Factors associated with disease progression in patients with atrial fibrillation and heart failure anticoagulated with rivaroxaban.

BACKGROUND: Patients with atrial fibrillation (AF) and heart failure (HF) have a high risk of thromboembolism and other outcomes and anticoagulation is recommended. HYPOTHESIS: This study was aimed to explore the risk factors associated with HF worsening in patients with AF and HF taking rivaroxaban in Spain. METHODS: Multicenter, prospective, observational study that included adults with AF and chronic HF, receiving rivaroxaban ≥4 months before entering. HF worsening was defined as first hospitalization or emergency visit because of HF exacerbation. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, mean age was 73.7 ± 10.9 years, 64.9% were male, CHA2 DS2 -VASc was 4.1 ± 1.5, HAS-BLED was 1.6 ± 0.9% and 51.3% had HF with preserved ejection fraction. After 24 months of follow-up, 24.9% of patients developed HF worsening, 11.6% died, 2.9% had a thromboembolic event, 3.1% a major bleeding, 0.5% an intracranial bleeding and no patient had a fatal hemorrhage. Older age, the history of chronic obstructive pulmonary disease, the previous use of vitamin K antagonists, and restrictive or infiltrative cardiomyopathies, were independently associated with HF worsening. Only 6.9% of patients permanently discontinued rivaroxaban treatment. CONCLUSIONS: Approximately one out of four patients with HF and AF treated with rivaroxaban developed a HF worsening episode after 2 years of follow-up. The identification of those factors that increase the risk of HF worsening could be helpful in the comprehensive management of this population.

Outcomes and factors associated with mortality in patients with atrial fibrillation and heart failure: FARAONIC study.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common and coexistent conditions. HYPOTHESIS: To investigate the adverse events and mortality risk factors in patients with AF and HF treated with rivaroxaban in Spain. METHODS: Multicenter, prospective and observational study with a follow-up of 2 years, that included adults, with a diagnosis of nonvalvular AF and chronic HF, anticoagulated with rivaroxaban at least 4 months before being enrolled. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, the mean age was 73.7 ± 10.9 years, 65.9% were male, 51.3% had HF with preserved ejection fraction and 58.7% were on New York Heart Association functional class II. CHA2 DS2 -VASc was 4.1 ± 1.5. During the follow-up, 11.6% of patients died and around one-quarter of patients were hospitalized or visited the emergency department, being HF worsening/progression the main cause (51.1%), with a 2.9% of thromboembolic events and 2.0% of acute coronary syndromes. Major bleeding occurred in 3.1% of patients, with 0.5% experiencing intracranial bleeding but no fatalities. Compliance with HF treatment was associated with a lower risk of death (hazard ratio: 0.092; 95% confidence interval: 0.03-0.31). CONCLUSIONS: Among patients with HF and AF anticoagulated with rivaroxaban, incidences of thromboembolic or hemorrhagic complications were low. The most important factor for improving survival was compliance with HF drugs, what strengths the need for early treatment with HF disease-modifying therapy and anticoagulation.

The Effects of a Therapeutic Strategy Guided by Lung Ultrasound on 6-Month Outcomes in Patients with Heart Failure: Results from the EPICC Randomized Controlled Trial.

Background: Pulmonary congestion (PC) is associated with an increased risk of hospitalization and death in patients with heart failure (HF). Lung ultrasound is highly sensitive for detecting PC. The aim of this study is to evaluate whether lung ultrasound-guided therapy improves 6-month outcomes in patients with HF. Methods: A randomized, multicenter, single-blind clinical trial in patients discharged after hospitalization for decompensated HF. Participants were assigned 1:1 to receive treatment guided according to the presence of lung ultrasound signs of congestion (semi-quantitative evaluation of B lines and the presence of pleural effusion) versus standard of care (SOC). The primary endpoint was the combination of cardiovascular death, readmission, or emergency department or day hospital visit due to worsening HF at 6 months. In September 2020, after an interim analysis, patient recruitment was stopped. Results: A total of 79 patients were randomized (mean age 81.2 +/− 9 years) and 41 patients (51.8%) showed a left ventricular ejection fraction >50%. The primary endpoint occurred in 11 patients (29.7%) in the SOC group and in 11 patients (26.1%) in the LUS group (log-rank = 0.83). Regarding nonserious adverse events, no significant differences were found. Conclusions: LUS-guided diuretic therapy after hospital discharge due to ADHF did not show any benefit in survival or a need for intravenous diuretics compared with SOC.

