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Vaccination in patients with special medical situations remains a major challenge for health professionals. In recent years, vaccination of these groups has gained special importance because of the conceptual expansion of vaccines associated with early stages of life and the availability of specific vaccines for these patients (adjuvanted or high-burden). On the other hand, new scientific evidence on the definition of new immunopreventable risks is improving the indications and uses of vaccines. In addition, the use of new technologies, as well as indirect information sources for the identification of these patients, contribute significantly to the increase in vaccination coverage.

Resumen Introduccion y objetivos La insuficiencia tricuspidea (IT) grave es una valvulopatia prevalente con una alta tasa de mortalidad. La guia vigente no define umbrales especificos para considerar a los pacientes para cirugia o procedimientos percutaneos. Por lo tanto, se suele derivarlos para intervencion en una etapa tardia de la enfermedad. Este estudio tiene como objetivo evaluar los predictores de los eventos cardiovasculares en una cohorte prospectiva de pacientes con IT grave remitidos para cirugia. Metodos Se trata de un estudio observacional, prospectivo y no aleatorizado. Todos los pacientes se sometieron a cirugia por IT grave segun las guias clinicas vigentes. Se realizo anamnesis completa, analisis de sangre, ecocardiograma, resonancia magnetica cardiovascular y cateterismo derecho e izquierdo. Se siguio a los pacientes en la consulta externa y se registro un criterio de valoracion combinado (hospitalizacion por insuficiencia cardiaca o muerte de causa cardiovascular). Resultados Se incluyo a 43 pacientes consecutivos (edad, 66,9 ± 9,6 anos; el 67,4% mujeres). En todos los casos se realizo anuloplastia tricuspidea. Despues de una mediana de seguimiento de 38 meses, 12 pacientes (27,9%) presentaron el criterio combinado y 7 (16,3%) fallecieron. Por encima de todos los datos clinicos, sanguineos y de imagen, el volumen telediastolico del ventriculo derecho indexado constituyo el mejor predictor del objetivo combinado (HR = 1,1; p = 0,02) y de muerte de causa cardiovascular (HR = 1,1; p = 0,05). Ademas, el volumen telediastolico del ventriculo derecho indexado se asocio con la recurrencia de la IT despues de la cirugia, sin impacto en los resultados clinicos. Conclusiones En pacientes con IT grave remitidos para cirugia, el remodelado del ventriculo derecho evaluado por resonancia magnetica cardiovascular fue el mejor predictor independiente de desenlace cardiovascular en el seguimiento.

Recent epidemiological studies have shown that alcohol consumption can increase the risk of arterial hypertension, atrial fibrillation and gastrointestinal and breast cancer. Various sectors are therefore promoting abstinence from alcohol. However, light alcohol consumption has once again been shown to reduce the risk of myocardial infarction and diabetes but with an unclear effect on cerebrovascular disease. The decision to consume alcohol should therefore be an individual one based on personal factors. A level of consumption

Aims The implementation of the 2013 European Society of Cardiology (ESC) Core Curriculum guidelines for acute cardiovascular care (acc) training among European countries is unknown. We aimed to evaluate the current status of acc training among cardiology trainees and young cardiologists ( Methods and results The survey (March–July 2019) asked about details of cardiology training, self-confidence in acc technical and non-technical skills, access to training opportunities, and needs for further training in the field. Overall 614 young doctors, 31 (26–43) years old, 55% males were surveyed. Place and duration of acc training differed between countries and between centres in the same country. Although the majority of the respondents (91%) had completed their acc training, the average self-confidence to perform invasive procedures and to manage acc clinical scenarios was low—44% (27.3–70.4). The opportunities for simulation-based learning were scarce—18% (5.8–51.3), as it was previous leadership training (32%) and knowledge about key teamwork principles was poor (48%). The need for further acc training was high—81% (61.9–94.3). Male gender, higher level of training centres, professional qualifications of respondents, longer duration of acc/intensive care training, debriefings, and previous leadership training as well as knowledge about teamwork were related to higher self-confidence in all investigated aspects. Conclusions The current cardiology training program is burdened by deficits in acc technical/non-technical skills, substantial variability in programs across ESC countries, and a clear gender-related disparity in outcomes. The forthcoming ESC Core Curriculum for General Cardiology is expected to address these deficiencies.

Coronary artery disease (CAD) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. This process can be modified by lifestyle adjustments, pharmacological therapies, and invasive interventions designed to achieve disease stabilization or regression. The disease can have long, stable periods but can also become unstable at any time, typically due to an acute atherothrombotic event caused by plaque rupture or erosion. However, the disease is chronic, most often progressive, and hence serious, even in clinically apparently silent periods. The dynamic nature of the CAD process results in various clinical presentations, which can be conveniently categorized as either acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). The Guidelines presented here refer to the management of patients with CCS. The natural history of CCS is illustrated in Figure 1.

Inhibitors of proximal tubular Na+-glucose cotransporter 2 (SGLT2) are natriuretic, and they lower blood pressure. There are reports that the activities of SGLT2 and Na+-H+exchanger 3 (NHE3) are coordinated. If so, then part of the natriuretic response to an SGLT2 inhibitor is mediated by suppressing NHE3. To examine this further, we compared the effects of an SGLT2 inhibitor, empagliflozin, on urine composition and systolic blood pressure (SBP) in nondiabetic mice with tubule-specific NHE3 knockdown (NHE3-ko) and wild-type (WT) littermates. A single dose of empagliflozin, titrated to cause minimal glucosuria, increased urinary excretion of Na+and bicarbonate and raised urine pH in WT mice but not in NHE3-ko mice. Chronic empagliflozin treatment tended to lower SBP despite higher renal renin mRNA expression and lowered the ratio of SBP to renin mRNA, indicating volume loss. This effect of empagliflozin depended on tubular NHE3. In diabetic Akita mice, chronic empagliflozin enhanced phosphorylation of NHE3 (S552/S605), changes previously linked to lesser NHE3-mediated reabsorption. Chronic empagliflozin also increased expression of genes involved with renal gluconeogenesis, bicarbonate regeneration, and ammonium formation. While this could reflect compensatory responses to acidification of proximal tubular cells resulting from reduced NHE3 activity, these effects were at least in part independent of tubular NHE3 and potentially indicated metabolic adaptations to urinary glucose loss. Moreover, empagliflozin increased luminal α-ketoglutarate, which may serve to stimulate compensatory distal NaCl reabsorption, while cogenerated and excreted ammonium balances urine losses of this “potential bicarbonate.” The data implicate NHE3 as a determinant of the natriuretic effect of empagliflozin.

