ARGEN SHOCK: Mortality related to the use of Swan Ganz and to the hemodynamic pattern found in patients with AMICS.

The Swan Ganz Catheter (SGC) allows us to diagnose different types of cardiogenic shock (CS). OBJECTIVES: 1) Determine the frequency of use of SGC, 2) Analyze the clinical characteristics and mortality according to its use and 3) Analyze the prevalence, clinical characteristics and mortality according to the type of Shock. METHODS: The 114 patients (p) from the ARGEN SHOCK registry were analyzed. A "classic" pattern was defined as PCP > 15 mm Hg, CI < 2.2 L/min/ m2, SVR > 1,200 dynes × sec × cm-5. A "vasoplegic/mixed" pattern was defined when p did not meet the classic definition. CS due to right ventricle (RV) was excluded. RESULTS: SGC was used in 35 % (n:37). There were no differences in clinical characteristics according to SGC use, but those with SGC were more likely to receive dobutamine, levosimendan, and intra aortic balloon pump (IABP). Mortality was similar (59.4 % vs 61.3 %). The pattern was "classic" in 70.2 %. There were no differences in clinical characteristics according to the type of pattern or the drugs used. Mortality was 54 % in patients with the classic pattern and 73 % with the mixed/vasoplegic pattern, but the difference did not reach statistical significance (p:0.23). CONCLUSIONS: SGC is used in one third of patients with CS. Its use does not imply differences in the drugs used or in mortality. Most patients have a classic hemodynamic pattern. There are no differences in mortality or in the type of vasoactive agents used according to the CS pattern found.

Registro ARGEN-IAM-ST: infarto de miocardio con elevación del segmento ST en el "nuevo" adulto mayor / ARGEN-IAM-ST Registry: ST-elevation myocardial infarction in "new" older adults

RESUMEN Introducción: La Organización Mundial de la Salud (OMS) considera adulto mayor (AM) a las personas que tienen 60 años o más. Es sabido que la mortalidad por infarto agudo de miocardio (IAM) aumenta a edades más avanzadas, pero siempre se han utilizado umbrales de edad mayores que el propuesto por la OMS, por lo cual describir las características y evolución intrahospitalaria de este subgrupo (de acuerdo con la definición de la OMS) se torna relevante. Objetivos: 1) conocer la prevalencia de los AM según la OMS, con IAM con elevación del segmento ST en Argentina y 2) com- parar sus características, tratamientos de reperfusión y mortalidad con los adultos jóvenes. Material y métodos: Se analizaron los pacientes ingresados en el Registro Nacional de Infarto (ARGEN-IAM-ST). Se compara- ron las características clínicas, tratamientos y evolución de los AM y los adultos jóvenes. Resultados: Se incluyeron 6676 pacientes, de los cuales 3626 (54,3%) eran AM. Los AM fueron más frecuentemente mujeres (37,6% vs. 31,4%, p <0,001), hipertensos (67,8% vs. 47%, p <0,001), diabéticos (26,1% vs. 19,9%, p <0,001), dislipidémicos (45,4% vs. 37%, p <0,001), y tuvieron más antecedentes coronarios (16% vs. 10,3%, p <0,001). El tiempo a la consulta de los AM fue mayor (120 min vs. 105 min, p <0,001) con similar tiempo total de isquemia (314 min vs. 310 min, p = 0,33). Recibi- eron menos tratamiento de reperfusión (89,9% vs. 88,6%, p = 0,04) y más angioplastia primaria (91 % vs. 87,4%, p <0,001). Tuvieron más insuficiencia cardíaca (27,3% vs. 18,5%, p <0,001), similar incidencia de sangrado (3,7 vs. 3,1%, p = 0,33) y una mortalidad significativamente mayor (11,4% vs. 5,5%, p <0,001). Ser AM fue predictor independiente de mortalidad. Conclusiones: Más de la mitad de los IAM en nuestro país ocurren en AM. Los pacientes mayores tienen menor probabilidad de recibir reperfusión, más insuficiencia cardíaca y el doble de la mortalidad que los pacientes menores de 60 años.

ABSTRACT Background: The World Health Organization (WHO) defines an Older Adult (OA) as any individual aged 60 or older. It is known that mortality due to acute myocardial infarction (AMI) increases with age, but age thresholds higher than those proposed by the WHO have been consistently used; therefore, describing the characteristics and in-hospital progress of this subgroup of patients, in accordance with the WHO definition, becomes relevant. Objectives: 1) To know the prevalence of OA with acute ST-elevation myocardial infarction (STEMI) in Argentina according to the WHO, and 2) to compare their characteristics, reperfusion treatments, and mortality against those in young adults. Methods: Patients included in the National Registry of ST- Elevation Myocardial Infarction (Registro Nacional de Infarto con Elevación del ST, ARGEN-IAM-ST) were analyzed. Clinical features, therapies, and progress were compared in OA versus young adults. Results: A total of 6676 patients were enrolled, 3626 of which (54.3%) were OA. OA were mostly female (37.6% vs 31.4%, p <0.001), had hypertension (67.8% vs 47%, p <0.001), diabetes (26.1% vs 19.9%, p <0.001), dyslipidemia (45.4% vs 37%, p <0.001), and a longer coronary artery disease history (16% vs 10.3%, p < 0.001). The time to consultation in OA was longer (120 min vs 105 min, p <0.001), with a similar total ischemic time (314 min vs 310 min, p = 0.33). They received less reperfu- sion treatment (89.9% vs 88.6%, p = 0.04) and more primary angioplasty (91% vs 87.4%, p <0.001). Heart failure was more common in OAs (27.3% vs 18.5%, p <0.001), with a similar bleeding incidence (3.7% vs 3.1%, p = 0.33), and significantly higher mortality (11.4% vs 5.5%, p<0.001). Being an OA was an independent mortality predictor. Conclusions: More than half the cases of AMI in our country occur in OA. Older patients are less likely to receive reperfusion, more likely to have heart failure, and show twice the rate of mortality as compared to patients under 60.