The organizing role of Wnt signaling pathway during arthropod posterior growth.

Wnt signaling pathways are recognized for having major roles in tissue patterning and cell proliferation. In the last years, remarkable progress has been made in elucidating the molecular and cellular mechanisms that underlie sequential segmentation and axial elongation in various arthropods, and the canonical Wnt pathway has emerged as an essential factor in these processes. Here we review, with a comparative perspective, the current evidence concerning the participation of this pathway during posterior growth, its degree of conservation among the different subphyla within Arthropoda and its relationship with the rest of the gene regulatory network involved. Furthermore, we discuss how this signaling pathway could regulate segmentation to establish this repetitive pattern and, at the same time, probably modulate different cellular processes precisely coupled to axial elongation. Based on the information collected, we suggest that this pathway plays an organizing role in the formation of the body segments through the regulation of the dynamic expression of segmentation genes, via controlling the caudal gene, at the posterior region of the embryo/larva, that is necessary for the correct sequential formation of body segments in most arthropods and possibly in their common segmented ancestor. On the other hand, there is insufficient evidence to link this pathway to axial elongation by controlling its main cellular processes, such as convergent extension and cell proliferation. However, conclusions are premature until more studies incorporating diverse arthropods are carried out.

Antígeno carbohidrato 125 (CA125) como marcador pronóstico en ancianos con insuficiencia cardiaca aguda y fracción de eyección preservada / Carbohydrate antigen 125 (CA125) as a prognostic marker in the elderly with acute heart failure and preserved ejection fraction

Antecedentes:El antígeno carbohidrato 125 (CA125) ha emergido como un nuevo biomarcador en insuficiencia cardiaca. El objetivo del estudio es determinar si los niveles séricos de CA125 predicen la mortalidad y reingresos totales a un año en pacientes mayores de 70 años e insuficiencia cardiaca aguda (ICA) con fracción de eyección preservada (FEP).Métodos:Estudio observacional prospectivo multicéntrico, que incluyó a 359 pacientes (edad media 81,5 años). La variable de valoración principal fue la mortalidad total por todas las causas y lo reingresos totales por ICA a un año. El análisis de regresión binomial negativa se utilizó para evaluar la asociación entre los valores de CA125 y el pronóstico.Resultados:Al año de seguimiento, se registraron 87 muertes (24,2%). Los pacientes del cuartil inferior de CA125 presentaron una tasa bruta de mortalidad menor (14,4%, 26,7, 26,7 y 29,2; p=0,090). Tras un análisis multivariado, el valor de CA125 se asoció de forma casi lineal y positiva a un mayor riesgo de mortalidad (p=0,009). Dicha asociación fue también positiva pero estadísticamente límite en el caso de los reingresos totales por ICA (p=0,089).Conclusiones:En población mayor de 70 años hospitalizada por ICA con FEP, los niveles elevados de CA125 se asocian a un aumento del riesgo de muerte a un año de seguimiento. La asociación con los reingresos fue más incierta. Los niveles bajos de CA125 identifica un subgrupo de pacientes de bajo riesgo. (AU)

Background:Carbohydrate antigen 125 (CA125) has emerged as a new biomarker in heart failure. The objective of the study is to determine whether serum CA125 levels predict total mortality and readmissions at one year in patients >70 years old with acute heart failure (AHF) and preserved ejection fraction (PEF).Methods:Multicenter prospective observational study, which included 359 patients (mean age 81.5 years). The primary endpoint was total all-cause mortality and total readmissions for AHF at 1 year. A negative binomial regression technique was used to evaluate the association between CA125 and both endpoints.Results:At one year of follow-up, 87 deaths (24.2%) were registered. The patients in the lower quartile of CA125 had a lower crude mortality rate (14.4%, 26.7, 26.7, 29.2; p=0.09). After multivariate analysis, the CA125 value was positively associated with a higher risk (p=0.009). Such association was also positive but borderline significant for the risk of readmissions (p=0.089).Conclusions:In a population older than 70 years hospitalized for AHF with PEF, elevated levels of CA125 are associated with an increased risk of death at one year of follow-up. The association with readmission for AHF was more uncertain. Low levels of CA125 identifies a subgroup at low-risk. (AU)

