Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial.

OBJECTIVE: Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone. METHODS: In this substudy (n=290) to the Heart 'Omics' in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher's Z transform. RESULTS: Multivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66-95) to 75 (61-90) µg/L and PICP/CITP from 22 (17-28) to 18 (13-26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of -0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio. CONCLUSIONS: Spironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs. TRIAL REGISTRATION NUMBER: NCT02556450.

Sufficiency for PSS tracking gait disorders in multiple sclerosis: A managerial perspective.

This study primarily aimed to explore the capabilities of digitalisation in the healthcare context, focusing on a specific disease. In this case, the study examined the potential of remote monitoring of gait to address the sensitivity of multiple sclerosis progression to gait characteristics by adopting a non-invasive approach to remotely quantify gait disturbances in a patient's daily life. To better understand the managerial aspects associated with this approach, the researchers conducted a literature review along with a set of semi-structured interviews. The target population included MS patients as well as the key agents involved in their care: patients' family members, neurologists, MS nurses, physiotherapists, medical directors, and pharmacist. The study identifies the perceived barriers and drivers that could contribute to the successful deployment of PSS remote gait monitoring as a healthcare service: i) At mega-level governance. Implications on privacy and security data are notable barriers missing on the speech. ii) At macro level, funding is highlighted as main barrier. The cost and lack of health system subsidies may render initiatives unsustainable, as emphasised by the interviewees. iii) At meso level, useable data is recognised as a driver. The data collection process can align with diverse interests to create value and business opportunities for the ecosystem actors, enhance care, attract stakeholders, such as insurers and pharma, and form partnerships. iv) At micro-level processes, we find two potential barriers: wearable device and app usability (comfort, navigation, efficiency) and organisational/behavioural aspects (training, digital affinity, skills), which are crucial for value creation in innovation ecosystems among patients and healthcare professionals. Finally, we find an interesting gap in the literature and interviews. Stakeholders' limited awareness of technological demands, especially from information technologies, for a successful long-term service, can be consider two key barriers for PSS.

Possible Role of Gut Microbiota Alterations in Myocardial Fibrosis and Burden of Heart Failure in Hypertensive Heart Disease.

Epidemiological studies have revealed that hypertensive heart disease is a major risk factor for heart failure, and its heart failure burden is growing rapidly. The need to act in the face of this threat requires first an understanding of the multifactorial origin of hypertensive heart disease and second an exploration of new mechanistic pathways involved in myocardial alterations critically involved in cardiac dysfunction and failure (eg, myocardial interstitial fibrosis). Increasing evidence shows that alterations of gut microbiota composition and function (ie, dysbiosis) leading to changes in microbiota-derived metabolites and impairment of the gut barrier and immune functions may be involved in blood pressure elevation and hypertensive organ damage. In this review, we highlight recent advances in the potential contribution of gut microbiota alterations to myocardial interstitial fibrosis in hypertensive heart disease through blood pressure-dependent and blood pressure-independent mechanisms. Achievements in this field should open a new path for more comprehensive treatment of myocardial interstitial fibrosis in hypertensive heart disease and, thus, for the prevention of heart failure.

Multidisciplinary Management of Patients With Chronic Obstructive Pulmonary Disease and Cardiovascular Disease

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist, increasing the prevalence of both entities and impacting on symptoms and prognosis. CVD should be suspected in patients with COPD who have high/very high risk scores on validated scales, frequent exacerbations, precordial pain, disproportionate dyspnea, or palpitations. They should be referred to cardiology if they have palpitations of unknown cause or angina pain. COPD should be suspected in patients with CVD if they have recurrent bronchitis, cough and expectoration, or disproportionate dyspnea. They should be referred to a pulmonologist if they have rhonchi or wheezing, air trapping, emphysema, or signs of chronic bronchitis. Treatment of COPD in cardiovascular patients should include long-acting muscarinic receptor antagonists (LAMA) or long-acting beta-agonists (LABA) in low-risk or high-risk non-exacerbators, and LAMA/LABA/inhaled corticosteroids in exacerbators who are not controlled with bronchodilators. Cardioselective beta-blockers should be favored in patients with CVD, the long-term need for amiodarone should be assessed, and antiplatelet drugs should be maintained if indicated. (AU)

Influence of diabetes and other risk factors on in-hospital mortality following kidney transplantation: an analysis of the Spanish National Hospital Discharge Database from 2016 to 2020.