Shock cardiogénico en el contexto de los síndromes coronarios agudos en Argentina: resultados del Registro ARGEN SHOCK 2 / Cardiogenic Shock in the Setting of Acute Coronary Syndromes in Argentina: Results from the ARGEN SHOCK 2 Registry

RESUMEN El shock cardiogénico (SC) es una complicación grave del infarto agudo de miocardio (IAM) y constituye una de sus principales causas de muerte. Objetivos: Conocer las características clínicas, estrategias de tratamiento, evolución intrahospitalaria y mortalidad a 30 días del SC en Argentina. Material y métodos: Se trata de un registro prospectivo, multicéntrico, de pacientes internados con SC en el contexto de los IAM con y sin elevación del segmento ST durante 14 meses (1 de agosto 2021 al 30 de septiembre 2022) en 23 centros de Argentina. Resultados: Se incluyeron 114 pacientes, edad 64 (58-73) años, 72% hombres. El 76,3% de los casos corresponden a IAM con elevación del segmento ST, 12,3% a IAM sin elevación del segmento ST, el 7% a infarto de ventrículo derecho y el 4,4% a complicaciones mecánicas. El SC estuvo presente desde el ingreso en el 66,6% de los casos. Revascularización: 91,1%, uso de inotrópicos: 98,2%, asistencia respiratoria mecánica: 59,6%, SwanGanz: 33,3%, balón de contrapulsación intraaórtico: 30,1%. La mortalidad intrahospitalaria global fue 60,5%, sin diferencias entre los IAM con o sin elevación del segmento ST, y a 30 días del 62,6%. Conclusiones: La morbimortalidad del SC es muy elevada a pesar de la alta tasa de reperfusión empleada.

ABSTRACT Background: Cardiogenic shock (CS) is a life-threatening complication of acute myocardial infarction (AMI) and constitutes one of the leading causes of death. Objective: The aim of this study was to investigate the clinical characteristics, treatment strategies, hospital outcome and 30-day mortality of CS in Argentina. Methods: We conducted a prospective, and multicenter registry of patients with acute myocardial infarction (AMI) with and without ST-segment elevation complicated with CS that were hospitalized in 23 centers in Argentina for 14 months (between August 1, 2021, and September 30, 2022). Results: The cohort was made up of 114 patients; median age was 64 years (58-73) and 72% were women; 76.3% corresponded to ST-segment elevation AMI, 12.3% to non-ST-segment elevation AMI, 7% had right ventricular infarction and 4.4% had mechanical complications. In 66.6% of cases CS was present on admission. Revascularization: 91.1%, use of inotropic agents: 98.2%, mechanical ventilation: 59.6%, Swan-Ganz catheter: 33.3%, intra-aortic balloon pump: 30.1%. Overall in-hospital mortality was 60.5%, with no differences between AMI with or without ST-segment elevation, and was 62.6% at 30 days. Conclusion: Morbidity and mortality of CS are high despite the high rate of reperfusion therapy used.

Prognostic Value of Insulin Resistance Assessed by HOMA-IR in Non-Diabetic Patients with Decompensated Heart Failure.

The predictive value of insulin resistance in patients hospitalized with heart failure is unknown. To evaluate prognostic value of insulin resistance (defined by a HOMA IR ≥ 2.5) for the combined event of death and readmission at 90 and 365 days post discharge and to determine if there are differences according to ejection fraction. Prospective study of 156 p hospitalized for acute heart failure without diabetes. A total of 83 years, 48% female, EF ≤ 45% 48%. Of 28% presented HOMA ≥2.5. HOMA IR ≥2.5 was associated with combined event (OR 2.4; 95% CI 1.9-5.1; P: 0.02) at 90 days. A multivariate analysis demonstrated its independent predictive value (OR 2.5, 95% CI 1.1-5.8; P: 0.03). At 1 year follow-up HOMA IR did not predict events. The predictive value of HOMA-IR was not associated with ventricular function. HOMA IR index was a predictor of a combined event at 90 days in our population. It is a simple determination that could contribute to identify higher risk patients during this vulnerable post-discharge phase. These data must be validated in larger studies.

Clinical characteristics and evolution of patients with cardiogenic shock in Argentina in the context of an acute myocardial infarction with ST segment elevation. Data from the nationwide ARGEN-IAM-ST Registry.

Cardiogenic Shock is one of the main causes of death in ST segment Elevation Myocardial Infarction. To know the clinical characteristics, in-hospital evolution and mortality of patients with Cardiogenic Shock. Patients enrolled in the ARGEN-IAM-ST Registry were analyzed. Predictors of Cardiogenic Shock and death during hospital stay were established. A total of 6122 patients were admitted between 2015 and 2022. Cardiogenic Shock was present in 10.75% of cases. Patients with CS were older (64.5 vs 60 years), more females (41% vs 36%), with more antecedents of infarction and a higher prevalence of anterior location of infarction and multivessel disease. They were also less revascularized (88.5% vs 91.5%) and had a higher incidence of failed angioplasty (15.7% vs 2.7%). They also evidenced a higher occurrence of mechanical complications (6.8% vs 0.4%), ischemic recurrence (7.4% vs 3.4%) and cardiac arrest on admission (44.8% vs 2.6%). All the differences described showed statistical significance with P < 0.05. Overall mortality was 58% in contrast to 2.77% in patients without Cardiogenic Shock (P < 0.001). Only age, DBT, and early cardiac arrest were independent predictors of shock on admission whereas age, female gender, cardiac arrest on admission and failed angioplasty were independent predictors of death. One out of 10 patients with ST Elevation Myocardial Infarction presented cardiogenic shock. Its clinical characteristics were similar to those described more than 20 years ago. Despite a high use of reperfusion strategy cardiogenic shock continues to have a very high mortality Argentina.

Shock Index, Modified Shock Index, and Age-adjusted Shock Index as Predictors of In-hospital Death in Acute Heart Failure. Sub Analysis of the ARGEN IC.

Decompensated heart failure (DHF) is an important cause of in-hospital death in the coronary care unit. Estimating this risk becomes a clinical challenge. The shock index (IShock) and its variances have proven to be useful in predicting mortality in other pathologies and are easily obtained at admission. Evaluate the predictive capacity of IShock and its variants for in-hospital mortality in patients with DHF. Retrospective study of patients (p) prospectively and consecutively included in the ARGEN IC national registry. IShock, was calculated using the formula: HR/TAS, IShockM was calculated using HR/TAM, and IShock adjusted for age was calculated using the formula IShock x age. These indices were analyzed using the ROC curve and the Youden index to find the value that predicted in-hospital mortality with the greatest sensitivity and specificity. The prognostic value of the indices for in-hospital mortality was analyzed. Univariate and multivariate analyses were performed. Patients with cardiogenic shock were excluded from the analysis. Eight hundred seventy-nine patients. Age 74 years (IQR 25-75 64-83). 60% male. 74% hypertensive, 33% diabetic and 42% had ejection fraction <40%. In-hospital mortality was 6.6%. According to Youden 's test, the best value for predicting IShock mortality was 0.9, for IShockM of 1.26 with and for the adjusted IShock of 50.4. The last two showed an independent predictive value in different multivariate models. The IShockM and the IShock x age, taken at the patient´s admission for decompensated heart failure, are very easily obtained at no additional cost providing useful information on hospital major outcomes.