Vericiguat en insuficiencia cardíaca: de la evidencia científica a la práctica clínica / Vericiguat in heart failure: from scientific evidence to clinical practice

A pesar de los tratamientos actuales, el riesgo de muerte y hospitalizaciones en pacientes con insuficiencia cardíaca con fracción de eyección reducida (IC-FEr) sigue siendo elevado. La fisiopatología de la IC-FEr incluye activación neurohormonal caracterizada por la estimulación de las vías deletéreas (sistemas simpático y renina-angiotensina-aldosterona) y la supresión de las vías protectoras como las dependientes del óxido nítrico. La inhibición o estimulación de algunas de estas vías, pero no de todas, es insuficiente. En la IC-FEr existe una menor actividad de óxido nítrico, guanilato ciclasa soluble y GMPc que provoca efectos deletéreos a nivel miocárdico, vascular y renal. Vericiguat estimula la actividad de esta vía protectora. El estudio VICTORIA demostró, en pacientes con IC-FEr y descompensación reciente, que la adición de vericiguat al tratamiento médico óptimo reducía de forma significativa la incidencia del objetivo primario compuesto de muerte cardiovascular u hospitalización por IC, con un número de 24 pacientes que es necesario tratar, y una excelente tolerabilidad (AU)

Despite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability (AU)

T-cell activation and bacterial infection in skin wounds of recessive dystrophic epidermolysis bullosa patients.

Recessive dystrophic epidermolysis bullosa (RDEB) patients develop poorly healing skin wounds that are frequently colonized with microbiota. Because T cells play an important role in clearing such pathogens, we aimed to define the status of adaptive T cell-mediated immunity in RDEB wounds. Using a non-invasive approach for sampling of wound-associated constituents, we evaluated microbial contaminants in cellular fraction and exudates obtained from RDED wounds. Infectivity and intracellular trafficking of inactivated Staphylococcus aureus was accessed in RDEB keratinocytes. S. aureus and microbial antigen-specific activation of RDEB wound-derived T cells were investigated by fluorescence-activated cell sorting-based immune-phenotyping and T-cell functional assays. We found that RDEB wounds and epithelial cells are most frequently infected with Staphylococcus sp. and Pseudomonas sp. and that S. aureus essentially infects more RDEB keratinocytes and RDEB-derived squamous cell carcinoma cells than keratinocytes from healthy donors. The RDEB wound-associated T cells contain populations of CD4+ and CD8+ peripheral memory T cells that respond to soluble microbial antigens by proliferating and secreting interferon gamma (IFNγ). Moreover, CD8+ cytotoxic T lymphocytes recognize S. aureus-infected RDEB keratinocytes and respond by producing interleukin-2 (IL-2) and IFNγ and degranulating and cytotoxically killing infected cells. Prolonged exposure of RDEB-derived T cells to microbial antigens in vitro does not trigger PD-1-mediated T-cell exhaustion but induces differentiation of the CD4high population into CD4high CD25+ FoxP3+ regulatory T cells. Our data demonstrated that adaptive T cell-mediated immunity could clear infected cells from wound sites, but these effects might be inhibited by PD-1/Treg-mediated immuno-suppression in RDEB.

Vericiguat in heart failure: From scientific evidence to clinical practice.

Despite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability.

Diabetic cardiomyopathy.

The relationship between diabetes and heart failure is complex and bidirectional. Nevertheless, the existence of a cardiomyopathy attributable exclusively to diabetes has been and is still the subject of controversy, due, among other reasons, to a lack of a consensus definition. There is also no unanimous agreement in terms of the physiopathogenic findings that need to be present in the definition of diabetic cardiomyopathy or on its classification, which, added to the lack of diagnostic methods and treatments specific for this disease, limits its general understanding. Studies conducted on diabetic cardiomyopathy, however, suggest a unique physiopathogenesis different from that of other diseases. Similarly, new treatments have been shown to play a potential role in this disease. The following review provides an update on diabetic cardiomyopathy.