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients. The authors acknowledge the Heart Failure Association of the European Society of Cardiology for organizing the meeting during which this topic was discussed. The authors acknowledge T.J. for her expert review of the manuscript, and W.G. S., PharmD (Campbell University College of Pharmacy and Health Sciences), supported by the Heart Failure Association of the European Society of Cardiology for contributions to content development, writing, and editing the manuscript. J.M., C.M. and F.P. performed their expert review of the paper on behalf of Acute Cardiovascular Care Association of the European Society of Cardiology. J.B. and T.T. were supported by the Deutsche Forschungsgemeinschaft, Clinical Research Group 311 (KFO 311) '(Pre-)terminal heart and lung failure: unloading and repair' (DFG; TP1 and TP11). Harjola, VP (corresponding author), Helsinki Univ Hosp, Dept Emergency Med & Serv, Div Emergency Med, PL 340, Helsinki 00029, Finland. veli-pekka.harjola@hus.fi

Background Death and unexpected readmission are frequent among heart failure patients. We aimed to assess 30-day readmission and mortality rate as well as to identify predictive factors for patients discharged from a first HF related hospital admission. Methods and results Retrospective, single-center, cohort study, using administrative data from a tertiary care hospital in Barcelona, Spain. Patients discharged alive from a first HF related admission from 2010 to 2014 were assessed for 30-day death, readmission and adverse outcome rate. A Linear Logistic Regression Model was fitted for each outcome. The set accounted for 3642 patients; 50.1% female and 49.9% male. Mean age was 76 years (SD = 12). 30-Days rates were 9.2% for readmission, 5.6% for death and 13.8% for adverse outcome. Admission to an ED within 30 days was strongly linked to readmission (OR = 6.97), death (OR = 2.31) and adverse outcome (OR = 8.55), as well as chronic kidney disease (OR = 1.44/1.61/2.86 respectively). Discharge to a Long Stay Care (LSC) facility was linked to lower readmission and adverse event rates (OR = .57 and OR = .15). Conclusion Pre and post-index discharge use of health care resources is related to adverse outcome rates. Our findings point out the potential benefit for a more tailored approach in the management of HF patients.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient, MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD+) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.

Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we aimed at identifying the pathogenic processes underlying impaired adipocyte differentiation in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). We report that down-regulation of a key member of the major spliceosome, PRFP8/PRP8, as observed in IR/T2D preadipocytes from subcutaneous (SC) fat, prevented adipogenesis by altering both the expression and splicing patterns of adipogenic transcription factors and lipid droplet-related proteins, while adipocyte differentiation was restored upon recovery of PRFP8/PRP8 normal levels. Adipocyte differentiation was also compromised under conditions of endoplasmic reticulum (ER)-associated protein degradation (ERAD) hyperactivation, as occurs in SC and omental (OM) preadipocytes in IR/T2D obesity. Thus, targeting mRNA splicing and ER proteostasis in preadipocytes could improve adipose tissue function and thus contribute to metabolic health in obese individuals.

Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation–contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.

Adipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

The association between low bone mineral density (BMD) and inflammatory bowel disease (IBD) is already known. Our study, performed in Spanish pediatric IBD patients at diagnosis onset, shows that low BMD already existed at the beginning of the disease. Low weight and height are also associated with low BMD and have to be considered as risk factors. Introduction Inflammatory bowel disease (IBD) has been reported to be associated, even at disease onset, with low bone mass. The aim of this study was to know the bone mineral density (BMD) status in the IBD pediatric population of group of Spanish children, at the time of diagnosis. Material and methods Retrospective review of patients' records from pediatric IBD patients diagnosed in our unit in the last 10 years. BMD was measured at the time of diagnosis and was expressed by Z-score. Results Fifty-seven patients were included. Sixty-one percent were male and 47.4% had Crohn's disease (CD). Average age was 11.18 (SD 2.24) years old. Median BMD Z-score was - 0.30 (interquartile range: - 1.10 to + 0.10). Low BMD, defined as Z-score ≤ - 2SD, was present in 5% of patients, but there was no single patient with osteoporosis. There were no differences in BMD between Ulcerative Colitis (UC) and CD. Statistical differences appeared between healthy Spanish pediatric population and our IBD cohort, these having lower BMD for the same age and gender. A linear regression analysis showed a significant association between BMD Z-score and patient´s weight and height Z-score with a p values of 0.001 and 0.048, respectively. Conclusions Suboptimal bone density is present at diagnosis in Spanish pediatric patients with IBD. There is no difference in BMD between patients with CD and UC. Lower weight and height are associated with a lower BMD; thus these data at IBD diagnosis should be considered as a risk factor for bone disease in the pediatric population.

Cystic Fibrosis (CF) is a life-long genetic disease, causing increased energy needs and a healthy diet with a specific nutrient distribution. Nutritional status is an indicator of disease prognosis and survival. This study aimed at assessing the effectiveness of a self-management mobile app in supporting patients with CF to achieve the dietary goals set by the CF nutrition guidelines. A clinical trial was conducted in pancreatic insufficient children with CF, followed in six European CF centres, where the self-management app developed within the MyCyFAPP project was used for six months. To assess secondary outcomes, three-day food records were compiled in the app at baseline and after 3 and 6 months of use. Eighty-four subjects (mean 7.8 years old) were enrolled. Compared to baseline, macronutrient distribution better approximated the guidelines, with protein and lipid increasing by 1.0 and 2.1% of the total energy intake, respectively, by the end of the study. Consequently, carbohydrate intake of the total energy intake decreased significantly (-2.9%), along with simple carbohydrate intake (-2.4%). Regarding food groups, a decrease in ultra-processed foods was documented, with a concomitant increase in meat and dairy. The use of a self-management mobile app to self-monitor dietary intake could become a useful tool to achieve adherence to guideline recommendations, if validated during a longer period of time or against a control group. ispartof: NUTRIENTS vol:13 issue:6 ispartof: location:Switzerland status: published