Valor pronóstico del índice de shock en el infarto de miocardio. Datos del Registro Argentino de infarto con elevación del segmento ST (ARGEN IAM-ST) / Prognostic value of the shock index in myocardial infarction. Data from Argentine Registry of ST-segment elevation infarct (ARGEN IAM-ST)

Resumen El índice de shock (IS) se obtiene mediante un cálculo simple del cociente entre la frecuencia cardíaca (FC) y la tensión arterial sistólica (PAS) (IS: FC/TAS) y el índice de shock ajustado por edad (ISA) multiplicando el IS x edad. Evaluamos su valor predictivo para el evento combinado intrahospitalario (EC) muerte y/o shock cardiogénico (SC) y de los eventos individuales en los pacientes incluidos en el registro argentino de infarto con elevación del segmento ST (ARGEN-IAM-ST). Se excluyeron 248 con SC de ingreso. Se realizaron curvas ROC para ambos índices utilizando el mejor punto de corte para dicotomizar la población. Se incluyeron 2928 pacientes. Edad (mediana) 60 años (RIC 25-75% 53-68), varones 80%, EC: 6.4%. Un 30.5% tuvo IS ≥ 0.67 y éstos presentaron mayor incidencia de EC: 11% vs. 4% (p < 0.001), shock cardiogénico (8% vs. 2.6%, p <0.0001) y muerte (7.3% vs. 3%, p < 0.0001) que los pacientes con IS < 0.67. Un 28% tuvo ISA ≥ 41.5. Estos presentaron más EC: 14% vs. 3%, p < 0.001, SC: 10% vs. 2%, (p < 0.001) y muerte: 9.5% vs. 2.3%, (p < 0.001) comparados con los pacientes con valores ISA < 41.5. El área bajo la curva ROC del ISA para EC fue significativamente mejor que la del IS (0.72 vs. 0.62, p < 0.001).En los modelos de análisis multivariados reali zados, el IS tuvo un OR de 2.56 (IC95% 1.56-4.02; p < 0.001) y el ISA de 3.43 (IC95% 2.08-5.65; p<0.001) para EC. El IS y el ISA predicen muerte y/o el desarrollo de shock cardiogénico intrahospitalario en una población no seleccionada de infartos con elevación del ST.

Abstract The shock index (IS) is the quotient between the heart rate (HR) and the systolic blood pressure (SBP) (IS: HR / SBT), and the age-adjusted shock index (ISA) multiplying the IS by age. We evaluated its predictive value for the combined in-hospital event (EC), death and / or cardiogenic shock (CS) and for individual events in the patients included in the Argentine registry of ST-segment elevation infarction (ARGEN-ST-AMI); 248 with CS on admission were excluded. ROC curves were made for both indices using the best cut-off point to dichotomize the population. The analysis included 2928 subjects. Age (median) 60 years (IQR 25-75% 53-68), men 80%, EC: 6.4%; 30.5% had IS ≥ 0.67, and they had a higher incidence of EC: 11% vs. 4% (p < 0.001), cardiogenic shock (8% vs. 2.6%, p <0.0001) and death (7.3% vs. 3%), p <0.0001) than patients with IS < 0.67. A 28% had ISA ≥ 41.5. These presented plus EC: 14% vs. 3%, p < 0.001, SC: 10% vs. 2%, (p < 0.001) and death: 9.5% vs. 2.3%, (p < 0.001) compared with patients with values < 41.5. The area under the ROC curve of the ISA for EC was significantly better than that of the IS (0.72 vs. 0.62, p < 0.001). In the multivariate analysis models performed, the IS had an OR: 2.56 (95% CI 1.56-4.02; p < 0.001) and the ISA: 3.43 (95% CI 2.08-5.65; p < 0.001) for EC. The IS and ISA predict death and / or the development of in-hospital cardiogenic shock in an unselected population of ST elevation infarcts.

[Prognostic value of the shock index in myocardial infarction. Data from Argentine Registry of ST-segment elevation infarct (ARGEN IAM-ST)]. / Valor pronóstico del índice de shock en el infarto de miocardio. Datos del Registro Argentino de infarto con elevación del segmento ST (ARGEN IAM-ST).

The shock index (IS) is the quotient between the heart rate (HR) and the systolic blood pressure (SBP) (IS: HR / SBT), and the age-adjusted shock index (ISA) multiplying the IS by age. We evaluated its predictive value for the combined in-hospital event (EC), death and / or cardiogenic shock (CS) and for individual events in the patients included in the Argentine registry of ST-segment elevation infarction (ARGEN-ST-AMI); 248 with CS on admission were excluded. ROC curves were made for both indices using the best cut-off point to dichotomize the population. The analysis included 2928 subjects. Age (median) 60 years (IQR 25-75% 53-68), men 80%, EC: 6.4%; 30.5% had IS = 0.67, and they had a higher incidence of EC: 11% vs. 4% (p < 0.001), cardiogenic shock (8% vs. 2.6%, p <0.0001) and death (7.3% vs. 3%), p <0.0001) than patients with IS < 0.67. A 28% had ISA = 41.5. These presented plus EC: 14% vs. 3%, p < 0.001, SC: 10% vs. 2%, (p < 0.001) and death: 9.5% vs. 2.3%, (p < 0.001) compared with patients with values < 41.5. The area under the ROC curve of the ISA for EC was significantly better than that of the IS (0.72 vs. 0.62, p < 0.001). In the multivariate analysis models performed, the IS had an OR: 2.56 (95% CI 1.56-4.02; p < 0.001) and the ISA: 3.43 (95% CI 2.08-5.65; p < 0.001) for EC. The IS and ISA predict death and / or the development of in-hospital cardiogenic shock in an unselected population of ST elevation infarcts.