INTRODUCTION: To assess time trends in incidence, clinical characteristics, complications, and hospital outcomes among patients with type 1 diabetes (T1D), with type 2 diabetes (T2D), and patients without diabetes who underwent kidney transplant (KT); to identify variables associated with in-hospital mortality (IHM); and to determine the impact of the COVID-19 pandemic. RESEARCH DESIGN AND METHODS: We used a nationwide discharge database to select KT recipients admitted to Spanish hospitals from 2016 to 2020. We stratified patients according to diabetes status. We used multivariable logistic regression to identify the variables associated with IHM. RESULTS: A total of 14 594 KTs were performed in Spain (T2D, 22.28%; T1D, 3.72%). The number of KTs rose between 2016 and 2019 and and decreased from 2019 to 2020 in all groups. In patients with T2D, the frequency of KT complications increased from 21.08% in 2016 to 34.17% in 2020 (p<0.001). Patients with T2D had significantly more comorbidity than patients with T1D and patients without diabetes (p<0.001). Patients with T1D experienced KT rejection significantly more frequently (8.09%) than patients with T2D (5.57%).COVID-19 was recorded in 26 out of the 2444 KTs performed in 2020, being found in 6 of the 39 patients deceased that year (15.38%) and in 0.83% of the survivors.The variables associated with IHM were comorbidity and complications of KT. The presence of T1D was associated with IHM (OR 2.6; 95% CI 1.36 to 5.16) when patients without diabetes were the reference category. However, T2D was not associated with a higher IHM (OR 0.86; 95% CI 0.61 to 1.2). CONCLUSIONS: The COVID-19 pandemic led to a decrease in the number of transplants. Patients with T1D have more rejection of the transplanted organ than patients with T2D. Fewer women with T2D undergo KT. The presence of T1D is a risk factor for IHM.

Hidatidosis pulmonar como causa de hemoptisis recidivante / Pulmonary hydatidosis as a cause of recurrent hemoptysis

La hidatidosis es una zoonosis poco frecuente causada por cestodos del género Echinococcus. El órgano afectado con mayor frecuencia es el hígado, seguido del pulmón. La hidatidosis pulmonar se caracteriza por cursar de forma asintomática en la mayoría de los casos, y en muchas ocasiones suele ser un hallazgo casual en estudios realizados con otros fines. El diagnóstico resulta complejo por la diversidad de la presentación clínica, las pruebas serológicas pueden resultar negativas y los hallazgos de laboratorio son inespecíficos, por lo que debería ser un diagnóstico a tener en cuenta sobre todo en zonas con alta prevalencia de esta infestación. (AU)

Hydatidosis is a rare zoonosis caused by cestodes of the genus Echinococcus. The most frequently affected organ is the liver, followed by the lung. Pulmonary hydatidosis is characterized by an asymptomatic course in most cases, and in many cases it is usually an incidental finding in studies performed for other purposes. The diagnosis is complex due to the diversity of the clinical presentation, serological tests can be negative and laboratory findings are nonspecific, so it should be a diagnosis to consider especially in areas with high prevalence of this infestation. (AU)

Enfermedad pulmonar obstructiva crónica y salud respiratoria / Chronic obstructive pulmonary disease and respiratory health

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad que cursa con manifestaciones multisistémicas y agudizaciones, y que conlleva una importante carga de morbilidad, mortalidad y costes sanitarios. Distintas medidas terapéuticas y de prevención juegan un papel importante en mejorar el pronóstico y la salud respiratoria de estos pacientes. Realizar actividad física de forma generalizada, llevar a cabo unos hábitos dietéticos y nutricionales adecuados, abandonar el consumo de tabaco y alcanzar un estado de inmunización óptimo son varias de las acciones de salud recomendadas. Estas también enlentecerán el proceso de envejecimiento. Además, se recomienda realizar políticas de salud pública para reducir la contaminación del aire y el cambio climático. Por último, debemos prestar especial atención a las características del sueño de estos pacientes y llevar a cabo un abordaje terapéutico que incluya una mejor calidad del sueño. (AU)

Chronic obstructive pulmonary disease (COPD) is a disease with multisystemic manifestations and exacerbations that lead to a significant burden of morbidity, mortality, and health care costs. Various therapeutic and preventive measures play an important role in improving the prognosis and respiratory health of the patients. General physical activity, proper dietary and nutritional habits, smoking cessation, and achieving an optimal immunization status are some of the recommended health actions. They also slow down the aging process. In addition, public health policies are recommended to reduce air pollution and climate change. Finally, we should pay special attention to the sleep characteristics of these patients and carry out a therapeutic approach that includes better sleep quality. (AU)

Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).

Practical Approaches to the Management of Cardiorenal Disease beyond Congestion.

BACKGROUND: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. SUMMARY: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. KEY MESSAGES: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.

Advances and Challenges in COVID-19 and Pneumonia.

In recent years, the pandemic caused by SARS-CoV-2 has posed a significant challenge to the entire medical community [...].

Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Multidisciplinary Management of Patients With Chronic Obstructive Pulmonary Disease and Cardiovascular Disease.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist, increasing the prevalence of both entities and impacting on symptoms and prognosis. CVD should be suspected in patients with COPD who have high/very high risk scores on validated scales, frequent exacerbations, precordial pain, disproportionate dyspnea, or palpitations. They should be referred to cardiology if they have palpitations of unknown cause or angina pain. COPD should be suspected in patients with CVD if they have recurrent bronchitis, cough and expectoration, or disproportionate dyspnea. They should be referred to a pulmonologist if they have rhonchi or wheezing, air trapping, emphysema, or signs of chronic bronchitis. Treatment of COPD in cardiovascular patients should include long-acting muscarinic receptor antagonists (LAMA) or long-acting beta-agonists (LABA) in low-risk or high-risk non-exacerbators, and LAMA/LABA/inhaled corticosteroids in exacerbators who are not controlled with bronchodilators. Cardioselective beta-blockers should be favored in patients with CVD, the long-term need for amiodarone should be assessed, and antiplatelet drugs should be maintained if indicated.