Na+/H+exchanger isoform 3 (NHE3) contributes to Na+/bicarbonate reabsorption and ammonium secretion in early proximal tubules. To determine its role in the diabetic kidney, type 1 diabetic Akita mice with tubular NHE3 knockdown [Pax8-Cre; NHE3-knockout (KO) mice] were generated. NHE3-KO mice had higher urine pH, more bicarbonaturia, and compensating increases in renal mRNA expression for genes associated with generation of ammonium, bicarbonate, and glucose (phosphoenolpyruvate carboxykinase) in proximal tubules and H+and ammonia secretion and glycolysis in distal tubules. This left blood pH and bicarbonate unaffected in nondiabetic and diabetic NHE3-KO versus wild-type mice but was associated with renal upregulation of proinflammatory markers. Higher renal phosphoenolpyruvate carboxykinase expression in NHE3-KO mice was associated with lower Na+-glucose cotransporter (SGLT)2 and higher SGLT1 expression, indicating a downward tubular shift in Na+and glucose reabsorption. NHE3-KO was associated with lesser kidney weight and glomerular filtration rate (GFR) independent of diabetes and prevented diabetes-associated albuminuria. NHE3-KO, however, did not attenuate hyperglycemia or prevent diabetes from increasing kidney weight and GFR. Higher renal gluconeogenesis may explain similar hyperglycemia despite lower SGLT2 expression and higher glucosuria in diabetic NHE3-KO versus wild-type mice; stronger SGLT1 engagement could have affected kidney weight and GFR responses. Chronic kidney disease in humans is associated with reduced urinary excretion of metabolites of branched-chain amino acids and the tricarboxylic acid cycle, a pattern mimicked in diabetic wild-type mice. This pattern was reversed in nondiabetic NHE3-KO mice, possibly reflecting branched-chain amino acids use for ammoniagenesis and tricarboxylic acid cycle upregulation to support formation of ammonia, bicarbonate, and glucose in proximal tubule. NHE3-KO, however, did not prevent the diabetes-induced urinary downregulation in these metabolites.

Succinate is a signaling metabolite sensed extracellularly by succinate receptor 1 (SUNCR1). The accumulation of succinate in macrophages is known to activate a pro-inflammatory program; however, the contribution of SUCNR1 to macrophage phenotype and function has remained unclear. Here we found that activation of SUCNR1 had a critical role in the anti-inflammatory responses in macrophages. Myeloid-specific deficiency in SUCNR1 promoted a local pro-inflammatory phenotype, disrupted glucose homeostasis in mice fed a normal chow diet, exacerbated the metabolic consequences of diet-induced obesity and impaired adipose-tissue browning in response to cold exposure. Activation of SUCNR1 promoted an anti-inflammatory phenotype in macrophages and boosted the response of these cells to type 2 cytokines, including interleukin-4. Succinate decreased the expression of inflammatory markers in adipose tissue from lean human subjects but not that from obese subjects, who had lower expression of SUCNR1 in adipose-tissue-resident macrophages. Our findings highlight the importance of succinate-SUCNR1 signaling in determining macrophage polarization and assign a role to succinate in limiting inflammation., This study was supported by grants from the Spanish Ministry of Science, Innovation and Universities (PI14/00228 and PI17/01503 to J.V., SAF2015-65019-R to S.F.-V., SAF2014-56819-R and SAF2015-71878-REDT to A.C., BFU2016-78951-R to G.M.-M., PI15/00143 to C.S. and PI15/01562 to A.M., BFU2015-70454-REDT and BFU2017-90578-REDT to S.F.-V. and G.M.-M.) co-financed by the European Regional Development Fund (ERDF). The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) (CB07708/0012) is an initiative of the Instituto de Salud Carlos III. N.K. is recipient of a predoctoral fellowship from MINECO, Spain (FPI, BES-2016-077745). C.S. acknowledges support from the ‘Ramón y Cajal’ program from MINECO (RYC2013-13186) and S.F.-V. the Miguel Servet tenure-track program (CP10/00438 and CPII16/00008) from the Fondo de Investigación Sanitaria, co-financed by the ERDF.

Objectives We evaluated the patient profile and outcomes of first heart failure (HF) related hospital admission patients in the 2010–2014 period. Design Retrospective, single-center, cohort study. Setting We used administrative data from a tertiary care hospital (Hospital Universitari de Bellvitge, Barcelona, Spain). Participants All patients with primary diagnosis of HF registered at the hospital discharge database from 2010 to 2014 were included, ruling out that HF was present 10 years prior to the current episode. Intervention Primary care HF diagnosis status was assessed in order to distinguish new onset from no-new onset patients. Main measures Descriptive, bivariate and multivariate analysis were performed using age, previous primary care HF diagnosis and in-hospital death as grouping variables. Significant variables were fitted into a Linear logistic regression model for each outcome. Results We selected 3868 first HF-related admissions (56.8% of all HF episodes). In 1220 patients (31.7%) HF was diagnosed by their primary care physician. Main pattern was a woman (OR = 2.4), with higher prevalence of hypertension (OR = 1.7), atrial fibrillation (OR = 1.3), chronic kidney disease (OR = 1.6) and mortality rate (9.8%). In-hospital death rate was 5.8%, age over 85 (OR = 5.57), chronic kidney disease (OR = 1.44) and length of stay over 7 days (OR = 1.90) being the main contributors. Conclusions First HF related admissions account for 56.7% of all HF episodes. Roughly one third of patients were already diagnosed by the time of their first hospital admission. Elderly women were the most frequent, but not the only, group of patients. Age, hospital stay and chronic kidney disease were the main contributors for in-hospital death.

Aortic valve surgery in non-elderly patients represents a very challenging patient population. The younger the patient is at the point of aortic valve intervention, the longer their anticipated life expectancy will be, with longer exposure to valve-related complications and risk for re-operation. Although the latest international guidelines recommend aortic valve repair in patients with aortic valve insufficiency, what we see in the real world is that the vast majority of these aortic valves are replaced. However, current prosthetic valves has now been shown to lead to significant loss of life expectancy for non-elderly patients up to 50% for patients in their 40s undergoing mechanical aortic valve replacement. Bioprostheses carry an even worse long-term survival, with higher rates of re-intervention. The promise of trans-catheter valve-in-valve technology is accentuating the trend of bioprosthetic implantation in younger patients, without yet the appropriate evidence. In contrast, aortic valve repair has shown excellent outcomes in terms of quality of life, freedom from re-operation and freedom from major adverse valve-related events with similar life expectancy to general population as it is also found for the Ross procedure, the only available living valve substitute. We are at a time when the paradigm of aortic valve surgery needs to change for the better. To better serve our patients, we must acquire high quality real-world evidence from multiple centers globally - this is the vision of the AVIATOR registry and our common responsibility.

