Outcomes after septal myectomy in a cohort of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract obstruction that doesn't improve with pharmacological management often requires septal myectomy. However, there are few centers with experience in the practice of this procedure in our country. We describe the clinical and echocardiographic characteristics and postoperative outcomes of patients with HCM indicated for septal myectomy at a reference center in Colombia. MATERIALS AND METHODS: Retrospective cohort study. Patients undergoing septal myectomy between 2010 and 2023 were included. Data were collected before and two years after surgery. RESULTS: 18 patients were included. The mean age was 50 years. The predominant functional class was NYHA II/III (94 %). Asymmetric septal variant (83.3 %) was the most frequent as well as obstructive phenotype (88.8 %). After myectomy, 70.5 % improved to NYHA I and 62.4 % had no significant gradient (<30 mmHg), and the most of patient improved SAM. One patient died post-procedure, anymore complications were presented. DISCUSSION/CONCLUSIONS: Septal myectomy is a safe procedure, with clinical and echocardiographic improvement, with low complication rates.

Steering the Microbiota-Gut-Brain Axis by Antibiotics to Model Neuro-Immune-Endocrine Disorders.

BACKGROUND: Over the last century, animal models have been employed to study the gut-brain axis and its relationship with physiological processes, including those necessary for survival, such as food intake and thermoregulation; those involved in diseases, ranging from inflammation to obesity; and those concerning the development of neurodegenerative diseases and neuropsychiatric disorders, such as Alzheimer's disease and autism spectrum disorder, respectively. SUMMARY: The gut microbiota has been recognized in the last decade as an essential functional component of this axis. Many reports demonstrate that the gut microbiota influences the development of a vast array of physiological processes. Experiments that use animal models to assess the effect of the gut microbiota on the brain and behavior may involve the acute or chronic administration of broad-spectrum antibiotics. KEY MESSAGES: This narrative review summarizes the beneficial or detrimental effects of antibiotics administered prenatally or postnatally to rodents during acute or chronic periods in a wide range of protocols. These include animal models of disease and behavioral paradigms of learning and memory, anxiety, obsessive-compulsive disorder, and autism spectrum disorder. Biomarkers and behavioral assays associated with antibiotic exposure are also included in this review.

Acute heart failure - an EFIM guideline critical appraisal and adaptation for internists.

BACKGROUND: Over the past two decades, several studies have been conducted that have tried to answer questions on management of patients with acute heart failure (AHF) in terms of diagnosis and treatment. Updated international clinical practice guidelines (CPGs) have endorsed the findings of these studies. The aim of this document was to adapt recommendations of existing guidelines to help internists make decisions about specific and complex scenarios related to AHF. METHODS: The adaptation procedure was to identify firstly unresolved clinical problems in patients with AHF in accordance with the PICO (Population, Intervention, Comparison and Outcomes) process, then conduct a critical assessment of existing CPGs and choose recommendations that are most applicable to these specific scenarios. RESULTS: Seven PICOs were identified and CPGs were assessed. There is no single test that can help clinicians in discriminating patients with acute dyspnoea, congestion or hypoxaemia. Performing of echocardiography and natriuretic peptide evaluation is recommended, and chest X-ray and lung ultrasound may be considered. Treatment strategies to manage arterial hypotension and low cardiac output include short-term continuous intravenous inotropic support, vasopressors, renal replacement therapy, and temporary mechanical circulatory support. The most updated recommendations on how to treat specific patients with AHF and certain comorbidities and for reducing post-discharge rehospitalization and mortality are provided. Overall, 51 recommendations were endorsed and the rationale for the selection is provided in the main text. CONCLUSION: Through the use of appropriate tailoring process methodology, this document provides a simple and updated guide for internists dealing with AHF patients.

Neurocysticercosis: The duration of its preclinical phase relies on the parasite location.