El índice de shock (IS) se obtiene mediante un cálculo simple del cociente entre la frecuencia cardíaca (FC) y la tensión arterial sistólica (PAS) (IS: FC/TAS) y el índice de shock ajustado por edad (ISA) multiplicando el IS x edad. Evaluamos su valor predictivo para el evento combinado intrahospitalario (EC) muerte y/o shock cardiogénico (SC) y de los eventos individuales en los pacientes incluidos en el registro argentino de infarto con elevación del segmento ST (ARGEN-IAM-ST). Se excluyeron 248 con SC de ingreso. Se realizaron curvas ROC para ambos índices utilizando el mejor punto de corte para dicotomizar la población. Se incluyeron 2928 pacientes. Edad (mediana) 60 años (RIC 25-75% 53-68), varones 80%, EC: 6.4%. Un 30.5% tuvo IS = 0.67 y éstos presentaron mayor incidencia de EC: 11% vs. 4% (p < 0.001), shock cardiogénico (8% vs. 2.6%, p <0.0001) y muerte (7.3% vs. 3%, p < 0.0001) que los pacientes con IS < 0.67. Un 28% tuvo ISA = 41.5. Estos presentaron más EC: 14% vs. 3%, p < 0.001, SC: 10% vs. 2%, (p < 0.001) y muerte: 9.5% vs. 2.3%, (p < 0.001) comparados con los pacientes con valores ISA < 41.5. El área bajo la curva ROC del ISA para EC fue significativamente mejor que la del IS (0.72 vs. 0.62, p < 0.001).En los modelos de análisis multivariados realizados, el IS tuvo un OR de 2.56 (IC95% 1.56-4.02; p < 0.001) y el ISA de 3.43 (IC95% 2.08-5.65; p <0.001) para EC. El IS y el ISA predicen muerte y/o el desarrollo de shock cardiogénico intrahospitalario en una población no seleccionada de infartos con elevación del ST.

El índice de shock e índice de shock ajustado por edad como predictores de muerte en la insuficiencia cardíaca descompensada / Shock Index and Age-Adjusted Shock Index as Predictors of Mortality in Decompensated Heart Failure

RESUMEN Introducción: El índice de shock (IShock), calculado a partir de los valores al ingreso de la frecuencia cardíaca (FC) y tensión arterial sistólica (TAS) y el IShock ajustado por edad, son herramientas que han demostrado utilidad pronóstica en algunos contextos clínicos; sin embargo, su valor pronóstico en la insuficiencia cardíaca descompensada (ICD) es desconocido. Objetivo: evaluar la capacidad pronóstica para mortalidad total intrahospitalaria de ambos índices en pacientes ingresados a unidad coronaria por ICD. Material y métodos: Estudio retrospectivo de pacientes consecutivos ingresados en 2 unidades coronarias durante el periodo enero 2010/agosto 2020. Se calcularon ambos índices, se determinó su valor predictivo y mediante curva ROC se definieron los valores de corte con mejor combinación de sensibilidad y especificidad. Se efectuó análisis multivariado para encontrar los predictores independientes de mortalidad intrahospitalaria. Resultados: Población: 1472 pacientes. Edad (mediana) 81 años, 50% con fracción de eyección ventricular izquierda <40%, y 50% con antecedentes de ICD previa. Mortalidad intrahospitalaria 6,2%. Un IShock ≥0,58 e IShock ajustado por edad ≥45,6 (hallados por índice de Youden) fueron predictores de mortalidad. En el análisis multivariado que incluyó edad, tensión arterial sistólica (TAS) <115 mmHg, nitrógeno ureico en sangre (BUN) >43 mg/dL, creatinina >2,75 mg/dL, hemoglobina <10 g/dL y el ISHock ≥0,58, solo mantuvieron su valor predictivo la edad, el BUN >43 mg/dL y la anemia. En un modelo multivariado donde se evaluó al IShock ajustado por edad ≥45,6 junto a las otras variables (excepto edad), éste fue predictor independiente (OR 2,41 IC95% 1,37-4,2 p <0,01) al igual que el BUN >43 mg/dL y la anemia. Conclusión: Un cálculo sencillo como el IShock ajustado por edad es de gran utilidad en la predicción de la mortalidad hospitalaria de los pacientes internados con ICD y agrega información adicional a las variables pronósticas clásicas.

ABSTRACT Background: Shock index (SI), calculated as the ratio of heart rate (HR) to systolic blood pressure (SBP) obtained on admission, and age-adjusted SI are tools that have already demonstrated prognostic value in some clinical contexts, but their prognostic value in decompensated heart failure (DHF) is unknown. Objective: The aim of this study was to evaluate the prognostic ability of both indices for total in-hospital mortality in patients admitted to the coronary unit for DHF. Methods: We conducted a retrospective study of consecutive patients admitted to 2 coronary care units between January 2010 and August 2020. Both indices and their respective predictive values were calculated. The cutoff point values with the best combination of sensitivity and specificity were defined using the ROC curve. Multivariate analysis was performed to identify independent predictors of in-hospital mortality. Results: Population: 1472 patients. Median age was 81 years, 50 had left ventricular ejection fraction <40% and 50% had a history of DHF. In-hospital mortality 6.2%. Youden's index identified SI ≥0.58 and age-adjusted SI ≥45.6 as predictors of mortality. On multivariate analysis including age, systolic blood pressure (SBP) <115 mmHg, blood urea nytrogen (BUN) >43 mg/ dL, creatinine level >2.75 mg/dL, hemoglobin (Hb) <10 g/dL and SI ≥0.58, only age, BUN >43 mg/dL and anemia remained as independent predictors of in-hospital mortality. On multivariate analysis, when age-adjusted SI ≥45.6 was analyzed with the other variables (but not with age), the independent predictors were age-adjusted SI ≥45.6 (OR 2.41; 95% CI, 1.37-4.2; p <0.01), BUN >43 mg/dL and anemia. Conclusion: A simple calculation as age-adjusted SI is highly useful to predict in-hospital mortality in patients hospitalized with DHF and provides additional information to the classic prognostic variables.