Background Medication adherence is a complex area of behaviour. Little is known about what influences chronic patients to take their medicines. This study has aimed to compare and contrast the health-related beliefs, experiences and types of behaviour typical among patients who have at least one chronic condition and are following a pharmacological treatment in accordance with their level of medication adherence. Methods A questionnaire-based cross-sectional study, consisting of socio-demographic data, the 4-item Morisky-Green scale and 37 statements about health beliefs, perceptions and experiences, was conducted at different levels of healthcare (primary and tertiary settings). Results A total of 577 questionnaires were analyzed. Respondents had a mean age of 64 and took an average of 4.6 drugs. Optimal adherence was reported by 58.6% of respondents. Bivariate analysis showed adherent subjects were older, took more medications, were in better spirits and had greater confidence and information regarding their treatment. Multivariate analysis found older age and the statements 'My doctor periodically reviews my treatment' and 'I am motivated to continue with the treatment' to be significantly related to medication adherence, while 'I make variations when taking medication depending on how I feel' was significant for medication non-adherence. Conclusion Medication non-adherence is common among chronic patients. Patient-centred approaches should be implemented in daily clinical practice as patient health beliefs, experiences and conduct influence medication-taking. Motivational interviewing might improve medication adherence in permitting emotional state managing and increasing educational skills, patient motivation and confidence between patients and healthcare providers.

The goal of an IVF cycle is the birth of at least one baby per intention to treat. However, IVF cannot confer competence on an embryo, but only can provide each couple with a safe treatment to meet a predetermined chance of success. This commentary highlights how clinical, financial and patient-centred perspectives should be included in the definition of success in IVF. The primary outcome, which is the cumulative live birth delivery rate per intention to treat, must always be complemented by analyses of risks, costs and time invested, as well as by measures of patient satisfaction. Finally, it is essential, whenever clinical conditions exist, to limit treatment discontinuation after failed attempts. Constant monitoring of the data is pivotal and must be adjusted for patient characteristics and compared with national and international registers. The authors aimed to review all these aspects and highlight the points that are still open for discussion. Is it time for a consensus?

Vigor reflects how motivated one is to respond to a stimulus. We previously showed that humans are more vigorous when more reward is available on average, and that this relationship is modulated by the dopamine precursor levodopa. Dopamine signalling and probabilistic reward learning degrade with age, so the relationship between vigor and reward should change with age. We test this and assess whether the relationship between vigor and reward correlates with D1 dopamine receptor availability measured using Positron Emission Tomography. We measured response times of 30 older and 30 younger subjects during an oddball discrimination task where rewards varied systematically between trial. Reward rate had a similar impact on the vigor of both groups. We observed a weak positive association across subjects between ventral striatal dopamine receptor availability and effect of average reward rate on response time, which was in the opposite direction to our prediction. Overall, the effect of reward on response vigor is similar between younger and older humans and is weakly sensitive to dopamine D1 receptor availability.

Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population. Thymic epithelial tumors (TETs) encompass a variety of histologic subtypes associated with different clinical outcomes. Due to its rarity in children, TETs' management requires a multidisciplinary approach. However, prognosis remains still poor, especially among patients with thymic carcinoma. This study presents the internationally recognized recommendations for the diagnosis and treatment of thymic tumors in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Paediatric Rare Tumours Network - European Registry (PARTNER).

INTRODUCTION: The objective of this study was to assess the diagnostic value of the "lever sign test" to diagnose ACL rupture and to compare this test to the two most commonly used, the Lachman and anterior drawer test. METHOD: This prospective study was performed in the ED of the Cliniques Universitaires Saint-Luc (Brussels, Belgium) from March 2017 to May 2019. 52 patients were included undergoing knee trauma, within 8 days, with an initial radiograph excluding a fracture (except Segond fracture or tibial spine fracture). On clinical investigation, patients showed a positive lever sign test and/or a positive Lachman test and/or a positive anterior drawer test. Exclusion criteria were a complete rupture of the knee extensor mechanism and patellar dislocation. All the physicians involved in this study were residents in training. An MRI was performed within 3 weeks for all included patients after the clinical examination. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were investigated for all three tests with MRI used as our reference standard. RESULTS: Forty out of 52 patients suffered an ACL rupture (77%) and 12 did not (23%). The sensitivity, specificity, PPV and NPV of the lever sign test were respectively 92.5%, 25% 82% and 50%. Those of the Lachman test were 54%, 54.5%, 81% and 25%, and those of the anterior drawer test were 56%, 82%, 90.5% and 37.5%. Twelve out of 40 ACL ruptures (30%) were diagnosed exclusively with a positive lever sign test. CONCLUSION: When investigating acute ACL ruptures (< 8 days) in the ED, the lever sign test offers a sensitivity of 92.5%, far superior to that of other well-known clinical tests. The lever sign test is relatively pain-free, easy to perform and its visual interpretation requires less experience. Positive lever sign test at the ED should lead to an MRI to combine high clinical sensitivity with high MRI specificity.

Preadipocytes are crucial for healthy adipose tissue expansion. Preadipocyte differentiation is altered in obese individuals, which has been proposed to contribute to obesity-associated metabolic disturbances. Here, we demonstrate that impaired alternative splicing and dysregulated endoplasmic reticulum (ER)- associated protein degradation (ERAD) represent marker pathways of dysfunctional preadipocytes in obese individuals with insulin resistance (IR)/type 2 diabetes (T2D). Down-regulation of a key member of the major spliceosome, PRFP8/PRP8, as observed in IR/T2D preadipocytes from subcutaneous (SC) fat, prevented adipogenesis by altering both the expression and splicing patterns of adipogenic transcription factors and lipid droplet-related proteins, while adipocyte differentiation was restored upon recovery of PRFP8/PRP8 normal levels. Adipocyte differentiation was also compromised under conditions of ERAD hyperactivation, as occurs in SC and omental (OM) preadipocytes in IR/T2D obesity. Thus, targeting mRNA splicing and ER proteostasis in preadipocytes could improve adipose tissue function and thus contribute to metabolic health in obese individuals.