OBJECTIVES: Neurocysticercosis (NC) is a heterogeneous disease particularly in terms of response to treatment and prognosis. Parasite localization is one of the main factors involved in this heterogeneity. In this study we aim to determine whether differences in the duration of the preclinical phase associated with parasite location, could contribute to said heterogeneity. METHODS: Ninety-nine patients were included, 24 with parasites in the parenchyma (PAR), 56 in the subarachnoid (SA) space and 19 in the ventricular system (IV). A questionnaire designed to assess exposure to classic NC risk factors 5, 10, 15, 20 and more than 20 years prior to diagnosis was applied. The results were compared between the three groups. Also, asymptomatic relatives of patients who had shared their living conditions in childhood or more recently were included and underwent brain scan and blood testing for specific antibodies. RESULTS: Over the course of their lives, exposure to risk factors decreased significantly for all patients, although the decrease was more evident in patients with parasites in the SA space (p < 0.001) compared to patients with PAR (p = 0.011) or IV cysts (p = 0.020). Five years prior to diagnosis, exposure to risk factors was significantly higher in patients with PAR or IV NC than in patients with SA NC (p = 0.04). Furthermore, individuals in close contact with PAR or IV patients in the years preceding diagnosis were more likely to have asymptomatic NC, specific antibodies in sera, particularly IgM, compared to individuals in close contact with SA patients during the same period. CONCLUSIONS: All these findings are highly suggestive of the possibility of a more recent infection of patients affected by parenchymal and ventricular NC than of patients with subarachnoid NC. Consequently, subarachnoid disease could be considered a chronic disease, which, probably contributes to the severity of the disease as well as the minimal response to medical treatment.

Application of eligibility criteria from DAPA-HF, EMPEROR-Reduced, and PARADIGM-HF trials to a population with heart failure with reduced ejection fraction at a specialized cardiology Clinic in Medellin, Colombia: A retrospective cohort study.

INTRODUCTION: The evidence supporting pharmacological heart failure treatment relies on randomized clinical trials with stringent inclusion and exclusion criteria. OBJECTIVES: Assess the eligibility of outpatients with chronic heart failure for the trials DAPA-HF, EMPEROR-reduced, and PARADIGM-HF, while exploring potential differences among study populations. METHODS: By reviewing medical records, we determined the eligibility rate for each study and evaluated the incidence of heart failure hospitalizations and all-cause mortality during this period. RESULTS: A total of 446 patients were included in the cohort. Approximately 75% would be ineligible for the trials, mainly because of their comorbidities. Ineligible patients had a higher all-cause mortality, but a similar incidence of hospitalization. CONCLUSION: Approximately 1 in 4 patients from a heart failure clinic in Medellin, Colombia would meet the eligibility criteria for the DAPA-HF, EMPEROR-reduced, and PARADIGM-HF trials. These findings highlight the need to complement randomized clinical trials with real-world data.

Prognostic Impact of the UMIPIC Program in the Follow Up in Patients with Heart Failure and Cardiorenal Syndrome.

BACKGROUND: Individuals suffering from heart failure (HF) and cardiorenal syndrome (CRS) represent a special group of patients considering their age, multiple health issues, and treatment challenges. These factors make them more susceptible to frequent hospital stays and a higher mortality rate. UMIPIC is a multidisciplinary care model program for patients with heart failure follow up provided by internists and nurses who are experts in this entity. Our study delved into the effectiveness of this specialized care program (UMIPIC) in mitigating these risks for HF and CRS patients. METHODS: We analyzed the medical records of 3255 patients diagnosed with HF and CRS types 2 and 4, sourced from the RICA registry. These patients were divided into two distinct groups: those enrolled in the UMIPIC program (1205 patients) and those under standard care (2050 patients). Using propensity score matching, we ensured that both groups were comparable. The study focused on tracking hospital admissions and mortality rates for one year after an HF-related hospital stay. RESULTS: Patients in the UMIPIC group experienced fewer hospital readmissions due to HF compared to their counterparts (20% vs. 32%; Hazard Ratio [HR] = 0.48; 95% Confidence Interval [95% CI]: 0.40-0.57; p < 0.001). They also showed a lower mortality rate (24% vs. 36%; HR = 0.64; 95% CI: 0.54-0.75; p < 0.001). Furthermore, the UMIPIC group had fewer total hospital admissions (36% vs. 47%; HR = 0.58; 95% CI: 0.51-0.66; p < 0.001). CONCLUSIONS: The UMIPIC program, centered on holistic and ongoing care, effectively reduces both hospital admissions and mortality rates for HF and CRS patients after a one-year follow-up period.