Mortalidad por infarto agudo de miocardio en el registro continuo ARGEN-IAM-ST. Su relación con las diferentes terapias de reperfusión / Mortality of Acute Myocardial Infarction in the Continuous Registry ARGEN-AMI-ST and its Relationship with the Different Reperfusion Therapies

RESUMEN Introducción: El tratamiento de reperfusión es la terapéutica de mayor eficacia para reducir la mortalidad del infarto agudo de miocardio con elevación del segmento ST (IAMCEST) , y su efectividad es inversamente proporcional al tiempo total de isquemia. El mayor desafío es instrumentar su aplicación en la vida real y corregir en forma continua los desvíos o las barreras que se presentan en la práctica cotidiana. Objetivos: Evaluar la mortalidad con las diferentes modalidades de reperfusión, su relación con el tiempo de tratamiento y su efectividad en un registro prospectivo multicéntrico del mundo real de Argentina. Material y Métodos: estudio prospectivo, multicéntrico de carácter nacional, incluidos los pacientes con IAMCEST hasta las 36 h del comienzo de los síntomas (ARGEN-IAM-ST registro continuo). Resultados: participaron 2464 pacientes de 78 centros entre 2015 y 2019. El 88,5% recibió tratamiento de reperfusión. La mortalidad fue de 8,68%. Los pacientes tratados con reperfusión tuvieron una mortalidad de 7,81% versus 15,38% sin tratamiento (p <0,001). La mortalidad con angioplastia primaria fue 7,51%, con trombolíticos 9,03%, con estrategia farmacoinvasiva 2,99% y con angioplastia de rescate 9,40%, sin diferencia estadísticamente significativa entre angioplastia primaria y trombolíticos (OR 0,81 IC 95% 0,56-1,18, p = ns). Los pacientes fallecidos fueron de mayor edad, con mayor proporción de mujeres e insuficiencia cardíaca. El tratamiento de reperfusión e ingreso a la institución dentro de 3 horas del comienzo de los síntomas se asoció a menor mortalidad. Los pacientes fallecidos con angioplastia primaria tuvieron mayor tiempo total de isquemia (378 minutos versus 285 minutos, p < 0,001). Conclusiones: La mortalidad por IAMCEST se relacionó con el acceso a la reperfusión y su precocidad. Fue mucho mayor en los pacientes no reperfundidos, y menor cuando la reperfusión se efectuó en forma precoz dentro de las primeras tres horas del comienzo de los síntomas. En los pacientes tratados con angioplastia primaria la mortalidad se incrementó con mayor tiempo total de isquemia. Este registro de la práctica real del tratamiento del IAMCEST refuerza la necesidad de una mejor articulación del sistema de atención para bajar los tiempos y utilizar la estrategia mejor y más oportuna.

ABSTRACT Background: reperfusion treatment is the most effective therapy in reducing mortality from acute ST elevation myocardial infarction and its effectiveness is inversely proportional to the total time of ischemia. The greatest challenge is to implement its application in real life and continuously correct the deviations or barriers that arise in daily practice. Objectives: to evaluate mortality with the different reperfusion modalities, its relationship with treatment time and to evaluate its effectiveness. Methods: a prospective, multicenter national study, including patients with STEMI up to 36 h after symptoms began (ARGENAMI-ST continuous registry). Results: 2464 patients were included from 2015 to 2019 in 78 centers. 88.5% received reperfusion treatment. Mortality was 8.68%. The patients treated with reperfusion had a mortality of 7.81% versus 15.38% without treatment (p <0.001). Mortality with primary angioplasty was 7.51%, thrombolytics 9.03%, pharmacoinvasive strategy 2.99%, and rescue angioplasty 9.40%, with no statistically significant difference between primary angioplasty and thrombolytics (OR 0.81; 95% CI 0.56-1.18, p = ns). The deceased patients were older, a higher proportion of women, and heart failure. Reperfusion treatment and admission to the institution within 3 hours of starting symptoms were associated with lower mortality. Patients who died with primary angioplasty had a longer total ischemia time (378 minutes versus 285 minutes, p <0.001). Conclusions: mortality from STEMI was related to access to reperfusion and its earliness. It was much higher in non-reperfused patients, and lower when reperfusion was carried out early within the first three hours of the onset of symptoms. In patients treated with primary angioplasty, mortality increased with a longer total ischemia time. This record of the actual practice of the treatment of infarction reinforces the need for a better articulation of the care system to reduce times and use the best timely strategy.

Diabetes as a Predictor of In-Hospital and One-Year Outcomes After Decompensated Heart Failure.

Diabetes and heart failure are closely interdependent, but its significance in decompensated heart failure (DHF) is not uniformly accepted. OBJECTIVE: To compare mortality between diabetics and nondiabetics with DHF. METHODS AND RESULTS: In-hospital and 1-year mortality of 1004 consecutive patients with DHF: 25.6% diabetics; median age was 81, 53% male. Diabetics were younger, more often male, with higher prevalence of ischemic etiology and reduced ejection fraction. Congestion was the most prevalent finding in both groups. In hospital mortality was 6.3% vs 6.6 % in nondiabetics and diabetics respectively and 1-year mortality was 35.77% in nondiabetics and 29.3% in diabetics. There were no significant differences in mortality at univariate and multivariate analyses. We applied a propensity score restricted to 378 patients, 189 (50%) diabetics and 189 (50%) and no significant differences were found. CONCLUSION: Diabetes had no impact on prognosis in DHF. Advanced age may played a major role in outcomes i thus making less relevant the presence of diabetes.

SCA con elevación del ST: impacto del tiempo al diagnóstico en el tiempo puerta-balón en el mundo real. Datos del registro ARGEN-IAM-ST / ST-Segment Elevation ACS: Impact of Time to Diagnosis on Door-To-Balloon Time in the Real World. Data from the ARGEN-IAM-ST Registry

