a sympathetic, renin-angiotensin-aldosterone system and inflammatory response, perpetuating the situation of tissue hypoperfusion and ultimately leading to multiorgan dysfunction. The characterization of CS patients through a triaxial assessment and the widespread use of the Society for Cardiovascular Angiography and Interventions (SCAI) scale has allowed standardization of the severity stratification of CS; this, coupled with early detection and the "hub and spoke" approach, could contribute to improving the prognosis of these patients.

Ecografía en el postoperatorio de cirugía cardíaca / Ultrasound use after cardiac surgery

La complejidad de los procedimientos quirúrgicos, así como la comorbilidad de los pacientes sometidos a cirugía cardiaca, van en aumento. La detección y el tratamiento precoz de las complicaciones posquirúrgicas son parte del éxito en la reducción de la morbimortalidad. La introducción de la técnica ecográfica ha sido fundamental en la valoración cardiopulmonar, hemodinámica y etiológica del paciente crítico, aportando información inmediata, fiable y a veces concluyente, permitiendo aclarar muchas situaciones clínicas sin respuesta terapéutica aceptable, por lo que se trata de una herramienta diagnóstica esencial. En este capítulo nos centraremos, fundamentalmente, en la valoración funcional y hemodinámica, y en la detección de las complicaciones cardiológicas más frecuentes en el postoperatorio de cirugía cardiaca. (AU)

Surgical complexity as well as comorbidities in patients undergoing cardiac surgery is increasing. Early detection and management of post-surgical complications are key points to reduce morbidity and mortality. Ultrasound technique plays a main rol in cardiopulmonary, hemodynamic and etiological assessment of the critically ill, providing immediate, reliable and, sometimes, conclusive information, clarifying many clinical situations with an inappropriate therapeutic response. For all these reasons ultrasound is an essential diagnostic tool. In this chapter we will focus, mainly, on functional and hemodynamic assessment and on the detection of most common cardiological complications in the postoperative period after cardiac surgery. (AU)

Manejo clínico del shock poscardiotomía en pacientes adultos / Clinical management of postcardiotomy shock in adults

Postcardiotomy cardiogenic shock represents the most serious expression of low cardiac output syndrome after cardiac surgery. Although infrequent, it is a relevant condition due to its specific and complex pathophysiology and important morbidity-mortality. The diagnosis requires a high index of suspicion and multimodal hemodynamic monitoring, where echocardiography and the pulmonary arterial catheter play a main role. Early and multidisciplinary management should focus on the management of postoperative or mechanical complications and the optimization of determinants of cardiac output through fluid therapy or diuretic treatments, inotropic drugs and vasopressors/vasodilators and, in the absence of a response, early mechanical circulatory support. The aim of this paper is to review and update the pathophysiology, diagnosis and management of postcardiotomy cardiogenic shock (AU)

El shock cardiogénico poscardiotomía representa la situación clínica más grave del síndrome de bajo gasto poscirugía cardiaca. Aunque infrecuente, su fisiopatología específica y compleja y su elevada morbimortalidad lo convierten en una entidad especialmente relevante en el contexto de la medicina intensiva. El diagnóstico requiere un elevado índice de sospecha clínica y monitorización multimodal, con un papel fundamental para la ecocardiografía y el catéter de arteria pulmonar. Su manejo debe ser precoz, escalonado y dinámico, multisistémico, multidisciplinar, basado en resolver potenciales complicaciones mecánicas y optimizar los determinantes del gasto cardiaco mediante aporte de volumen o tratamiento deplectivo, fármacos inotrópicos y vasopresores/vasodilatadores y, en ausencia de respuesta, soporte circulatorio mecánico precoz. El objetivo de este artículo es presentar una revisión narrativa y una actualización de la fisiopatología, el diagnóstico y el manejo clínico del shock poscardiotomía. Además, se proponen pautas de actuación que faciliten el manejo clínico diario (AU)

Clinical management of postcardiotomy shock in adults.