Resumen ejecutivo de la actualización 2023 del consenso de actuación básica durante el ingreso hospitalario por insuficiencia cardiaca aguda / Executive summary of the 2023 update on the consensus regarding basic conduct during hospital admission for patients with acute heart failure

La insuficiencia cardiaca aguda (ICA) está asociada a una importante morbimortalidad, constituyendo la primera causa de hospitalización en mayores de 65 años en nuestro país. Las principales recomendaciones recogidas son: 1) al ingreso, se recomienda realizar una evaluación integral, considerando el tratamiento habitual y comorbilidades, ya que condicionan el pronóstico; 2) en las primeras horas de atención hospitalaria, el tratamiento descongestivo es prioritario, y se recomienda un abordaje terapéutico diurético precoz y escalonado en función de la respuesta; 3) durante la fase estable, se recomienda considerar el inicio y/o titulación del tratamiento con fármacos basados en la evidencia, es decir, sacubitrilo/valsartán o inhibidores de la enzima convertidora de angiotensina/antagonistas de los receptores de angiotensina II, betabloqueantes, antialdosterónicos e inhibidores SGLT2, y 4) en el momento del alta hospitalaria, es recomendable utilizar un listado —tipo check-list— para optimizar el manejo del paciente hospitalizado e identificar las opciones más eficientes para mantener la continuidad de cuidados tras el alta (AU)

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease; (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response; (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors; (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge (AU)

Manejo y tratamiento actual de la insuficiencia cardiaca en unidades acreditadas de cardiología y medicina interna en España / Current heart failure disease management and treatment in accredited units from cardiology and internal medicine in Spain

Antecedentes y objetivos La insuficiencia cardiaca (IC) es una patología compleja con una alta prevalencia, incidencia y mortalidad que conlleva un importante coste sanitario. En España existen unidades de IC (UIC) multidisciplinares, lideradas por cardiología y medicina interna. Nuestro objetivo era conocer su organización actual y adherencia a las últimas recomendaciones científicas. Materiales y métodos Un comité científico formado por cardiólogos e internistas elaboró una encuesta a finales de 2021, que fue enviada a 110 UIC. Setenta y tres de cardiología, acreditadas por SEC-Excelente, y 37 de medicina interna, integradas en el programa UMIPIC. Resultados Se recibieron 83 encuestas cumplimentadas (75,5%); 49 de cardiología y 34 de medicina interna. Los resultados mostraron que las UIC están integradas mayoritariamente por un cardiólogo, internista y enfermería especializada (34,9%). El perfil de paciente atendido en las UIC cardiológicas es muy diferente al paciente de las UMIPIC, siendo estos últimos mayores, con fracción de eyección ventricular izquierda conservada y más carga de comorbilidad. La mayoría de UIC actualmente realizan seguimiento mixto, presencial y telemático (73,5%). Los péptidos natriuréticos son los biomarcadores más utilizados (90%). Se titulan los cuatro grupos farmacológicos fundamentales de tratamiento de la IC a la vez mayoritariamente (85%). Solo 24% de las unidades mantienen una comunicación fluida con atención primaria. Conclusiones Los dos modelos de UIC liderados por cardiología y medicina interna son complementarios, disponen de enfermería especializada, y siguen al paciente de forma mixta, con una adherencia farmacológica muy alta a las últimas recomendaciones científicas. El principal punto de mejora es la coordinación con atención primaria (AU)

Background and objectives Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective was to describe its current organizational model and their adherence to the latest scientific recommendations. Materials and methods In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units [73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine (integrated in UMIPIC program)]. Results We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. Conclusions Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area (AU)

Executive summary of the 2023 update on the consensus regarding basic conduct during hospital admission for patients with acute heart failure.

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) Upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease. (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response. (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors. (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge.

Benefits of dapagliflozin in the whole spectrum of heart failure in clinical practice: the RICA registry.