Altres ajuts: Ministerio de Sanidad; Fondo Europeo de Desarrollo Regional (FEDER); Fundació La Marató de TV3 (2015/2510). Background and objective: Although recommended for the treatment of acute heart failure (AHF), the use of intravenous (IV) nitroglycerin (NTG) is supported by scarce and contradicting evidence. In the current analysis, we have assessed the impact of IV NTG administration by EMS or in emergency department (ED) on outcomes of AHF patients. Methods: We analyze AHF patients included by 45 hospitals that were delivered to ED by EMS. Patients were grouped according to whether treatment with IV NTG was started by EMS before ED admission (preED-NTG), during the ED stay (ED-NTG) or were untreated with IV NTG (no-NTG, control group). In-hospital, 30-day and 365-day all-cause mortality, prolonged hospitalization (>7 days) and 90-day post-discharge combined adverse events (ED revisit, hospitalization or death) were compared in EMS-NTG and ED-NTG respect to control group. Results: We included 8424 patients: preED-NTG = 292 (3.5%), ED-NTG = 1159 (13.8%) and no-NTG = 6973 (82.7%). preED-NTG group had the most severely decompensated cases of AHF (p < 0.001) but it had lower in-hospital (OR = 0.724, 95%CI = 0.459-1.114), 30-day (HR = 0.818, 0.576-1.163) and 365-day mortality (HR = 0.692, 0.551-0.869) and 90-day post-discharge events (HR = 0.795, 0.643-0.984) than control group. ED-NTG group had mortalities similar to control group (in-hospital: OR = 1.164, 0.936-1.448; 30-day: HR = 0.980, 0.819-1.174; 365-day: HR = 0.929, 0.830-1.039) but significantly decreased 90-day post-discharge events (HR = 0.870, 0.780-0.970). Prolonged hospitalization rate did not differ among groups. Five different analyses confirmed these findings. Conclusions: Early prehospital IV NTG administration was associated with lower mortality and post-discharge events, while IV NTG initiated in ED only improved post-discharge event rate. Further studies are needed to assess the role of early prehospital administration of IV NTG to patients with AHF.

Resumen Antecedentes y objetivos Evaluar si los sintomas/signos de congestion en pacientes con insuficiencia cardiaca aguda (ICA) atendidos en los servicios de urgencias hospitalarios (SUH) permiten predecir la evolucion a corto plazo. Pacientes y metodos Pacientes consecutivos diagnosticados de ICA en 45 SUH del registro EAHFE. Recogimos variables clinicas de congestion sistemica (edemas en miembros inferiores, ingurgitacion yugular, hepatomegalia) y pulmonar (disnea de esfuerzo, disnea paroxistica nocturna, ortopnea y crepitantes pulmonares) analizando su asociacion con la mortalidad por cualquier causa a 30 dias, de forma cruda y ajustada por diferencias entre grupos. Resultados Analizamos 18.120 pacientes (mediana = 83 anos, rango intercuartil [RIC] = 76-88; mujeres = 55,7%). El 44,6% presentaba > 3 sintomas/signos congestivos. Individualmente, el riesgo ajustado de muerte a 30 dias se incremento un 14% para la existencia de ingurgitacion yugular (hazard ratio [HR] = 1,14; intervalo de confianza al 95% [IC 95%] = 1,01-1,28) y un 96% para la disnea de esfuerzo (HR = 1,96; IC 95% = 1,55-2,49). Valorados conjuntamente, el riesgo se incremento progresivamente con el numero de sintomas/signos presentes; asi, respecto a los pacientes sin sintomas/signos de congestion, el riesgo incremento un 109, 123 y 156% en pacientes con 1-2, 3-5 y 6-7 sintomas/signos, respectivamente. Estas asociaciones no mostraron interaccion con la disposicion final del paciente tras su atencion en urgencias (alta/hospitalizacion), con excepcion de edemas en extremidades inferiores, que tuvieron mejor pronostico en pacientes dados de alta (HR = 0,66; IC 95% = 0,49-0,89) que en los hospitalizados (HR = 1,01; IC 95% = 0,65-1,57; p interaccion Conclusion La presencia de mayor numero de sintomas/signos congestivos se asocio a una mayor mortalidad de cualquier causa a los 30 dias. Individualmente, la ingurgitacion yugular y la disnea de esfuerzo se asocian a mayor mortalidad a corto plazo.

Background Prescription opioids usage is on the rise. There has been an increasing recognition that chronic opioid consumption can result in esophageal motility disorders and this association has been named opioid-induced esophageal dysfunction (OIED). Aims Analyze the prevalence of chronic opioid consumption in patients referred for esophageal motility testing in a European center and to describe the clinical characteristics and the association of opioid consumption in esophageal motility disorders. METHODS Retrospective descriptive study in patients who had HRM performed in a single center. The clinical history in the electronic medical reports was reviewed. RESULTS The prevalence of opioid prescription in patients referred to our institution was 10.1% and 4.8% patients were on active chronic opioid use. We found a 32% prevalence of OIED. Comparing chronic active opioid user (CAOU) patients with OIED and CAOU patients without OIED, there was a higher prevalence of male sex (43.8% vs 8.8% p value=0.007). Converting the different opioids medication to morphine milligram equivalent daily dose (MMED), CAOU patients with OIED had a higher MMED than CAOU patients without OIED (125.2±31.3 vs 33.4±5.7 MME p=0.041). Dysphagia was the most common indication for performing an HRM in 60.0% in CAOU patients. Furthermore, dysphagia was more frequent in CAOU patients with OIED (87.5% vs 47.0% p= 0.019). CONCLUSIONS Patients on chronic opioids with OIED complained mostly dysphagia. We found an association of male sex and a higher dose of opioids in CAOU patients with esophageal motility disorders.

The study reports a case of a 57-year-old female patient with incidental right adrenal lipoma (LA). The tumor was detected by ultrasound (US) and confirmed by computed tomography (CT). Due to the size of the mass, it was decided to perform a laparoscopic adrenalectomy. During the differential microscopic diagnosis, were considered adrenal lipomatous tumors, myelolipoma, angiomyolipoma and teratomas, among others. In all these neoplasms, LA is a rare tumor, with only 24 cases reported in the anglo-saxon literature revised. It is a benign adrenal gland tumor with generally asymptomatic and non-functioning nature.