Evolución de la asociación de diabetes y eventos posalta en pacientes con insuficiencia cardíaca crónica descompensada: hallazgos del registro RICA / Changes over time in the association between type 2 diabetes and post-discharge outcomes in decompensated chronic heart failure patients: Findings from the RICA Registry

Objetivos: La insuficiencia cardíaca (IC) y la diabetes son 2procesos fuertemente asociados. El objetivo principal fue analizar la evolución del pronóstico de los pacientes con diabetes que ingresan por IC a lo largo de 2períodos. Métodos: Estudio prospectivo para comparar el pronóstico a un año de seguimiento entre los pacientes con diabetes que ingresan por IC en 2008-2011 y 2018. Los pacientes proceden del Registro Nacional de Insuficiencia Cardíaca (RICA) de la Sociedad Española de Medicina Interna. El objetivo primario fue analizar el desenlace combinado de mortalidad total o ingreso por IC durante 12 meses. Se utilizó una regresión multivariante de Cox para evaluar la fuerza de asociación (hazard ratio [HR]) de la diabetes y los desenlaces entre ambos períodos. resultados: Se incluyó a un total de 936 pacientes en la cohorte de 2018, de los que 446 (48%) tenían diabetes. Las características basales de la población de los 2períodos fueron similares. En los pacientes con diabetes se observó el desenlace combinado en 233 (47,5%) en la cohorte de 2008-2011 y 162 (36%) en la cohorte de 2018 (HR 1,48; intervalo de confianza del 95% [IC95%] 1,18-1,85; p <0,001). La proporción de ingresos (HR 1,39; IC95% 1,07-1,80; p=0,015) y la mortalidad total (HR 1,60; IC95% 1,20-2,14; p <0,001) también fueron significativamente mayores en los pacientes con diabetes de la cohorte de 2008-2011 con respecto a la del 2018. Conclusiones: En 2018 se observa una mejoría del pronóstico de la mortalidad total y los reingresos durante un año de seguimiento en pacientes con diabetes hospitalizados por IC con respecto al período de 2008-2011 (AU)

Aims: Heart failure (HF) and diabetes are 2strongly associated diseases. The main objective of this work was to analyze changes in the prognosis of patients with diabetes who were admitted for heart failure in 2time periods. Methods: This work is a prospective study comparing prognosis at one year of follow-up among patients with diabetes who were hospitalized for HF in either 2008-2011 or 2018. The patients are from the Spanish Society of Internal Medicine's National Heart Failure Registry (RICA, for its initials in Spanish). The primary endpoint was to analyze the composite outcome of total mortality and/or readmission due to HF in 12 months. A multivariate Cox regression model was used to evaluate the strength of association (hazard ratio [HR]) between diabetes and the outcomes between both periods. Results: A total of 936 patients were included in the 2018 cohort, of which 446 (48%) had diabetes. The baseline characteristics of the populations from the 2periods were similar. In patients with diabetes, the composite outcome was observed in 233 (47.5%) in the 2008-2011 cohort and 162 (36%) in the 2018 cohort [HR 1.48; 95% confidence interval (95%CI) 1.18-1.85; p<.001]. The proportion of readmissions (HR 1.39; 95%CI 1.07-1.80; p=.015) and total mortality (HR 1.60; 95%CI 1.20-2.14; p<.001) were also significantly higher in patients with diabetes from the 2008-2011 cohort compared to the 2018 cohort. Conclusions: In 2018, an improvement was observed in the prognosis for all-cause mortality and readmissions over one year of follow-up in patients with diabetes hospitalized for HF compared to the 2008-2011 period (AU)

Miocardiopatía diabética / Diabetic cardiomyopathy

La relación entre la diabetes y la insuficiencia cardiaca es compleja y bidireccional. No obstante, la existencia de una miocardiopatía como entidad propia y atribuible exclusivamente a la diabetes ha sido y es motivo de controversia hoy día. Esto es debido, entre otros motivos, a la ausencia de una definición de consenso. Tampoco existe unanimidad en cuanto a los hallazgos fisiopatogénicos presentes en la miocardiopatía diabética ni en su clasificación. Esto añadido a la ausencia de métodos diagnósticos propios o de tratamientos específicos en la enfermedad, limita el conocimiento general de la patología. Sin embargo, los estudios realizados en miocardiopatía diabética sugieren una fisiopatogenia propia diferenciada de la de otras entidades. De la misma manera, nuevos tratamientos han demostrado tener un papel potencial en esta enfermedad. En la siguiente revisión realizamos una actualización de la miocardiopatía diabética (AU)