RESUMEN • Introducción: El tiempo trascurrido desde el inicio de los síntomas de infarto hasta el diagnóstico (TAD) puede influir en lograr un tiempo puerta-balón (TPB) <90 min. Material y métodos: Análisis retrospectivo que incluyó 1518 pacientes ingresados en forma prospectiva y consecutiva al registro ARGEN-IAM-ST. El 37,8% de ellos fue tratado con un TPB <90 min y el TAD (mediana) fue de 120 min (RIC 60-266). Se dividió a la población de acuerdo al TAD en dos grupos: menor de 120 min y mayor o igual que 120 min. Un TPB <90 min se logró más frecuentemente en el primer grupo (TAD <120 min): 44%, vs. 32,2% en el segundo grupo (p <0,001). Resutados: En el 56% de los pacientes con ATC in situ y TAD <120 min se logró un TPB <90 min, vs. en el 37,1% de quienes tuvieron un TAD >120 min (p <0,001). En pacientes derivados, no hubo diferencias en TPB <90 min de acuerdo al TAD: 27,5% vs. 25,7 (p: 0,3). En pacientes ingresados en horario laborable, el TPB <90 min se logró con TAD <120 min en un 49,8% vs. 36,3% con TAD >120 min (p: 0,003); la frecuencia siguió un patrón similar en los pacientes ingresados en horarios no laborables: 41,9% vs. 30,4%, respectivamente (p <0,001). Los predictores independientes de lograr un TPB <90 min en el análisis multivariado fueron la edad <75 años: OR 1,57 (1,1-2,25; p: 0,01), ATC en horario laborable: OR 1,32 (1,04-1,67; p: 0,002), ATC in situ: OR 2,4 (1,9-3,0; p <0,001), tener un ECG prehospitalario: OR 2,22 (1,73-2,86; p <0,001) y un TAD <120 min: OR 1,53 (1,23-1,9; p <0,001). Conclusiones: En los pacientes con un TAD <120 minutos se logra más frecuentemente un TPB <90 min, especialmente en los tratados in situ y en horario laborable. En los pacientes derivados, solo 1 de cada 3 logra un TPB <90 min y no hay relación con el TAD.

ABSTRACT • Background: Time elapsed from the onset of symptoms to diagnosis (TTD) can influence in achieving a door-to-balloon time <90 min (DBT <90 min). Methods: A retrospective analysis was performed on 1,518 patients prospectively and consecutively included in the ARGEN-AMI-ST registry. In 37.8% of cases. patients were treated with DBT <90 min and a median TTD of 120 min (IQR 60-266). The population was divided according to TTD above or below 120 min. A DBT <90 min was achieved more frequently in those with TTD <120 min: 44% vs. 32.2% (p <0.001) respectively. Results: In patients with in situ percutaneous coronary intervention (PCI) and TTD <120 min, DBT <90 min was achieved in 56% vs. 37.1% of cases with TTD >120 min (p <0.001). In referred patients, there were no differences in DBT <90 min according to TTD: 27.5% vs. 25.7% (p: 0.3). In patients admitted during working hours, DBT <90 min was achieved with TTD <120 min in 49.8% vs. 36.3% with TTD >120 min (p: 0.003), as well as in patients admitted during non-working hours: 41.9% vs. 30.4% (p <0.001). The independent predictors of achieving a DBT <90 min in the multivariate analysis were age <75 years: OR 1.57 (1.1-2.25; p: 0.01), PCI during working hours: OR 1.32 (1.04-1.67; p: 0.002), PCI in situ: OR 2.4 (1.9-3.0; p <0.001), having a pre-hospital ECG: OR 2.22 (1.73-2.86; p <0.001) and a TTD <120 min: OR 1.53 (1.23-1.9; p <0.001). Conclusions: In patients with TTD <120 minutes, a DBT <90 minutes is more frequently achieved, especially in those treated in situ and during working hours. In referred patients, only 1 in 3 achieves a DBT<90 min and there is no relationship with TTD.

Child and adolescent psychiatry training curriculum: a global trainee's perspective.

This article is a summary of perspectives on training curricula from child and adolescent psychiatry trainees globally. We aimed to identify the relative strengths, weaknesses and gaps in learning needs from a trainee's perspective. The 20 early-career child psychiatrists who contributed are from 16 countries and represent all the five continents. We could identify some global challenges as well as local/regional challenges that need to be addressed to develop competent child psychiatrists.

Predictores de la elección de nuevos anticoagulantes directos en la fibrilación auricular y su adherencia al año / Predictors for the Use of New Direct Anticoagulants in Atrial Fibrillation and Their One-Year Adherence

RESUMEN Introducción: Los hombres con CHA2DS2-Vasc ≥ 1 o las mujeres con CHA2DS2-Vasc ≥ 2 y fibrilación/aleteo auricular tienen indicación de tratamiento antitrombótico al alta. Objetivos: Analizar la prevalencia del uso de anticoagulantes en esta población; hallar predictores del uso de nuevos anticoagulantes orales; y analizar la persistencia al año del tratamiento con nuevos anticoagulantes orales. Resultados: Pacientes consecutivos: 484. Los criterios de exclusión fueron la muerte intrahospitalaria (n: 12) y CHA2DS2-Vasc de 0 en ambos géneros y de 1 en mujeres (67 pacientes). Los pacientes analizados fueron 405. Edad mediana: 76 años, género femenino: 46%, HTA: 76%, diabetes: 25%, accidente cerebrovascular previo: 10%, antecedentes de fibrilación/aleteo auricular: 30%. Estrategia de control de ritmo: 66%. Fueron anticoagulados al alta 293 pacientes (72%). Entre los pacientes anticoagulados, los nuevos anticoagulantes orales fueron los más utilizados: 63,5%, especialmente en los menos añosos (74 versus 79,5 años, p: 0,001), con menos antecedentes de accidente cerebrovascular (5,8% versus 18%, p < 0,001), menor CHA2DS2-Vasc mediana (3 versus 4, p < 0,01) y HAS-BLED mediana (1 versus 2, p < 0,01) y en más pacientes con ritmo sinusal al momento del alta (73,8% versus 54,7%, p < 0,001). De los 165 pacientes externados con nuevos anticoagulantes orales y seguidos al año, el 55,7% mantuvieron el nuevo anticoagulante oral indicado, un 29,69% habían discontinuado la anticoagulación y el 14,5% rotó a acenocumarol. Conclusiones: En nuestro trabajo, se anticoagula al alta solo al 70% de los pacientes. Se utilizaron nuevos anticoagulantes orales en más de la mitad de los casos, especialmente en los pacientes de menor riesgo clínico. Al año de seguimiento, cada 10 pacientes medicados al alta con nuevos anticoagulantes orales, 6 persisten con ese tratamiento, 1 rota a acenocumarol y 3 dejan de estar anticoagulados.