Postcardiotomy cardiogenic shock represents the most serious expression of low cardiac output syndrome after cardiac surgery. Although infrequent, it is a relevant condition due to its specific and complex pathophysiology and important morbidity-mortality. The diagnosis requires a high index of suspicion and multimodal hemodynamic monitoring, where echocardiography and the pulmonary arterial catheter play a main role. Early and multidisciplinary management should focus on the management of postoperative or mechanical complications and the optimization of determinants of cardiac output through fluid therapy or diuretic treatments, inotropic drugs and vasopressors/vasodilators and, in the absence of a response, early mechanical circulatory support. The aim of this paper is to review and update the pathophysiology, diagnosis and management of postcardiotomy cardiogenic shock.

[Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units]. / Recomendaciones para el manejo de los pacientes críticos con COVID-19 en las Unidades de Cuidados Intensivos.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Recommendations for the management of critically ill patients with COVID-19 in Intensive Care Units.

The COVID-19 pandemic has led to the admission of a high number of patients to the ICU, generally due to severe respiratory failure. Since the appearance of the first cases of SARS-CoV-2 infection, at the end of 2019, in China, a huge number of treatment recommendations for this entity have been published, not always supported by sufficient scientific evidence or with methodological rigor necessary. Thanks to the efforts of different groups of researchers, we currently have the results of clinical trials, and other types of studies, of higher quality. We consider it necessary to create a document that includes recommendations that collect this evidence regarding the diagnosis and treatment of COVID-19, but also aspects that other guidelines have not considered and that we consider essential in the management of critical patients with COVID-19. For this, a drafting committee has been created, made up of members of the SEMICYUC Working Groups more directly related to different specific aspects of the management of these patients.

Perioperative management in cardiovascular surgery. / Manejo perioperatorio en cirugía cardiovascular.

Cardio-surgical patient care requires a comprehensive and multidisciplinary approach to develop strategies to improve patient safety and outcomes. In the preoperative period, prophylaxis for frequent postoperative complications, such as de novo atrial fibrillation or bleeding, and prehabilitation based on exercise training, respiratory physiotherapy and nutritional and cognitive therapy, especially in fragile patients, stand out. There have been great advances, during the intraoperative phase, such as minimally invasive surgery, improved myocardial preservation, enhanced systemic perfusion and brain protection during extracorporeal circulation, or implementation of Safe Surgery protocols. Postoperative care should include goal-directed hemodynamic theraphy, a correct approach to coagulation disorders, and a multimodal analgesic protocol to facilitate early extubation and mobilization. Finally, optimal management of postoperative complications is key, including arrhythmias, vasoplegia, bleeding, and myocardial stunning that can lead to low cardiac output syndrome or, in extreme cases, cardiogenic shock. This global approach and the high degree of complexity require highly specialised units where intensive care specialists add value and are key to obtain more effective and efficient clinical results.

ARIAM, 25 años salvando corazones / ARIAM, 25 years saving hearts

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Índice de cardioplejía infundida: una nueva herramienta en la protección miocárdica. Un estudio de cohortes / Infused cardioplegia index: A new tool to improve myocardial protection. A cohort study

Objetivo: La cardioprotección es esencial en la revascularización coronaria quirúrgica. En este estudio exploramos la relación existente entre el tiempo que una masa miocárdica permanece en situación de isquemia y la dosis de cardioplejía utilizada para su preservación, reflejada a través del índice de cardioplejía infundida, con el desarrollo de bajo gasto cardiaco postoperatorio. Diseño: Se incluyeron todos los pacientes sometidos a revascularización coronaria quirúrgica entre enero de 2013 y diciembre de 2015. El síndrome de bajo gasto cardiaco postoperatorio se definió siguiendo los criterios del documento de consenso de la SEMYCIUC. Se analizaron los factores perioperatorios asociados al síndrome de bajo gasto cardiaco y, mediante la curva ROC, se determinó el punto de corte del índice de cardioplejía infundida para predecir la ausencia del mismo. Resultados: De los 360 pacientes incluidos, 116 (32%) presentaron bajo gasto postoperatorio. Los factores de riesgo independientes fueron: clasificación funcional de la New York Heart Association (OR 1,8 [IC 95%=1,18-2,55]), la fracción de eyección del ventrículo izquierdo (OR 0,95 [IC 95%=0,93-0,98]), el empleo de cardioplejía retrógrada (OR 1,2 [IC 95%=1,03-1,50]) y el índice de cardioplejía infundida (OR 0,99 [IC 95%=0,991-0,996]), que mostró un área bajo la curva ROC de 0,77 (0,70-0,83; p<0,001) para la ausencia de síndrome de bajo gasto cardiaco postoperatorio, usando como punto de corte óptimo 23,6ml·min-1(100g/m2 de VI)-1. Conclusiones: El índice de cardioplejía infundido es inversamente proporcional a los requerimientos postoperatorios de inotropos, pudiendo constituir una estrategia para optimizar la cardioprotección. El volumen total de cardioplejía intermitente debería calcularse, de forma individualizada, en base al índice de masa del ventrículo izquierdo y el tiempo de isquemia