The relationship between diabetes and heart failure is complex and bidirectional. Nevertheless, the existence of a cardiomyopathy attributable exclusively to diabetes has been and is still the subject of controversy, due, among other reasons, to a lack of a consensus definition. There is also no unanimous agreement in terms of the physiopathogenic findings that need to be present in the definition of diabetic cardiomyopathy or on its classification, which, added to the lack of diagnostic methods and treatments specific for this disease, limits its general understanding. Studies conducted on diabetic cardiomyopathy, however, suggest a unique physiopathogenesis different from that of other diseases. Similarly, new treatments have been shown to play a potential role in this disease. The following review provides an update on diabetic cardiomyopathy (AU)

Causas de muerte en pacientes hospitalizados en servicios de medicina interna por insuficiencia cardíaca según la fracción de eyección. Registro RICA / Causes of death in hospitalized patients in internal medicine departments with heart failure according to ejection fraction. RICA registry

IntroducciónLos datos disponibles de las causas de muerte en pacientes ingresados por insuficiencia cardíaca en servicios de medicina interna y en población española según fracción de eyección reducida (FER), preservada (FEP) e intermedia (FEI) son escasos. Su estudio puede mejorar el conocimiento de estos pacientes y su pronóstico.MétodosEstudio de cohortes multicéntrico y prospectivo de 4.144 pacientes que ingresaron por insuficiencia cardíaca en unidades de medicina interna. Se registraron sus características clínicas, tasa de fallecimientos y sus causas agrupadas según FEP (≥ 50%), FEI (40-49%) y FER (<40%) durante una mediana de seguimiento de un año.ResultadosSe registraron 1.198 fallecimientos (29%), de los que 833 fallecieron por causas cardiovasculares (69,5%), fundamentalmente por insuficiencia cardíaca (50%) y por muerte súbita (7,5%) y 365 por causas no cardiovasculares (NoCV) (30,5%), sobre todo por infecciones (13%). La causa más frecuente y temprana en todos los grupos fue la insuficiencia cardíaca. Los pacientes con FEP tenían menor tasa de muerte súbita y mayor de infecciones (p <0,05). Las causas de muerte en FEI fueron más parecidas a las de FEP.ConclusionesLas causas de muerte en pacientes con insuficiencia cardíaca fueron diferentes dependiendo del tipo de fracción de eyección. Los pacientes con FEI y FEP, por su elevada comorbilidad y mayor frecuencia de muerte NoCV, son los que más se beneficiarían de un manejo integral por parte de medicina interna.

Changes over time in the association between type 2 diabetes and post-discharge outcomes in decompensated chronic heart failure patients: Findings from the RICA Registry.

AIMS: Heart failure (HF) and diabetes are 2 strongly associated diseases. The main objective of this work was to analyze changes in the prognosis of patients with diabetes who were admitted for heart failure in 2 time periods. METHODS: This work is a prospective study comparing prognosis at one year of follow-up among patients with diabetes who were hospitalized for HF in either 2008-2011 or 2018. The patients are from the Spanish Society of Internal Medicine's National Heart Failure Registry (RICA, for its initials in Spanish). The primary endpoint was to analyze the composite outcome of total mortality and/or readmission due to HF in 12 months. A multivariate Cox regression model was used to evaluate the strength of association (hazard ratio [HR]) between diabetes and the outcomes between both periods. RESULTS: A total of 936 patients were included in the 2018 cohort, of which 446 (48%) had diabetes. The baseline characteristics of the populations from the 2 periods were similar. In patients with diabetes, the composite outcome was observed in 233 (47.5%) in the 2008-2011 cohort and 162 (36%) in the 2018 cohort [HR 1.48; 95% confidence interval (95%CI) 1.18-1.85; p < .001]. The proportion of readmissions (HR 1.39; 95%CI 1.07-1.80; p = .015) and total mortality (HR 1.60; 95%CI 1.20-2.14; p < .001) were also significantly higher in patients with diabetes from the 2008-2011 cohort compared to the 2018 cohort. CONCLUSIONS: In 2018, an improvement was observed in the prognosis for all-cause mortality and readmissions over one year of follow-up in patients with diabetes hospitalized for HF compared to the 2008-2011 period.