ABSTRACT Background: Men with CHA2DS2-Vasc score ≥1 or women with CHA2DS2-Vasc score ≥2 and atrial fibrillation/flutter have high indication of antithrombotic treatment. Objective: The aim of this study was to analyze the prevalence of anticoagulant therapy in this population, to find predictors for the use of new oral anticoagulants and to analyze the one-year adherence to treatment. Methods: A total of 484 consecutive patients were included in the study. Exclusion criteria were in-hospital mortality (n=12) and CHA2DS2-Vasc score of 0 in both genders and 1 in women (n=67). Finally, 405 patients were analyzed with median age of 76 years, 46% women, 76% hypertensive, 25% diabetic, 10% with previous stroke and 30% with history of atrial fibrillation/flutter. Results: A rhythm control strategy was used in 66% of cases and 293 patients were anticoagulated at discharge (72%). Among anticoagulated patients, 63.5% received new oral anticoagulants, especially those who were younger (74 vs. 79.5 years, p=0.001), with lower history of stroke (5.8% vs.18%, p<0.001), lower median CHA2DS2-Vasc (3 vs.4, p<0.01) and HAS-BLED (1 vs. 2, p<0.01) scores and with sinus rhythm at discharge (73.8% vs. 54.7%, p<0.001). Among 165 patients discharged with new oral anticoagulants and followed up for one year, 55.7% adhered to the indicated new oral anticoagulant, 29.69% had discontinued the anticoagulation treatment and 14.5% had switched to acenocoumarol. Conclusions: The study shows that only 70 of patients are anticoagulated at discharge. New oral anticoagulants were used in more than half of cases, especially in patients at lower clinical risk. At one-year follow-up, 6 out of every 10 patients with indication of new oral anticoagulants at discharge continue this treatment, 1 switches to acenocoumarol and 3 abandon anticoagulant therapy.

Paro cardíaco durante las primeras 24 horas del ingreso hospitalario en los síndromes coronarios agudos con elevación del ST. Registro ARGEN-IAM-ST / Cardiac Arrest within the First 24 Hours after Hospital Admission in ST-segment Elevation Acute Coronary Syndromes. The ARGEN-IAM-ST Registry

RESUMEN Introducción: El paro cardiorrespiratorio (PCR) en el contexto de un síndrome coronario agudo es una causa importante de muerte, tanto extra como intrahospitalaria. Objetivo: El objetivo de nuestro trabajo fue describir la prevalencia, las características y la evolución intrahospitalaria de los pacientes que presentaron PCR durante las primeras 24 horas del ingreso (PCR 24 h) en la población del registro ARGEN-IAM-ST. Resultados: la prevalencia de PCR 24 horas fue del 7,8% (136/1754 pacientes). Los que presentaron PCR 24 h eran más añosos (mediana: 63 vs 61 años, p < 0,001), tuvieron más prevalencia de shock cardiogénico (42,6% vs 3%, p < 0,01) y mortalidad intrahospitalaria (66% vs 4%, p < 0,001). La mortalidad global del registro fue de 8,8% (154 muertes/1754 pacientes). Del total de las muertes intrahospitalarias (n:154), el 58% ocurrió en los pacientes que presentaron PCR 24 h . Conclusiones: El PCR 24 h en pacientes con un síndrome coronario agudo con elevación del ST es un evento grave y representa el 60% de las muertes intrahospitalarias.

ABSTRACT Background: Cardiac arrest (CA) in the setting of an acute coronary syndrome is an important cause of in-hospital and out-of hospital mortality. Objectives: The aim of this study was to describe the prevalence, clinical characteristics, and in-hospital outcome of patients from the ARGEN-IAM-ST registry with CA within the first 24 hours after hospital admission. Results: The prevalence of CA within the first 24 hours was 7.8% (136/1,754 patients). These patients were older (median age 63 vs. 61 years, p<0.001) and had higher prevalence of cardiogenic shock (42.6% vs., 3%, p<0.01) and of in-hospital mortality (66% vs. 4%, p<0.001). Overall mortality of the registry was 8.8% (154/1754) and 58% occurred in patients with CA within the first 24 hours after admission. Conclusions: Cardiac arrest within 24 hours in patients with ST- segment elevation acute coronary syndrome is a serious event representing 60% of in-hospital mortality.

Cálculo dinámico del filtrado glomerular en los pacientes con insuficiencia cardíaca descompensada / Estimation of Kinetic Glomerular Filtration Rate in Patients with Decompensated Heart Failure

RESUMEN Introducción: La coexistencia de insuficiencia cardíaca descompensada (ICD) e insuficiencia renal aguda (IRA) conlleva internaciones más prolongadas y, en algunos casos, mayor mortalidad. Objetivos: Evaluar si la tasa de filtrado glomerular dinámico (TFGD) calculada mediante la fórmula de Chen permite predecir el desarrollo de IRA o muerte durante la internación en pacientes con ICD. Material y métodos: Estudio retrospectivo de pacientes consecutivos. Se calculó la TFGD utilizando los valores de creatinina del ingreso y a las 24 h. Se realizó una curva ROC para hallar el punto que con mejor sensibilidad y especificidad predijera eventos. Se evaluó un punto final de evento combinado (EC) definido como el desarrollo de IRA o muerte. Se definió la IRA de acuerdo a la guía KDIGO. El seguimiento fue hospitalario. El criterio de exclusión principal fue la existencia de antecedentes de insuficiencia renal crónica. Resultados: De un total de 813 pacientes, 190 fueron excluidos por tener insuficiencia renal crónica. Se analizaron 608 pacientes. Edad (mediana): 81 años (RIC 25-75%: 73-87), hombres: 48%, diabéticos: 25,5%, hipertensos: 76%, infarto previo: 19,4%, disfunción sistólica (Fey < 45%): 46,8%, creatinina de ingreso (mediana): 1,05 mg/dl. La incidencia de EC fue de 41,1%. La edad, el sexo y la presencia de comorbilidades no incidieron en la tasa de presentación de EC, pero la TFGD de este grupo de pacientes fue significativamente menor (mediana: 50,7 ml/min, vs. 57,9 ml/min, p < 0,01) y esta variable fue un predictor independiente de mortalidad. El mejor valor por curva ROC para EC de la TFGD fue 60 ml/min (ABC 0,60) y estuvo presente en el 58,9% de los pacientes. Fueron predictores de ello la edad, el sexo femenino y la presencia de HTA y de diabetes. Conclusiones: La TFGD resulta ser un predictor independiente de EC intrahospitalarios en la ICD; sin embargo, presenta escasa relevancia clínica por su baja especificidad.