Aims: To determine the projected benefits of dapagliflozin after an acute heart failure (HF) event in Spain. Methods: A multicenter and prospective study that included subjects aged 50 years or older consecutively admitted with HF to internal medicine departments in Spain. The projected clinical benefits of dapagliflozin were calculated via pooled analysis of the DAPA-HF and DELIVER trials. Results: A total of 5644 subjects were analyzed, of whom 79.2% were eligible for dapagliflozin, according to criteria of the DAPA-HF and DELIVER trials. Full implementation of dapagliflozin would imply a 1-year absolute risk reduction of 2.3% for death (number needed to treat = 43) and 5.7% (number needed to treat = 17) for HF rehospitalization. Conclusion: Treatment with dapagliflozin could significantly reduce HF burden in clinical practice.

Heart failure is a severe condition that is associated with a high risk of complications. This means that it is important to start using new therapies that have demonstrated a clinical benefit. Clinical trials have shown that dapagliflozin reduces the risk of developing these complications in patients with heart failure. However, it is important to find out whether the results of clinical trials are also seen in real-life populations. We estimated the potential benefits of dapagliflozin in people admitted to hospital more than once with heart failure. The study took place in Spain. Our data suggest that treatment with dapagliflozin could reduce the complications associated with heart failure in real-life patients.

Projected clinical benefits of dapagliflozin in patients with heart failure with preserved ejection fraction.

Aims: To address the projected clinical benefits of dapagliflozin among patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF). Methods: A multicenter, prospective, cohort study of patients ≥50 years admitted with HF to Spanish internal medicine departments. The projected clinical benefits of dapagliflozin were calculated from the DELIVER trial. Results: A total of 4049 patients were included; 3271 (80.8%) were eligible for dapagliflozin treatment, according to DELIVER criteria. Within 1 year after discharge, 22.2% were rehospitalized for HF and 21.6% died. Implementation of dapagliflozin would translate into an absolute risk reduction of 1.3% for mortality and 5.1% for HF readmission. Conclusion: HF patients with preserved or mildly reduced ejection fraction have a high risk of events. The use of dapagliflozin could substantially reduce the HF burden.

Heart failure (HF) with preserved ejection fraction is frequent in clinical practice, particularly in the elderly. In HF with preserved ejection fraction, the heart still pumps a similar proportion of blood, but the heart muscle has become thicker. This means there is less space inside the heart to fill with blood, so too little is pumped out each time. Until very recently, no drugs had been shown to provide significant benefits on the outcome of the condition or the chance of recovery for these patients. Fortunately, recent clinical trials have demonstrated that treatment with drugs called SGLT2 inhibitors (e.g., dapagliflozin) could reduce the chance of being admitted to hospital or dying from HF. We investigated the benefits for patients who took dapagliflozin after being admitted to hospital and had HF with mildly reduced or preserved ejection fraction. We saw substantial benefits in this population.

Projected effectiveness of dapagliflozin in heart failure with reduced ejection fraction in clinical practice.

Aim: To estimate the projected effectiveness of dapagliflozin in subjects with heart failure (HF) with reduced ejection fraction in clinical practice in Spain. Materials & methods: This multicenter cohort study included subjects aged 50 years or older consecutively hospitalized for HF in internal medicine departments in Spain. The projected clinical benefits of dapagliflozin were estimated based on results from the DAPA-HF trial. Results: A total of 1595 patients were enrolled, of whom 1199 (75.2%) were eligible for dapagliflozin. Within 1 year after discharge, 21.6% of patients eligible for dapagliflozin were rehospitalized for HF and 20.5% died. Full implementation of dapagliflozin led to an absolute risk reduction of 3.5% for mortality (number needed to treat = 28) and 6.5% (number needed to treat = 15) for HF readmission. Conclusion: Treatment with dapagliflozin in clinical practice may markedly reduce mortality and readmissions for HF.

Heart failure with reduced ejection fraction is a severe disease with a high risk of hospitalization and mortality. With this condition, the heart muscle cannot pump properly. This means that not enough blood is pumped from the heart, reducing the amount of oxygen to the body. Fortunately, there are treatments that reduce this risk, in patients with heart failure. SGLT2 inhibitors, including dapagliflozin, are among the first therapies given to patients with heart failure. In this study, we investigated the potential benefits of adding dapagliflozin to the treatment of patients admitted to the hospital in Spain for heart failure with reduced ejection fraction. Our data showed that dapagliflozin was able to reduce the risk of further events (e.g., heart attack) in these patients.