Aims The effect of early administration of intravenous (IV) furosemide in the emergency department (ED) on short-term outcomes of acute heart failure (AHF) patients remains controversial, with one recent Japanese study reporting a decrease of in-hospital mortality and one Korean study reporting a lack of clinical benefit. Both studies excluded patients receiving prehospital IV furosemide and only included patients requiring hospitalization. To assess the impact on short-term outcomes of early IV furosemide administration by emergency medical services (EMS) before patient arrival to the ED. Methods and results In a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency Departments (EAHFE) registry of consecutive AHF patients admitted to Spanish EDs, patients treated with IV furosemide at the ED were classified according to whether they received IV furosemide from the EMS (FAST-FURO group) or not (CONTROL group). In-hospital all-cause mortality, 30-day all-cause mortality, and prolonged hospitalization (>10 days) were assessed. We included 12 595 patients (FAST-FURO = 683; CONTROL = 11 912): 968 died during index hospitalization [7.7%; FAST-FURO = 10.3% vs. CONTROL = 7.5%; odds ratio (OR) = 1.403, 95% confidence interval (95% CI) = 1.085–1.813; P = 0.009], 1269 died during the first 30 days (10.2%; FAST-FURO = 13.4% vs. CONTROL = 9.9%; OR = 1.403, 95% CI = 1.146–1.764; P = 0.004), and 2844 had prolonged hospitalization (22.8%; FAST-FURO = 25.8% vs. CONTROL = 22.6%; OR = 1.189, 95% CI = 0.995–1.419; P = 0.056). FAST-FURO group patients had more diabetes mellitus, ischaemic cardiomyopathy, peripheral artery disease, left ventricular systolic dysfunction, and severe decompensations, and had a better New York Heart Association class and had less atrial fibrillation. After adjusting for these significant differences, early IV furosemide resulted in no impact on short-term outcomes: OR = 1.080 (95% CI = 0.817–1.427) for in-hospital mortality, OR = 1.086 (95% CI = 0.845–1.396) for 30-day mortality, and OR = 1.095 (95% CI = 0.915–1.312) for prolonged hospitalization. Several sensitivity analyses, including analysis of 599 pairs of patients matched by propensity score, showed consistent findings. Conclusion Early IV furosemide during the prehospital phase was administered to the sickest patients, was not associated with changes in short-term mortality or length of hospitalization after adjustment for several confounders.

Background Abnormal lipid metabolism is observed in gestational diabetes mellitus (GDM) and in neonates with abnormal fetal growth, however, how these alterations specifically affect the umbilical cord blood lipoprotein profile is not well understood. Objective To assess the impact of GDM on the cord blood lipoprotein profile across birth-weight categories by using Advanced Lipoprotein Testing. Methods observational study involving 74 control and 62 GDM pregnant women and their offspring. Newborns were classified according to birth-weight as small (n = 39), adequate (n = 50) or large (n = 49) for gestational age (SGA, AGA and LGA, respectively). Two-dimensional diffusion-ordered 1H-NMR spectroscopy was used to profile umbilical cord serum lipoproteins. One hundred and three children were available in a two years follow-up study to evaluate associations between cord blood lipid profile and obesity. Results Baseline characteristics of the two groups were similar except for gestational weight gain. The size, lipid content, number and concentration of particles within their subclasses were similar between offspring born to GDM and control mothers. Using two-way analysis of variance, we observed an interaction between GDM and birth-weight categories for IDL-cholesterol content and IDL- and LDL-triglyceride content, and the number of medium VLDL and LDL particles, specifically in AGA neonates. Small LDL particles were independently associated with offspring obesity at two years. Conclusions In this selected cohort, GDM disturbs triglyceride and cholesterol lipoprotein content across birth-weight categories, and AGA neonates born to GDM mothers display a profile more similar to adults with dyslipidemia and atherosclerosis than to those born to mothers with normal glucose tolerance.

In-hospital mortality following Type A acute aortic dissection (TAAAD) repair was 23.9% in a 2007 International Registry of Acute Aortic Dissection (IRAD) report. Recent publications have described surgical mortality as low as 12.2%. This study evaluates the fitness of a previously published risk

Background Hyperoxia produces reactive oxygen species, apoptosis, and vasoconstriction, and is associated with adverse outcomes in patients with heart failure and cardiac arrest. Our aim was to evaluate the association between hyperoxia and mortality in patients (pts) receiving positive pressure ventilation (PPV) in the cardiac intensive care unit (CICU). Methods Patients admitted to our medical center CICU who received any PPV (invasive or non-invasive) from 2001 through 2012 were included. Hyperoxia was defined as time-weighted mean of PaO2 >120mmHg and non-hyperoxia as PaO2 ≤120mmHg during CICU admission. Primary outcome was in-hospital mortality. Multivariable logistic regression was used to assess the association between hyperoxia and in-hospital mortality adjusted for age, female sex, Oxford Acute Severity of Illness Score, creatinine, lactate, pH, PaO2/FiO2 ratio, PCO2, PEEP, and estimated time spent on PEEP. Results Among 1493 patients, hyperoxia (median PaO2 147mmHg) during the CICU admission was observed in 702 (47.0%) pts. In-hospital mortality was 29.7% in the non-hyperoxia group and 33.9% in the hyperoxia group ((log rank test, p=0.0282, see figure). Using multivariable logistic regression, hyperoxia was independently associated with in-hospital mortality (OR 1.507, 95% CI 1.311–2.001, p=0.00508). Post-hoc analysis with PaO2 as a continuous variable was consistent with the primary analysis (OR 1.053 per 10mmHg increase in PaO2, 95% CI 1.024–1.082, p=0.0002). Conclusions In a large CICU cohort, hyperoxia was associated with increased mortality. Trials of titration of supplemental oxygen across the full spectrum of critically ill cardiac patients are warranted. Funding Acknowledgement Type of funding source: None

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc., Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate–dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Background and Aims Atherosclerosis and its related clinical complications are the leading causes of death in western countries. Multiple processes are involved in atherosclerosis like endothelial dysfunction, inflammation, vascular proliferation, neovascularization, oxidative stress, apoptosis, extracellular matrix degradation and thrombosis. Moreover atherosclerosis could be accelerated in some diseases like chronic kidney disease (CKD). In this regard, miRNAs have been elucidated as important factors in the regulation of different cellular and molecular processes involved in atherosclerosis development. Our aim is to identify specific miRNAs that could be involved in chronic kidney disease (CKD) accelerated-atherosclerosis. Method A CKD accelerated-atherosclerosis mouse model was developed by subtotal nephrectomy (5/6 nephrectomy) in APOE-/- mice fed on a high fat diet (HFD) during 10 weeks and compared to mice with normal renal function. Urine and blood samples were collected every week. Western-blot, RT-PCR, immunohistochemistry and confocal microscopy analysis were performed. In previous studies mir23a-3p and miR652-3p have been suggested as possible regulators of the atherosclerotic process. Therefore the expression levels of these miRNAs and its possible target genes (FER and BTLA) were analyzed in mice total blood. Results APOE-/-+ERC+HFD mouse showed a progressive decrease in renal function and an increase of renal damage markers such as KIM-1. These animals showed structural glomerular damage characterized by de-cellularization, mesangial cell expansion and podocyte (WT1+,podocalixin+), endothelial (CD31+) and mesangial (GATA3+) loss. Lipid profile modifications were also observed in APOE-/-+ERC+HFD mice with an increase in plasma total cholesterol levels. Moreover atherosclerotic plaque size was also increased in APOE-/-+ERC+HFD animals in comparison with atherosclerotic plaque size of APOE-/-+HFD mice. CKD mice showed lower fibrosis (sirius red staining) and higher inflammatory markers in its atherosclerotic plaques. The presence of macrophages (CD68+) and T lymphocytes (CD3+) was increased in APOE-/-+ERC+HFD group in contrast with APOE-/-+HFD animals. Moreover, in samples from the aortic arch of APOE-/-+ERC+HFD mice, ICAM1 protein levels were increased. Finally we found decreased levels of mir23a-3p and mir652-3p gene in total blood samples of APOE-/-+ ERC+ HFD mice. On the other hand, in aortic arc and descendent aorta tissues, mir23a-3p and mir652-3p expression levels were similar between groups. The expression levels of mRNAs of potential targets of this miRNAs (FER and BTLA) were increased in total blood and aortic arch samples. In addition, we observed that BTLA and FER expression were localized in vascular smooth muscle cells and endothelial cells respectively. Conclusion Levels of mir23a-3p, mir652-3p and its related mRNA (FER and BTLA) are altered in CKD and may be a potential therapeutic target for CKD-accelerated atherosclerosis treatment.