Causes of death in hospitalized patients in internal medicine departments with heart failure according to ejection fraction. RICA registry. / Causas de muerte en pacientes hospitalizados en servicios de medicina interna por insuficiencia cardíaca según la fracción de eyección. Registro RICA.

INTRODUCTION: There are few data in the Spanish population about the causes of death in patients admitted to internal medicine departments for heart failure. Their study according to left ventricular ejection fraction (reduced: rEF, mid-range: mEF, and preserved: pEF) could improve the knowledge of patients and their prognosis. METHODS: Prospective multicentre cohort study of 4144 patients admitted with heart failure to internal medicine departments. Their clinical characteristics, mortality rate and causes were classified according to pEF (≥ 50%), mEF (40%-49%) and rEF (<40%). Patients were followed-up for a median of one year. RESULTS: There were 1198 deaths (29%). The cause of death was cardiovascular (CV) in 833 patients (69.5%), mainly heart failure (50%) and sudden cardiac death (7.5%). Non-cardiovascular (NoCV) causes were responsible for 365 deaths (30.5%). The most common NoCV causes were infections (13%). The most frequent and early cause in all groups was heart failure. Patients with pEF, compared to the other groups, had lower risk of sudden cardiac death and higher risk of infections (P <.05). The causes of death in patients with mrEF were closer to those with pEF. CONCLUSIONS: The causes of death in patients with heart failure were different depending on ejection fraction strata. Patients with mEF and pEF, due to their high comorbidity and higher frequency of NoCV death, would require comprehensive management by internal medicine.

Carbohydrate antigen 125 (CA125) as a prognostic marker in the elderly with acute heart failure and preserved ejection fraction. / Antígeno carbohidrato 125 (CA125) como marcador pronóstico en ancianos con insuficiencia cardiaca aguda y fracción de eyección preservada.

BACKGROUND: Carbohydrate antigen 125 (CA125) has emerged as a new biomarker in heart failure. The objective of the study is to determine whether serum CA125 levels predict total mortality and readmissions at one year in patients >70 years old with acute heart failure (AHF) and preserved ejection fraction (PEF). METHODS: Multicenter prospective observational study, which included 359 patients (mean age 81.5 years). The primary endpoint was total all-cause mortality and total readmissions for AHF at 1 year. A negative binomial regression technique was used to evaluate the association between CA125 and both endpoints. RESULTS: At one year of follow-up, 87 deaths (24.2%) were registered. The patients in the lower quartile of CA125 had a lower crude mortality rate (14.4%, 26.7, 26.7, 29.2; p=0.09). After multivariate analysis, the CA125 value was positively associated with a higher risk (p=0.009). Such association was also positive but borderline significant for the risk of readmissions (p=0.089). CONCLUSIONS: In a population older than 70 years hospitalized for AHF with PEF, elevated levels of CA125 are associated with an increased risk of death at one year of follow-up. The association with readmission for AHF was more uncertain. Low levels of CA125 identifies a subgroup at low-risk.

Spatiotemporal variation in cell proliferation patterns during arthropod axial elongation.

An elongated and segmented body plan is a common morphological characteristic of all arthropods and is probably responsible for their high adaptation ability to diverse environments. Most arthropods form their bodies by progressively adding segments, resembling vertebrate somitogenesis. This sequential segmentation relies on a molecular clock that operates in the posterior region of the elongating embryo that combines dynamically with cellular behaviors and tissue rearrangements, allowing the extension of the developing body along its main embryonic axis. Even though the molecular mechanisms involved in elongation and segment formation have been found to be conserved in a considerable degree, cellular processes such as cell division are quite variable between different arthropods. In this study, we show that cell proliferation in the beetle Tribolium castaneum has a nonuniform spatiotemporal patterning during axial elongation. We found that dividing cells are preferentially oriented along the anterior-posterior axis, more abundant and posteriorly localized during thoracic segments formation and that this cell proliferation peak was triggered at the onset of axis elongation. This raise in cell divisions, in turn, was correlated with an increase in the elongation rate, but not with changes in cell density. When DNA synthesis was inhibited over this period, both the area and length of thoracic segments were significantly reduced but not of the first abdominal segment. We discuss the variable participation that different cell division patterns and cell movements may have on arthropod posterior growth and their evolutionary contribution.

Cognitive impairment in patients hospitalized for congestive heart failure: data from the RICA Registry.