Current heart failure disease management and treatment in accredited units from cardiology and internal medicine in Spain.

BACKGROUND AND OBJECTIVES: Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective is to describe its current organizational model and their adherence to the latest scientific recommendations. MATERIALS AND METHODS: In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units. 73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine, (integrated in UMIPIC program). RESULTS: We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. CONCLUSIONS: Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area.

Introducción de biosimilares anti-TNF e impacto económico en un hospital de tercer nivel / Introduction of anti-TNF biosimilars and economic impact in a third level hospital

Objetivos: Analizar la introducción de medicamentos biosimilares anti-TNF en primera línea para pacientes con artritis reumatoide (AR). Métodos: Estudio unicéntrico, retrospectivo y observacional en un hospital de tercer nivel. Se incluyeron pacientes con diagnóstico de AR tratados por primera vez con un fármaco biológico (biosimilar u original), entre febrero 2017-febrero 2021. Las variables de resultado recogidas fueron: porcentaje de pacientes que iniciaban tratamiento cada año con cada fármaco biológico y porcentaje de variación anual de utilización de fármacos anti-TNF que tenían biosimilar respecto al resto de alternativas. Resultados: 178 pacientes con diagnóstico de AR fueron tratados por primera vez con un fármaco biológico. Durante los dos primeros años de introducción de biosimilares, el porcentaje de pacientes con AR tratados en primera línea con adalimumab, infliximab y etanercept fue 23,9%, mientras que los dos últimos años aumentaron las prescripciones con estos fármacos, a pesar de la aparición de nuevos originales, de forma que durante el último año de estudio cubrían un 44,6% de las prescripciones. El uso de estos tres fármacos anti-TNF biosimilares en pacientes con AR ha supuesto un ahorro de 213.530 €. Conclusiones: En nuestro centro el uso de biosimilares anti-TNF se ha consolidado en los dos últimos años, a pesar de la incorporación de nuevos originales en el tratamiento de la AR. Considerando las diferentes políticas de introducción de biosimilares existentes, sería interesante que se realizarán estudios similares en otras regiones de nuestro país para poder establecer que política de uso de biosimilares puede ser más aceptada. (AU)

Objectives: To analyze the introduction of first-line anti-TNF biosimilar drugs for patients with rheumatoid arthritis (RA). Methods: Single-center, retrospective, observational study in a tertiary hospital. Patients with a diagnosis of RA treated for the first time with a biologic drug (biosimilar or original) between February 2017-February 2021 were included. The outcome variables collected were: percentage of patients initiating treatment each year with each biologic drug and percentage of annual variation in the use of anti-TNF drugs that had a biosimilar with respect to the other alternatives. Results: 178 patients diagnosed with RA were treated for the first time with a biologic drug. During the first two years of the introduction of biosimilars, the percentage of RA patients treated first line with adalimumab, infliximab and etanercept was 23.9%, while in the last two years prescriptions with these drugs increased, despite the appearance of new originals, so that during the last year of the study they covered 44.6% of prescriptions. The use of these three biosimilar anti-TNF drugs in patients with RA has resulted in savings of 213,530 €. Conclusions: In our center, the use of anti-TNF biosimilars has been consolidated in the last two years, despite the incorporation of new originals in the treatment of RA. Considering the different existing biosimilar introduction policies, it would be interesting to carry out similar studies in other regions of our country in order to establish which biosimilar use policy may be more accepted. (AU)

Identifying the patient with heart failure to be treated with vericiguat.

The pathophysiology of heart failure with reduced ejection fraction (HFrEF) is a complex process in which a number of neurohormonal systems are involved. Targeting only some of these systems, but not all, translates into a partial benefit of HF treatment. The nitric oxide-soluble guanylate cyclase (sGC)-cGMP pathway is impaired in HF, leading to cardiac, vascular and renal disturbances. Vericiguat is a once-daily oral stimulator of sGC that restores this system. No other disease-modifying HF drugs act on this system. Despite guidelines recommendations, a substantial proportion of patients are not taking all recommended drugs or when taking them, they do so at low doses, limiting their potential benefits. In this context, treatment should be optimized considering different parameters, such as blood pressure, heart rate, renal function, or potassium, as they may interfere with their implementation at the recommended doses. The VICTORIA trial showed that adding vericiguat to standard therapy in patients with HFrEF significantly reduced the risk of cardiovascular death or HF hospitalization by 10% (NNT 24). Furthermore, vericiguat does not interfere with heart rate, renal function or potassium, making it particularly useful for improving the prognosis of patients with HFrEF in specific settings and clinical profiles.