Atrial fibrillation and acute heart failure frequently co-exist and can exacerbate each other. Their combination leads to increased morbidity and mortality. However, the prevalence and significance, as well as the treatment, of atrial fibrillation in acute heart failure are not well studied. Management of atrial fibrillation in acute heart failure requires a multidisciplinary team approach. Treatment of underlying disease(s), identification and treatment of potentially correctable causes and precipitating factors and anticoagulation are crucial. In this article, current evidence on atrial fibrillation in the setting of acute heart failure is summarised. The recommendations on management of atrial fibrillation in the prehospital stage, the treatment of reversible causes, when and how to use rate or rhythm control, maintenance of sinus rhythm, catheter ablation and pacing, anticoagulation, as well as measures on prevention of atrial fibrillation are provided.

Acute heart failure (AHF) continues to be a substantial cause of illness and death, with in-hospital and 3-month mortality rates of 5% and 10%, respectively, and 6-month re-admission rates in excess of 50% in a range of clinical trials and registry studies; the European Society of Cardiology (ESC) Heart Failure Long-Term Registry recorded a 1-year death or rehospitalization rate of 36%. As regards the short-term treatment of AHF patients, evidence was collected in the ESC Heart Failure Long-Term Registry that intravenous (i.v.) treatments are administered heterogeneously in the critical phase, with limited reference to guideline recommendations. Moreover, recent decades have been characterized by a prolonged lack of successful innovation in this field, with a plethora of clinical trials generating neutral or inconclusive findings on long-term mortality effects from a multiplicity of short-term interventions in AHF. One of the few exceptions has been the calcium sensitizer and inodilator levosimendan, introduced 20 years ago for the treatment of acutely decompensated chronic heart failure. In the present review, we will focus on the utility of this agent in the wider context of i.v. inotropic and inodilating therapies for AHF and related pathologies.

Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets., “La Caixa” Banking Foundation under project codes HR18-00068 (to M.R.C. and J.M.R.) and HR17-00247 (to J.V.); Spanish Ministerio de Ciencia e Innovación grants RTI2018-099246-B-I00 (MICIU/AEI/FEDER, UE) and SAF2015-636333R (MINECO/FEDER, UE) to J.M.R., SAF2017-88881R (MINECO/AEI/FEDER, UE) to M.R.C., and BIO2015-67580-P and PGC2018-097019-B-I00 to J.V.; the Comunidad de Madrid

To evaluate the safety profile and the number of usable blastocysts on day 5 and on day 6 after treatment with an individualized dosing regimen of a follitropin delta and highly purified human menopausal gonadotropin (HP-hMG) for controlled ovarian stimulation.Multicenter, open label, exploratory study.Reproductive medicine clinics.A total of 110 patients (aged 18-40 years).Follitropin delta coadministered with HP-hMG, with follitropin delta dose fixed according to an established algorithm and HP-hMG dose at 75 IU when the follitropin delta starting dosage was12 μg; 150 IU when follitropin delta dosage was 12 μg and weight100 kg, and 225 IU when follitropin delta dosage was 12 μg and weight ≥100 kg (dosage adjustments confined to HP-hMG only).Mean number of good-quality blastocysts obtained at day 5 and day 6 as well as the proportion of women with ovarian hyperstimulation syndrome (OHSS).A cohort study was compared with the follitropin delta group from the Evidence-based Stimulation Trial with Human Recombinant Follicle-Stimulating Hormone in Europe and Rest of World 1 (ESTHER-1) study. Even when stratified by age, a statistically significantly higher mean in the number of oocytes retrieved and number of good-quality blastocysts was observed in this study compared with the ESTHER-1 trial in which follitropin delta was used alone. The rate of patients triggered with a gonadotropin-releasing hormone agonist was statistically significantly higher in our Menopur and Rekovelle Combined Study (MARCS) cohort (43%) when compared with the rates reported in the follitropin delta cohort in the ESTHER-1 study (2.3%). Incidence of any grade of OHSS was 9.3% in the present study compared to 2.6% in follitropin delta group from ESTHER-1 trial. No cases of moderate or severe OHSS were observed in our study compared with 1.4% in the follitropin delta group of ESTHER-1.Optimizing the ovarian response during in vitro fertilization employing a mixed protocol of individualized dosing of follitropin delta and HP-hMG resulted in a statistically significant number of usable blastocysts on days 5 and 6 with an increased risk of mild OHSS, which did not require medical intervention or hospitalization.NCT03483545.

Introduction and objectives: To determine whether structural/organizational characteristics of hospitals and emergency departments (EDs) affect acute heart failure (AHF) outcomes. Methods: We performed a secondary analysis of the EAHFE Registry. Six hospital/ED characteristics were collected and were related to 7 postindex events and postdischarge outcomes, adjusted by the period of patient inclusion, baseline patient characteristics, AHF episode features, and hospital and ED characteristics. The relationship between discharge directly from the ED (DDED) and outcomes was assessed, and interaction was analyzed according to the hospital/ED characteristics. Results: We analyzed 17 974 AHF episodes included by 40 Spanish EDs. Prolonged stays were less frequent in high-technology hospitals and those with hospitalization at home and with high-inflow EDs, and were more frequent in hospitals with a heart failure unit (HFU) and an ED observation unit. In-hospital mortality was lower in high-technology hospitals (OR, 0.78; 95%CI, 0.65-0.94). Analysis of 30-day postdischarge outcomes showed that hospitals with a short-stay unit (SSU) had higher hospitalization rates (OR, 1.19; 95%CI, 1.02-1.38), high-inflow EDs had lower mortality (OR, 0.73; 95%CI, 0.56-0.96) and fewer combined events (OR, 0.87; 95%CI, 0.76-0.99), while hospitals with HFU had fewer ED reconsultations (OR, 0.83; 95%CI, 0.76-0.91), hospitalizations (OR, 0.85; 95%CI, 0.75-0.97), and combined events (OR, 0.84; 95%CI, 0.77-0.92). The higher the percentage of DDED, the fewer the prolonged stays. Among other interactions, we found that more frequent DDED was associated with more 30-day postdischarge reconsultations, hospitalizations and combined events in hospitals without SSUs, but not in hospitals with an SSU. Conclusions: AHF outcomes were significantly affected by the structural/organizational characteristics of hospitals and EDs and their aggressiveness in ED management. (C) 2020 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