The objective of this study is to determine the prevalence of cognitive impairment (CogI) in patients hospitalized for congestive heart failure, and the influence of CogI on mortality and hospital readmission. This is a multicenter cohort study of patients hospitalized for congestive heart failure enrolled in the RICA registry. The patients were divided into 3 groups according to their Short Portable Mental Status Questionnaire score: 0-3 errors (no CogI or mild CogI), 4-7 (moderate CogI) and 8-10 (severe CogI). A total of 3845 patients with a mean (SD) age of 79 (8.6) years were included; 2038 (53%) were women. A total of 550 (14%) patients had moderate CogI and 76 (2%) had severe CogI. Factors independently associated with severe CogI were age (OR 1.09, 95% CI 1.05-1.14 p < 0.001), male sex (OR 0.57, 95% CI 0.34-0.95, p = 0.031), heart rate (OR 1.01, 95% CI 1.00-1.02, p = 0.004), Charlson index (OR 1.16, 95% CI 1.06-1.27, p = 0.002), and history of stroke (OR 2.67, 95% CI 1.60-4.44, p < 0.001). Severe CogI was associated with higher mortality after one year (HR 3.05, 95% CI 2.25-4.14, p < 0.001). The composite variable of death/hospital readmission was higher in patients with CogI (log rank p < 0.001). Patients with heart failure and severe CogI are older and have a higher comorbidity burden, lower survival, and a higher rate of death or readmission at 1 year, compared to patients with no CogI.

Nutritional Risk and Mortality at One Year for Elderly Patients Hospitalized with Nonvalvular Atrial Fibrillation. Nonavasc Registry.

OBJECTIVES: To determine whether nutritional risk is associated with the mortality of elderly patients hospitalized with nonvalvular atrial fibrillation (NVAF). DESIGN: Prospective, multicenter cohort study. SETTING: Internal medicine departments in Spain. PARTICIPANTS: Inpatients >75 years with NVAF. MEASUREMENTS: We measured the thrombotic and hemorrhagic risk at admission using the CHA2DS2-VASc and HAS-BLED scales, respectively, and the nutritional risk with the controlling nutritional status (CONUT) index. We established 4 degrees of nutritional risk: null (CONUT score 0-1 point), low (2-4 points), moderate (5-8 points) and high (9-12 points). We also conducted a 1-year follow-up. RESULTS: We included 449 patients, with a mean age of 85.2(5.2) years. The nutritional risk was null for 70(15.6%) patients, low for 206 45.9%), moderate for 152(33.8%) and high for 21(4.7%). At the end of one year, 177(39.4%) patients had died. The score on the CONUT index was higher for the deceased patients (4.6 vs. 3.6, p<0.001). The CONUT score (HR, 1.076; 95%CI 1.009-1.148; p=0.025), the Charlson index (HR, 1.080; 95%CI 1.017-1.148; p=0.013) and the presence of pressure ulcers (HR, 1.700; 95%CI 1.028-2.810; p=0.039) were independently associated with increased mortality at one year of follow-up. The prescription of oral anticoagulants at discharge was associated with lower mortality (HR, 0.440; 95%CI 0.304-0.638; p<0.001). CONCLUSIONS: More than a third of elderly patients hospitalized with NVAF have a moderate to high nutritional risk. These patients have greater mortality at the end of one year.

Aberrant recruitment of leukocytes defines poor wound healing in patients with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Poorly healing wounds are one of the major complications in patients suffering from recessive dystrophic epidermolysis bullosa (RDEB). At present, there are no effective means to analyze changes in cellular and molecular networks occurring during RDEB wound progression to predict wound outcome and design betted wound management approaches. OBJECTIVES: To better define mechanisms influencing RDEB wound progression by evaluating changes in molecular and cellular networks. METHODS: We developed a non-invasive approach for sampling and analysis of wound-associated constituents using wound-covering bandages. Cellular and molecular components from seventy-six samples collected from early, established and chronic RDEB wounds were evaluated by FACS-based immuno-phenotyping and ELISA. RESULTS: Our cross-sectional analysis determined that progression of RDEB wounds to chronic state is associated with the accumulation (up to 90 %) of CD16+CD66b+ mature neutrophils, loss of CD11b+CD68+ macrophages, and a significant increase (up to 50 %) in a number of CD11c+CD80+CD86+ activated professional antigen presenting cells (APC). It was also marked by changes in activated T cells populations including a reduction of CD45RO+ peripheral memory T cells from 80 % to 30 % and an increase (up to 70 %) in CD45RA+ effector T cells. Significantly higher levels of MMP9, VEGF-A and cathepsin G were also associated with advancing of wounds to poorly healing state. CONCLUSIONS: Our data demonstrated that wound-covering bandages are useful for a non-invasive sampling and analysis of wound-associated constituents and that transition to poorly healing wounds in RDEB patients as associated with distinct changes in leukocytic infiltrates, matrix-remodeling enzymes and pro-angiogenic factors at wound sites.