Optimizing the management of patients with worsening heart failure: beyond heart failure hospitalization.

INTRODUCTION: Worsening heart failure (HF) is associated with a high risk of death and HF hospitalization. AREAS COVERED: A systematic search was conducted on PubMed (MEDLINE), using the MeSH terms [Heart failure] + [Worsening] + [Treatment] + [Vulnerable period] up to February 2023. Original data from clinical trials, and observational studies were critically analyzed. EXPERT OPINION: Although the vulnerable period has been traditionally limited to the first 6 months after HF hospitalization, the fact is that there are other clinical scenarios in which the patient is particularly vulnerable. These vulnerable patients may also include those that require parenteral administration of diuretics in the day hospital or emergency department, those in which the increase of oral diuretic dose in an outpatient setting is needed to relief congestive symptoms, as well as those that remain symptomatic despite treatment. On the other hand, HF is a complex disease in which different neurohormonal systems are involved. Therefore, to actually reduce the HF burden, a comprehensive management, targeting all the neurohormonal systems that are involved in the pathogenesis of HF, through the use of those drugs that have demonstrated to positively modify the clinical course of HF, is needed.

The influence of comorbidities on the prognosis after an acute heart failure decompensation and differences according to ejection fraction: Results from the EAHFE and RICA registries.

OBJECTIVE: The role of comorbidities in heart failure (HF) outcome has been previously investigated, although mostly individually. We investigated the individual effect of 13 comorbidities on HF prognosis and looked for differences according to left-ventricular ejection fraction (LVEF), classified as reduced (HFrEF), mildly-reduced (HFmrEF) and preserved (HFpEF). METHODS: We included patients from the EAHFE and RICA registries and analysed the following comorbidities: hypertension, dyslipidaemia, diabetes mellitus (DM), atrial fibrillation (AF), coronary artery disease (CAD), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), heart valve disease (HVD), cerebrovascular disease (CVD), neoplasia, peripheral artery disease (PAD), dementia and liver cirrhosis (LC). Association of each comorbidity with all-cause mortality was assessed by an adjusted Cox regression analysis that included the 13 comorbidities, age, sex, Barthel index, New York Heart Association functional class and LVEF and expressed as adjusted Hazard Ratios (HR) with 95% confidence intervals (95%CI). RESULTS: We analysed 8,336 patients (82 years-old; 53% women; 66% with HFpEF). Mean follow-up was 1.0 years. Respect to HFrEF, mortality was lower in HFmrEF (HR:0.74;0.64-0.86) and HFpEF (HR:0.75;0.68-0.84). Considering patients all together, eight comorbidities were associated with mortality: LC (HR:1.85;1.42-2.42), HVD (HR:1.63;1.48-1.80), CKD (HR:1.39;1.28-1.52), PAD (HR:1.37;1.21-1.54), neoplasia (HR:1.29;1.15-1.44), DM (HR:1.26;1.15-1.37), dementia (HR:1.17;1.01-1.36) and COPD (HR:1.17;1.06-1.29). Associations were similar in the three LVEF subgroups, with LC, HVD, CKD and DM remaining significant in the three subgroups. CONCLUSION: HF comorbidities are associated differently with mortality, LC being the most associated with mortality. For some comorbidities, this association can be significantly different according to the LVEF.

Intense inhibitory avoidance training increases nuclear-phosphorylated glucocorticoid receptors in neurons of CA1 of hippocampus and ventral caudate putamen.