Background: Strategies for cardio-protection are essential in coronary artery bypass graft surgery. The authors explored the relationship between cardioplegia volume, left ventricular mass index and ischemia time by means of the infused cardioplegia index and its relationship with post-operative low cardiac output syndrome. Design: All patients undergoing coronary artery bypass graft surgery between January 2013 and December 2015 were included. Low cardiac output syndrome was defined according to criteria of the SEMICYUC's consensus document. The perioperative factors associated with low cardiac output syndrome were estimated, and using a ROC curve, the optimum cut-off point for the infused cardioplegia index to predict the absence of low cardiac output syndrome was calculated. Results: Of 360 patients included, 116 (32%) developed low cardiac output syndrome. The independent risk predictors were: New York Heart Association Functional Classification (OR 1.8 [95% CI=1.18-2.55]), left ventricle ejection fraction (OR 0.95 (95% CI=0.93-0.98]), ICI (OR 0.99 [95% CI=0.991-0.996]) and retrograde cardioplegia (OR 1.2 [95% CI=1.03-1.50]). The infused cardioplegia index showed an area under the ROC curve of 0.77 (0.70-0.83; P<.001) for the absence of postoperative low cardiac output syndrome using the optimum cut-off point of 23.6ml·min-1(100g/m2 of LV)-1. Conclusions: The infused cardioplegia index presents an inverse relationship with the development of post-operative low cardiac output syndrome. This index could form part of new strategies aimed at optimising cardio-protection. The total volume of intermittent cardioplegia, especially that of maintenance, should probably be individualised, adjusting for ischemia time and left ventricle mass index

Infused cardioplegia index: A new tool to improve myocardial protection. A cohort study. / Índice de cardioplejía infundida: una nueva herramienta en la protección miocárdica. Un estudio de cohortes.

BACKGROUND: Strategies for cardio-protection are essential in coronary artery bypass graft surgery. The authors explored the relationship between cardioplegia volume, left ventricular mass index and ischemia time by means of the infused cardioplegia index and its relationship with post-operative low cardiac output syndrome. DESIGN: All patients undergoing coronary artery bypass graft surgery between January 2013 and December 2015 were included. Low cardiac output syndrome was defined according to criteria of the SEMICYUC's consensus document. The perioperative factors associated with low cardiac output syndrome were estimated, and using a ROC curve, the optimum cut-off point for the infused cardioplegia index to predict the absence of low cardiac output syndrome was calculated. RESULTS: Of 360 patients included, 116 (32%) developed low cardiac output syndrome. The independent risk predictors were: New York Heart Association Functional Classification (OR 1.8 [95% CI=1.18-2.55]), left ventricle ejection fraction (OR 0.95 (95% CI=0.93-0.98]), ICI (OR 0.99 [95% CI=0.991-0.996]) and retrograde cardioplegia (OR 1.2 [95% CI=1.03-1.50]). The infused cardioplegia index showed an area under the ROC curve of 0.77 (0.70-0.83; P<.001) for the absence of postoperative low cardiac output syndrome using the optimum cut-off point of 23.6ml·min-1(100g/m2 of LV)-1. CONCLUSIONS: The infused cardioplegia index presents an inverse relationship with the development of post-operative low cardiac output syndrome. This index could form part of new strategies aimed at optimising cardio-protection. The total volume of intermittent cardioplegia, especially that of maintenance, should probably be individualised, adjusting for ischemia time and left ventricle mass index.