ABSTRACT Background: The coexistence of decompensated heart failure (DHF) and acute renal failure (ARF) is associated with longer hospital stay and greater mortality. Objectives: The aim of this study was to evaluate whether kinetic glomerular filtration rate (KeGFR) estimated with Chen´s equation can predict the development of ARF or mortality during hospitalization in patients with DHF. Methods: We conducted a retrospective study of consecutive patients with estimated kinetic glomerular filtration rate using serum creatinine levels on admission and at 24 hours. The primary endpoint was a composite of ARF or mortality, and a ROC curve was built to find the cutoff value with the best sensitivity and specificity to predict events. Acute renal failure was defined according to the KDIGO guideline. Patients were followed-up throughout hospitalization and those with a history of chronic renal failure were excluded from the study. Results: Among 813 patients, 190 were excluded due to chronic renal failure and 608 patients were analyzed. Median age was 81 years (IQR 25-75%: 73-87) and 48% were men; 25.5% were diabetics, 76% had hypertension, 19.4% had history of prior myocardial infarction and 46.8% presented left ventricular systolic dysfunction defined as left ventricular ejection fraction <45%. Median creatinine level on admission was 1.05 mg/dl. The incidence of the composite event was 41.1%. Age, sex and comorbidities were similar in patients with and without the composite event, but KeGFR was significantly lower in this group of patients (median: 50.7 ml/min vs. 57.9 ml/min, p<0.01) and resulted an independent predictor of mortality. The analysis of the ROC curve revealed that a cutoff point of 60 ml/kg/min for KeGFR (AUC 0.60) had the best diagnostic accuracy to predict the composite event and was present in 58.9% of the patients. Age, female sex, hypertension and diabetes were predictors of the composite event. Conclusions: Kinetic glomerular filtrate rate can be used as an independent predictor of the composite event, but has no clinical relevance due to its low specificity.

Síndromes coronarios agudos sin elevación del segmento ST y troponina ultrasensible. ¿Es el final de la estrategia conservadora? / Non-ST Segment Elevation Acute Coronary Syndromes and High-Sensitivity Cardiac Troponin T: Is this the end of the Conservative Strategy?

RESUMEN Introducción: Los síndromes coronarios agudos sin elevación del segmento ST con troponina ultrasensible elevada son considerados de alto riesgo por lo que se recomienda una estrategia invasiva . Objetivos: Evaluar los eventos hospitalarios de los pacientes tratados con una estrategia conservadora; analizar la prevalencia de troponina ultrasensible positiva y su correlación con eventos hospitalarios; y establecer el valor predictivo de la troponina ultrasensible para eventos hospitalarios y compararla con un modelo de riesgo clínico. Materiales y métodos: Estudio observacional y retrospectivo. Fueron incluidos pacientes ingresados a una unidad coronaria de 2 centros con síndrome coronario agudo sin elevación del segmento ST, tratados con una estrategia conservadora en el período 2012/2017. El modelo de riesgo clínico utilizado se basó en el Score TIMI con las siguientes variables: edad superior a 65 años, 2 o más dolores en la últimas 24 h, cambios electrocardiográficos, factores de riesgo coronario, antecedentes coronarios y aspirina previa, excluida la troponina ultrasensible. Se comparó mediante curva ROC la precisión pronóstica de la troponina ultrasensible y el puntaje del modelo de riesgo clínico para eventos hospitalarios. Eventos hospitalarios combinados: Angina recurrente, infarto de miocardio y muerte. El punto de corte utilizado para considerar la troponina ultrasensible elevada fue igual o mayor de 14 pg/ml. Resultados: Fueron incluidos 245 pacientes. La edad mediana era 65 años (57-76), y el 74% eran hombres. El puntaje del modelo de riesgo clínico fue 3 (1-4) y la troponina ultrasensible positiva se ubicó en el 65%. Eventos hospitalarios: 55/245 pacientes (22,4%): Angina recurrente, 20,4%: infarto tipo, Q 1,6%; muerte, 0,4%. La precisión pronóstica para eventos hospitalarios de la troponina ultrasensible fue 0,56 (0,48-0,65), para el modelo de riesgo clínico 0,58 (0,49-0,67); (p = 0,92) y el Score TIMI 0,56 (p: 0,16). Conclusiones: En pacientes con síndrome coronario agudo sin elevación del segmento ST ni la troponina ultrasensible ni las variables clínicas al ingreso fueron consistentes para predecir los eventos hospitalarios. Utilizar solo los niveles de troponina ultrasensible para guiar la estrategia terapéutica puede determinar una indicación innecesaria de procedimientos con el consecuente riesgo inherente.

ABSTRACT Background: An invasive strategy is recommended in high-risk non-ST segment elevation acute coronary syndromes with elevated high-sensitivity cardiac troponin T levels. Objectives: The aim of this study was to evaluate in-hospital events in patients undergoing a conservative strategy, analyze the prevalence of elevated high-sensitivity cardiac troponin T levels and its correlation with in-hospital events and establish the predictive value of the biomarker for in-hospital events comparing it with a clinical risk model. Methods: We conducted an observational and retrospective study. Patients admitted to a coronary care unit with non-ST segment elevation acute coronary syndrome in two centers and treated with a conservative strategy between 2012 and 2017 were included. The clinical risk model was based on the TIMI risk score using the following variables: age > 65 years, two episodes of angina or greater within the past 24 hours, electrocardiographic changes, coronary risk factors, history of coronary artery disease and previous aspirin, excluding high-sensitivity cardiac troponin T levels. The predictive value of high-sensitivity cardiac troponin was compared with the clinical risk model to predict in-hospital events using ROC curves. Combined inhospital events: recurrent angina, myocardial infarction and mortality High-sensitivity cardiac troponin T levels > 14 pg/ dL were considered elevated. Results: A total of 245 patients were included. Median age was 65 years (57-76) and 74% were men. Median clinical risk score was 3 (1-4) and 65% of the patients had elevated high-sensitivity cardiac troponin levels. In-hospital events: 55/245 patients (22.4%): recurrent angina, 20,4%; Q-wave myocardial infarction,1.6%; mortality, 0.4%. The prognostic accuracy of high-sensitivity cardiac troponin T to predict in-hospital events was 0.56 (0.48-0.65) compared with the clinical risk model [0.58 (0.49-0.67); p = 0.92] and the TIMI risk score (0.56; p: 0.16). Conclusions: In patients with non-ST segment elevation acute coronary syndrome, neither high-sensitivity cardiac troponinT levels nor clinical variables were consistent to predict in-hospital events. High-sensitivity cardiac troponin T levels used to guide the therapeutic strategy could lead to an unnecessary indication of procedures with the associated inherent risk.