Corticosterone (CORT), the principal glucocorticoid in rodents, is released after stressful experiences such as training with high foot-shock intensities in the inhibitory avoidance task (IA). CORT reaches the glucocorticoid receptor (GR) located in almost all brain cells; the GR is subsequently phosphorylated at serine 232 (pGRser232). This has been reported as an indicator of ligand-dependent activation of the GR, as well as a requirement for its translocation into the nucleus for its transcription factor activity. The GR is present in the hippocampus with a high concentration in CA1 and dentate gyrus (DG), and a smaller proportion in CA3, and sparsely present in the caudate putamen (CPu); both structures are involved in memory consolidation of IA. To study the participation of CORT in IA, we quantified the ratio of pGR-positive neurons in both dorsal hippocampus (CA1, CA3 and DG) and dorsal and ventral regions of CPu of rats trained in IA, using different foot-shock intensities. Brains were dissected 60 min after training for immunodetection of pGRser232 positive cells. The results show that the groups trained with 1.0 and 2.0 mA had higher retention latencies than the 0.0 mA or 0.5 mA groups. An increase in the ratio of pGR-positive neurons was found in CA1 and ventral region of CPu only for the 2.0 mA trained group. These findings suggest that activation of GRs in CA1 and ventral CPu is involved in the consolidation of a stronger memory of IA, possibly through the modulation of gene expression.

Pepper growth promotion and biocontrol against Xanthomonas euvesicatoria by Bacillus cereus and Bacillus thuringiensis formulations.

Background: Bacillus genus has been used in horticultural crops as a biocontrol agent against insect pests, microbial phytopathogens, and plant growth-promoting bacteria (PGPB), representing an alternative to agrochemicals. In particular, B. cereus (Bc) and B. thuringiensis (Bt) have been studied for their fungicidal and insecticidal activities. However, their use as biofertilizer formulations and biocontrol agents against phytopathogenic bacteria is limited. Objective: To evaluate Bc and Bt formulations as PGPB and biocontrol agents against the bacterial spot agent Xanthomonas euvesicatoria (Xe) in greenhouse-grown chili peppers. Methods: Bc and Bt isolates obtained from soil samples were identified and characterized using conventional biochemical and multiplex PCR identification methods. Bioassays to determine Bc and Bt isolates potential as PGPB were evaluated on chili pepper seedlings in seedbeds. In addition, formulations based on Bc (F-BC26 and F-BC08) and Bt (F-BT24) strains were assessed as biofertilizers on pepper, under controlled conditions. Furthermore, in vitro antagonism assays were performed by confronting Bc and Bt isolate formulations against Xe isolates in direct (foliage) and indirect (resistance induction) phytopathogen biocontrol assays on pepper plants, which were grown under controlled conditions for 15 d after formulations treatment. Results: Isolates were identified as Bc and Bt. Formulations significantly improved pepper growth in seedbeds and pots, whereas in vitro bioassays demonstrated the bactericidal effect of Bc and Bt strains against Xe isolates. Furthermore, assays showed significant plant protection by F-BC26, F-BC08, and F-BT24 formulated strains against Xe. Conclusion: Results indicated that F-BT24 and F-BC26 isolates formulations promoted pepper growth and protected it against Xanthomonas euvesicatoria.

Enhanced efficiency in visually guided online motor control for actions redirected towards the body midline.

Reaching objects in a dynamic environment requires fast online corrections that compensate for sudden object shifts or postural changes. Previous studies revealed the key role of visually monitoring the hand-to-target distance throughout action execution. In the current study, we investigate how sensorimotor asymmetries associated with space perception, brain lateralization and biomechanical constraints, affect the efficiency of online corrections. Participants performed reaching actions in virtual reality, where the virtual hand was progressively displaced from the real hand to trigger online corrections, for which it was possible to control the total amount of the redirection and the region of space in which the action unfolded. The efficiency of online corrections and the degree of awareness of the ensuing motor corrections were taken as assessment variables. Results revealed more efficient visuo-motor corrections for actions redirected towards, rather than away from the body midline. The effect is independent on the reaching hand and the hemispace of action, making explanations associated with laterality effects and biomechanical constraints improbable. The result cannot either be accounted for by the visual processing advantage in the straight-ahead region. An explanation may be found in the finer sensorimotor representations characterizing the frontal space proximal to body, where a preference for visual processing has been documented, and where high-value functional actions, like fine manipulative skills, typically take place. This article is part of a discussion meeting issue 'New approaches to 3D vision'.