Cardiac troponins: 25 years on the stage and still improving their clinical value.

Twenty-five years ago, non-isotopic immunoassays for measuring the cardiac specific isoforms of troponin I (cTnI) and T (cTnT) were developed. Both biomarkers radically changed the diagnosis, prognosis, and therapy indication of acute coronary syndromes (ACS) and, particularly, of myocardial infarction (MI). However, cardiac troponins (cTn) rapidly demonstrated their usefulness in other cardiac and non-cardiac conditions, a part of the ischemic coronary diseases. Consequently, the number of patients to be tested for cTn and the number of tests requested to clinical laboratories sharply increased. Though the manufacturers continuously improved the analytical characteristics of the first cTn assays and produced different cTn assay "generations", the universal definition of myocardial infarction required less-than-available analytical imprecision at the cTn concentration used to assess MI (i.e. the 99th reference percentile). To address the clinical requirements, manufacturers developed the high-sensitivity cTn (hs-cTn) assays that allow to measure the 99th reference percentile with adequate precision, to detect cTn in many healthy subjects and, hence, to calculate the hs-cTn biological variation and especially to observe in very short time intervals serial differences in hs-cTn attributable to cardiac ischemia. Since the number of patients attending the emergency departments (ED) for a suspected ACS or MI is increasing, the improved properties of hs-cTn assays, allowing faster and safer patient assessment, will help to alleviate the sometimes overcrowded EDs. However, there are many biological, analytical, and clinical factors that can influence the true hs-cTn values of a patient. Clinicians and laboratory professionals should know about them for the best interpretation of the otherwise largely useful hs-cTn measurements. In conclusion, 25 years after their introduction for clinical use, "cTn are still on the stage and improving their clinical value".

Serial Sampling of High-Sensitivity Cardiac Troponin T May Not Be Required for Prediction of Acute Myocardial Infarction Diagnosis in Chest Pain Patients with Highly Abnormal Concentrations at Presentation.

BACKGROUND: Guidelines for diagnosing acute myocardial infarction (AMI) recommend adding kinetic changes to the initial cardiac troponin (cTn) blood concentration to improve AMI diagnosis. We hypothesized that kinetic changes may not be required in patients presenting with highly abnormal cTn. METHODS: Patients presenting with suspected AMI to the emergency department were enrolled in a prospective diagnostic study. We assessed the positive predictive value (PPV) of initial high-sensitivity cardiac troponin T (hs-cTnT) blood concentrations alone and in combination with kinetic changes for AMI. Predefined relative changes (δ change of ≥20%) and absolute changes (Δ change ≥9.2 ng/L) within different time intervals (1 h, 2 h, and 4-14 h after presentation) were assessed. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: Among 1282 patients, 213 (16.6%) patients had a final diagnosis of AMI. For AMI prediction, PPVs increased from 48.8% for an initial hs-cTnT >14 ng/L to 87.2% for >60 ng/L, whereas PPVs remained unchanged for higher hs-cTnT concentrations at baseline (87.1% for both >80 ng/L and >100 ng/L). With addition of 20% relative Δ change, PPVs were not further improved in patients with baseline hs-cTnT >80 ng/L using the 1-h (84.0%) and 2-h (88.9%) intervals, and only minimally when extending the interval to 4-14 h (91.2% for >80 ng/L and 90.4% for >100 ng/L, respectively). Similar findings were observed when applying absolute changes. CONCLUSIONS: In chest pain patients with highly abnormal hs-cTnT concentrations at presentation, subsequent blood draws may not be required, as they do not provide incremental diagnostic value for prediction of AMI diagnosis.

The Use of Very Low Concentrations of High-sensitivity Troponin T to Rule Out Acute Myocardial Infarction Using a Single Blood Test.

