Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM-study programme

Aims We investigated the association between worsening renal function (WRF) that occurs during renin–angiotensin–aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fraction (HFREF). Methods and results We examined changes in estimated glomerular filtration rate (GFR) and the relationship between WRF (defined as ≥26.5 µmol/L and ≥25% increase in serum creatinine from baseline to 6 weeks) and outcome, according to randomized treatment, in patients with HFREF (EF <45%; n = 1569) and HFPEF (EF ≥45%; n = 836) in the CHARM programme. The primary outcome was cardiovascular death or HF hospitalization. Estimated GFR decreased 9.0 ± 21 vs. 4.0 ± 21 mL/min/1.73 m2 with candesartan and placebo, respectively, and this was similar in HFREF and HFPEF. WRF developed more frequently with candesartan, 16% vs. 7%, P < 0.001, with similar findings in patients with HFREF and HFPEF. WRF was associated with a higher risk of the primary outcome: multivariable hazard ratio (HR) 1.26, 95% confidence interval 1.03–1.54, P = 0.022, in both treatment groups, and in both HFREF and HFPEF (P for interaction 0.98). In HFREF, WRF was mostly related to HF hospitalization, while in HFPEF, WRF seemed more associated with mortality. Conclusions GFR decreased more and WRF was more common with candesartan compared with placebo, and this was similar in HFREF and HFPEF. WRF was associated with worse outcomes in HFREF and HFPEF. Although no formal interaction was present, the association between candesartan treatment, WRF, and type of clinical outcome was slightly different between HFREF and HFPEF

Greenrelisient: Agroecological approch to organic greenhouse production in Europe

All over Europe, organic greenhouse production systems are usually very intensive, which threatens their sustainability and the consumer trust. The implementation of less intensive production systems based on low energy consumption, appropriate crop rotations, use of agroecological service crops, and local organic inputs is possible at almost any latitude in Europe

EFFECTS OF COVER CROP MANAGEMENT AND COMPOST APPLICATION ON SOIL FERTILITY OF ORGANIC MELON

A field experiment was carried out in Central Italy on growing melon (Cucumis melo L.) after barley (Hordeum vulgare L.). Three different systems of cover crop termination (green manure, roller crimper and fallow, as control) were combined with three doses of compost (0, 15 and 30 t ha-1 d.m.) in a strip plot design. The main objective of the research was to evaluate their effects on organic melon production and on short and long term soil nitrogen (N) fertility. Marketable yield and quality and soil N availability along the melon cycle were determined and a simplified N budget calculated. Green manure (GM) treatment showed the highest total and marketable yield, followed by fallow (FA), while roller crimper (RC) was characterized by a significant lower yield respect to the other two treatments (45% and 62% of the marketable yield of GM and FA, respectively). On the other side, long term soil N fertility of GM and FA were characterized by N deficit unless combined with compost application at the dose of 15 t ha-1 d.m

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure

AimsRecent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF).Methods and resultsWe analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four-level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all-cause mortality. At a median follow-up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01–1.50], but this association was not homogeneous across CA125–BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51–3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73–2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55–0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36–2.76).ConclusionThe risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF

Investigating Physiological Determinants of Mental Health in Children with Cerebral Palsy

Background Fifty-seven percent of children with cerebral palsy (CP) experience mental health symptoms including symptoms of anxiety and depression. Although CP is non progressive, secondary conditions can have progressive effects on an individuals’ functional abilities. Particularly, untreated mental health symptoms can negatively affect a child’s quality of life. Children with CP also experience fatigue, pain, poor physical activity, and sleep disturbances. The presence of these physiological symptoms, separate and in combination, may impact mental health; however, it has not been systematically examined. Identifying factors that contribute to mental health symptoms may prevent the maintenance of these issues into adulthood. Objectives This study aimed to understand the associations between fatigue, pain, sleep, physical activity and mental health symptoms for children with CP. We hypothesized that moderate levels of fatigue, pain and/or sleep difficulties were associated with presence of psychological symptoms. In addition, we hypothesized that lower levels of physical activity were associated with mental health symptoms. Methods An observational study was conducted to assess physiological and mental health symptoms and physical activity in children with CP. Twenty-six participants and their caregivers responded to risk factor specific questionnaires before wearing accelerometers for one week, providing non-invasive data on movement patterns and sleep cycles. Using pairwise correlations and backward stepwise linear regressions, we examined the associations between the risk factors and severity of mental health symptoms. Results Significant regression models demonstrated associations for behavioural, depressive and anxiety related symptoms in children with CP. Models were able to explain 61%, 18% and 41% of the variance in child report internalizing behaviours, caregiver reported depression and anxiety, respectively. Conclusion Fatigue, pain severity, sleep efficiency and physical activity outcomes all contributed in some way to mental health outcomes. Longitudinal research is required to determine causal relationships. Future Applications This study will help develop evidence-based interventions to treat these factors and have the potential to inform clinicians on the determinants of mental health outcomes in this population. Individualized, targeted interventions can be developed and implemented to address the modifiable risk factors that threaten the wellbeing of children with CP