Comorbilidad en pacientes con diabetes mellitus tipo 2 e insuficiencia cardíaca con fracción de eyección preservada. Análisis de clusters del registro RICA. Oportunidades de mejora / Comorbidity in patients with type 2 diabetes mellitus and heart failure with preserved ejection fraction. Cluster analysis of the RICA registry. Opportunities for improvement

ANTECEDENTES Y OBJETIVOS: La heterogeneidad de los pacientes con insuficiencia cardíaca y fracción de eyección preservada (ICFEP) es elevada, por lo que se tiende a agrupar en fenotipos para intervenir con precisión. Dentro de estos, los pacientes con diabetes mellitus (DM) mantienen esta heterogeneidad. Nuestro objetivo es describir grupos de pacientes con ICFEP y DM basados en otras comorbilidades. MATERIAL Y MÉTODOS: Los pacientes se reclutan desde el registro nacional de insuficiencia cardíaca (RICA). Se incluyen pacientes con fracción de eyección mayor o igual al 50% sin valvulopatía y con DM. Se realiza un análisis aglomerativo jerárquico con el método de Ward incluyendo las siguientes variables: dislipemia, hepatopatía, EPOC, demencia, enfermedad cerebrovascular, arritmia, presión arterial sistólica, índice de masa corporal (IMC), estimación del filtrado glomerular y hemoglobina. RESULTADOS: Se incluyen 1.934 pacientes con ICFEP, de los que 907 (46,9%) tenían DM, con predominio de mujeres (60,9%) y con un IMC de 31,1 (5,9) kg/m2. Se obtienen 4 grupos: dos con elevado riesgo vascular (uno con arritmia y otro no), con 263 pacientes el primero y 201 el segundo, otro con predominio de EPOC (140 pacientes) y un último grupo de 303 pacientes con más edad pero menos comorbilidad. CONCLUSIONES: En nuestros pacientes con ICFEP y DM predomina la obesidad y el sexo femenino. Los cuatro grupos ofrecen oportunidades de tratamiento para mejorar su pronóstico no solo basadas en la utilización de nuevos fármacos antidiabéticos sino por otras opciones que pueden suponer un punto de partida para nuevas investigaciones

AIM: The heterogeneity of patients with heart failure and preserved ejection fraction (HFpEF) is high, thusthis entity tends to be grouped into phenotypes to act with precision. Within these groups, patients with type 2 diabetes mellitus (T2DM) hold this heterogeneity. Our aim is to describe subgroups of patients with HFpEF and T2DM based on other comorbidities. MATERIAL AND METHODS: Patients were recruited from the national registry of heart failure (RCIA). Patients with ejection fraction greater than or equal to 50% without valvular disease and with T2DM were included. A hierarchical agglomerative analysis was performed with Ward's method including the following variables: dyslipidemia, liver disease, Chronic obstructive pulmonary disease (COPD), dementia, cerebrovascular disease, arrhythmia, systolic blood pressure, body mass index (BMI), estimation of glomerular filtration and hemoglobin. RESULTS: 1934 patients with ICFEP were included, of which 907 (46.9%) had T2DM with a predominance of women (60.9%) and with a BMI of 31.1 (5.9) Kg / m2. Four groups were obtained, two with high vascular risk (one with arrhythmia and the other without it) with 263 patients the first and 201 the second. A third group had a predominance of COPD (140 patients) and a last group with 303 patients older but with less comorbidity. CONCLUSIONS: In our patients with ICFEP and T2DM, obesity and female sex predominated. All four groups offered treatment chances to improve their prognosis not only based on the use of new antidiabetic drugs but also on other options that may be a starting point for further research