BACKGROUND: Recent single-center and retrospective studies suggest that acute myocardial infarction (AMI) could be immediately excluded without serial sampling in patients with initial high-sensitivity cardiac troponin T (hs-cTnT) levels below the limit of detection (LoD) of the assay and no electrocardiogram (ECG) ischemia. OBJECTIVE: We aimed to determine the external validity of those findings in a multicenter study at 12 sites in nine countries. METHODS: TRAPID-AMI was a prospective diagnostic cohort study including patients with suspected cardiac chest pain within 6 hours of peak symptoms. Blood drawn on arrival was centrally tested for hs-cTnT (Roche; 99th percentile = 14 ng/L, LoD = 5 ng/L). All patients underwent serial troponin sampling over 4-14 hours. The primary outcome, prevalent AMI, was adjudicated based on sensitive troponin I (Siemens Ultra) levels. Major adverse cardiac events (MACE) including AMI, death, or rehospitalization for acute coronary syndrome with coronary revascularization were determined after 30 days. RESULTS: We included 1,282 patients, of whom 213 (16.6%) had AMI and 231 (18.0%) developed MACE. Of 560 (43.7%) patients with initial hs-cTnT levels below the LoD, four (0.7%) had AMI. In total, 471 (36.7%) patients had both initial hs-cTnT levels below the LoD and no ECG ischemia. These patients had a 0.4% (n = 2) probability of AMI, giving 99.1% (95% confidence interval [CI] = 96.7% to 99.9%) sensitivity and 99.6% (95% CI = 98.5% to 100.0%) negative predictive value. The incidence of MACE in this group was 1.3% (95% CI = 0.5% to 2.8%). CONCLUSIONS: In the absence of ECG ischemia, the detection of very low concentrations of hs-cTnT at admission seems to allow rapid, safe exclusion of AMI in one-third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.

Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T.

STUDY OBJECTIVE: We aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction. METHODS: We enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT below 12 ng/L and Δ1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L or Δ1 hour at least 5 ng/L to rule in; remaining patients to the "observational zone") was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT. RESULTS: Among 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone. CONCLUSION: The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.

HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism.

The monocyte-macrophage lineage shows a high degree of diversity and plasticity. Once they infiltrate tissues, they may acquire two main functional phenotypes, being known as the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by bacterial products and interferon-γ and exerts a cytotoxic effect on cancer cells. Conversely, the alternatively activated M2 phenotype is induced by Il-4/IL13 and promotes tumor cell growth and vascularization. Although receptor for advanced glycation end-products (RAGE) engagement in M1 macrophages has been reported by several groups to promote inflammation, nothing is known about the functionality of RAGE in M2 macrophages. In the current study, we demonstrate that RAGE is equally expressed in both macrophage phenotypes and that RAGE activation by high-mobility group protein box1 (HMGB1) promotes protumoral activities of M2 macrophages. MKN45 cells co-cultured with M2 macrophages treated with HMGB1 at different times displayed higher invasive abilities. Additionally, conditioned medium from HMGB1-treated M2 macrophages promotes angiogenesis in vitro. RAGE-targeting knockdown abrogates these activities. Overall, the present findings suggest that HMGB1 may contribute, by a RAGE-dependent mechanism, to the protumoral activities of the M2 phenotype.

Valor predictivo de la troponina T de alta sensibilidad para descartar el rechazo agudo tras un trasplante cardiaco / Predictive Value of High-sensitive Troponin T to Rule Out Acute Rejection After Heart Transplantation

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Evidence of involvement of the receptor for advanced glycation end-products (RAGE) in the adhesion of Helicobacter pylori to gastric epithelial cells.

The adherence of Helicobacter pylori to gastric epithelial cells is required for prolonged persistence in the stomach and for induction of injury. Here, we first reported a new role of the receptor for advanced glycation end-products (RAGE) on the adherence of H. pylori to gastric epithelial cells, assessed by different methods and binding to immobilized RAGE. RAGE-targeted knock-down in MKN74 cell line markedly reduced not only the adhesion of H. pylori, but also the levels of IL-8 transcripts and protein released in response to infection. These data suggest that RAGE may represent a new factor on the pathogenesis of H. pylori infection.