In celiac disease (CD) there is a need for precise and non-invasive tools to assess dietary compliance to the gluten-free diet (GFD). Our aim is to evaluate the efficacy of the detection of gluten immunogenic peptides (GIP) in feces, to monitor in real life, the adherence to GFD in pediatric patients with CD. A cross-sectional, prospective study was conducted. Fecal samples from CD children were analyzed by a rapid immunochromatographic (IC) test and by an ELISA method, both based on the antigliadin 33-mer monoclonal antibody. Group 1 comprises 43 children on a GFD. According to the food records (FR), 39/43 patients were compliant with the GFD and gluten consumption was recorded in 4. GIP were detected in 15/43 individuals by the ELISA method and also in 7 by IC strips. Group 2: comprise 18 children at CD diagnosis; GIP levels decreased over time (p

INTRODUCTION AND OBJECTIVE:Immediate postoperative instillation (IPOP) of mitomycin-C (MMC) having been shown to be effective in preventing recurrence. 30% of patients are not suitable candidates f...

Introduction and objectives Severe tricuspid regurgitation (TR) is a prevalent valve disease with a high mortality rate. Current guidelines do not define specific thresholds at which patients should be considered for surgery or percutaneous procedures. Thus, patients are usually referred for intervention at a late stage of the disease. This study aimed to assess predictors of cardiovascular outcomes in a prospective cohort of patients with severe TR referred for surgery. Methods This was an observational, prospective, nonrandomized study. All patients underwent surgery for severe TR based on current clinical guidelines. Complete anamnesis, blood test, echocardiogram, cardiovascular magnetic resonance and right and left catheterization were performed. Patients were followed up in the outpatient department and a combined endpoint (hospitalization for heart failure and cardiovascular mortality) was registered. Results Forty-three consecutive patients were included (age: 66.9 ± 9.6 years, 67.4% female). Tricuspid annuloplasty was performed in all patients. After a median follow-up of 38 months, 12 patients (27.9%) showed the combined endpoint and 7 (16.3%) died. Above all clinical, blood and imaging data, the indexed right ventricular end-diastolic volume constituted the best predictor of the combined endpoint (HR, 1.1; P = .02) and cardiovascular mortality (HR, 1.1; P = .05). Furthermore, indexed right ventricular end-diastolic volume was associated with TR recurrence after surgery, with no impact on clinical outcomes. Conclusions In patients with severe TR referred for surgery, right ventricular remodeling assessed by cardiovascular magnetic resonance constituted the best independent predictor of cardiovascular outcomes at follow-up.

The latest acute heart failure (AHF) consensus document from the Spanish Society of Cardiology (SEC, for its initials in Spanish), Spanish Society of Internal Medicine (SEMI), and Spanish Society of Emergency Medicine (SEMES) was published in 2015, which made an update covering the main novelties regarding AHF from the last few years necessary. These include publication of updated European guidelines on HF in 2016, new studies on the pharmacological treatment of patients during hospitalization, and other recent developments regarding AHF such as early treatment, intermittent treatment, advanced HF, and refractory congestion. This consensus document was drafted with the aim of updating all aspects related to AHF and to create a document that comprehensively describes the diagnosis, treatment, and management of this disease. (C) 2020 Elsevier Espana, S.L.U. and Sociedad Espanola de Medicina Interna (SEMI). All rights reserved.

The previous ESC/EAS lipid Guidelines were published in August 2016. The emergence of a substantial body of evidence over the last few years has required new, up-to-date Guidelines. New evidence has confirmed that the key initiating event in atherogenesis is the retention of low- density lipoprotein (LDL) cholesterol (LDL-C) and other cholesterol-rich apolipoprotein (Apo) B containing lipoproteins within the arterial wall. Several recent placebo-controlled clinical studies have shown that the addition of either ezetimibe or anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) to statin therapy provides a further reduction in atherosclerotic cardiovascular disease (ASCVD) risk, which is directly and positively correlated with the incrementally achieved absolute LDL-C reduction. Furthermore, these clinical trials have clearly indicated that the lower the achieved LDL-C values, the lower the risk of future cardiovascular (CV) events, with no lower limit for LDL-C values, or ‘J’-curve effect.

Aims This study aimed to systematically identify and summarise all risk scores evaluated in the emergency department setting to stratify acute heart failure patients. Methods and results A systematic review of PubMed and Web of Science was conducted including all multicentre studies reporting the use of risk predictive models in emergency department acute heart failure patients. Exclusion criteria were: (a) non-original articles; (b) prognostic models without predictive purposes; and (c) risk models without consecutive patient inclusion or exclusively tested in patients admitted to a hospital ward. We identified 28 studies reporting findings on 19 scores: 13 were originally derived in the emergency department (eight exclusively using acute heart failure patients), and six in emergency department and hospitalised patients. The outcome most frequently predicted was 30-day mortality. The performance of the scores tended to be higher for outcomes occurring closer to the index acute heart failure event. The eight scores developed using acute heart failure patients only in the emergency department contained between 4–13 predictors (age, oxygen saturation and creatinine/urea included in six scores). Five scores (Emergency Heart Failure Mortality Risk Grade, Emergency Heart Failure Mortality Risk Grade 30 Day mortality ST depression, Epidemiology of Acute Heart Failure in Emergency department 3 Day, Acute Heart Failure Risk Score, and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) have been externally validated in the same country, and two (Emergency Heart Failure Mortality Risk Grade and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) further internationally validated. The c-statistic for Emergency Heart Failure Mortality Risk Grade to predict seven-day mortality was between 0.74–0.81 and for Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure to predict 30-day mortality was 0.80–0.84. Conclusions There are several scales for risk stratification of emergency department acute heart failure patients. Two of them are accurate, have been adequately validated and may be useful in clinical decision-making in the emergency department i.e. about whether to admit or discharge.