Blood urea nitrogen to creatinine ratio is associated with congestion and mortality in heart failure patients with renal dysfunction

Renal dysfunction (RD) and venous congestion are related and common in heart failure (HF). Studies suggest that venous congestion may be the primary driver of RD in HF. In this study, we sought to investigate retrospectively the relationship between common measures of renal function with caval congestion and mortality among outpatients with HF and RD. We reviewed data from 103 HF outpatients (45 males, mean age 74 years, ejection fraction 41.8 ± 11.6 %) with estimated glomerular filtration rate (eGFR) of 25.5 (adjusted OR 2.98, p 0.015) and eGFR ≤45.8 (adjusted OR 5.38, p 0.002) identify patients at risk for caval congestion; a BUN/Cr >23.7 was the best predictor of impaired collapsibility (adjusted OR 4.41, p 0.001). a BUN/Cr >25.5 (HR 2.19, 95 % CI 1.21-3.94, p < 0.001) and NYHA class 3 (HR 2.91, 95 % CI 1.60-5.31, p < 0.0005) were independent risk factors associated with all-cause death during a median follow-up of 31 months. In outpatients with HF and RD, a higher BUN/Cr and lower eGFR are reliable renal biomarkers for caval congestion. The BUN/Cr is associated with long-term mortality and may help to stratify HF severity

Cardiorenal interactions in heart failure - insights from recent therapeutic advances

Heart failure is a syndrome that may develop when cardiovascular disease progresses or is insufficiently treated and associated with a poor quality of life, high mortality rates and increased health care expenditures. Prevention and treatment of heart failure is therefore of utmost importance. New therapies in patients with cardiovascular disease have recently been shown to be effective in the prevention and sometimes treatment of heart failure, and additional research is underway. Specifically, in high risk patients with either (a combination of) diabetes, chronic kidney disease and/or heart failure, three specific drug classes (sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon like peptide 1 receptor agonists (GLP-1-RA) and non steroidal mineralocorticoid receptor antagonists (MRA)) have taken center stage in therapeutic approach for these high cardiovascular risk patients. The commonality of these drugs is the finding that they improve cardiovascular and renal endpoints across the cardiorenal continuum, SGTL2i have already proven effective in all subtypes of heart failure, while we await data on non steroidal MRA therapy in heart failure. The story may be different for GLP-1-RA in patients with established heart failure, but these drugs are effective in reducing cardiovascular events in patients with diabetes. Taken together, these new therapies advance the treatment and improve the associated outcomes of patients with cardiorenal disease and diabetes, with similar characteristics and effectiveness in different conditions.</p

Analysis of nanoprecipitation effect on toughness behavior in warm worked AA7050 alloy

Commonly adopted main methods aimed to improve the strength–toughness combination of high strength aluminum alloys are based on a standard process. Such a process includes alloy solution heat treatment, water-quench and reheating at controlled temperature for ageing holding times. Some alloys request an intermediate cold working hardening step before ageing for an optimum strength result. Recently a warm working step has been proposed and applied. This replaces the cold working after solution treatment and quenching and before the final ageing treatment. Such an alternative process proved to be very effective in improving strength–toughness behavior of 7XXX aluminum alloys. In this paper the precipitation state following this promising process is analyzed and compared to that of the standard route. The results put in evidence the differences in nanoprecipitation densities that are claimed to be responsible for strength and toughness improved properties