Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF

Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF

Atomically dispersed Pt-N-4 sites as efficient and selective electrocatalysts for the chlorine evolution reaction

Chlorine evolution reaction (CER) is a critical anode reaction in chlor-alkali electrolysis. Although precious metal-based mixed metal oxides (MMOs) have been widely used as CER catalysts, they suffer from the concomitant generation of oxygen during the CER. Herein, we demonstrate that atomically dispersed Pt-N-4 sites doped on a carbon nanotube (Pt-1/CNT) can catalyse the CER with excellent activity and selectivity. The Pt-1/CNT catalyst shows superior CER activity to a Pt nanoparticle-based catalyst and a commercial Ru/Ir-based MMO catalyst. Notably, Pt-1/CNT exhibits near 100% CER selectivity even in acidic media, with low Cl- concentrations (0.1M), as well as in neutral media, whereas the MMO catalyst shows substantially lower CER selectivity. In situ electrochemical X-ray absorption spectroscopy reveals the direct adsorption of Cl- on Pt-N-4 sites during the CER. Density functional theory calculations suggest the PtN4C12 site as the most plausible active site structure for the CER

'Time is prognosis' in heart failure: time-to-treatment initiation as a modifiable risk factor.

In heart failure (HF), acute decompensation can occur quickly and unexpectedly because of worsening of chronic HF or to new-onset HF diagnosed for the first time ('de novo'). Patients presenting with acute HF (AHF) have a poor prognosis comparable with those with acute myocardial infarction, and any delay of treatment initiation is associated with worse outcomes. Recent HF guidelines and recommendations have highlighted the importance of a timely diagnosis and immediate treatment for patients presenting with AHF to decrease disease progression and improve prognosis. However, based on the available data, there is still uncertainty regarding the optimal 'time-to-treatment' effect in AHF. Furthermore, the immediate post-worsening HF period plays an important role in clinical outcomes in HF patients after hospitalization and is known as the 'vulnerable phase' characterized by high risk of readmission and early death. Early and intensive treatment for HF patients in the 'vulnerable phase' might be associated with lower rates of early readmission and mortality. Additionally, in the chronic stable HF outpatient, treatments are often delayed or not initiated when symptoms are stable, ignoring the risk for adverse outcomes such as sudden death. Consequently, there is a dire need to better identify HF patients during hospitalization and after discharge and treating them adequately to improve their prognosis. HF is an urgent clinical scenario along all its stages and disease conditions. Therefore, time plays a significant role throughout the entire patient's journey. Therapy should be optimized as soon as possible, because this is beneficial regardless of severity or duration of HF. Time lavished before treatment initiation is recognized as important modifiable risk factor in HF

Microanatomy and growth of the mesosaurs <i>Stereosternum tumidum</i> and <i>Brazilosaurus sanpauloensis</i> (Reptilia, Parareptilia)

Histology and microanatomy of vertebrae, ribs, haemal arch, and humeri and femora of 10 individuals of Stereosternum and two dorsal ribs of 1 individual of Brazilosaurus were studied. All individuals had achieved a body length of 50&thinsp;cm (equal to 65&thinsp;% of the maximum known body length) or larger. All sampled bones are highly osteosclerotic due to the reduction of medullary cavities and the filling of medullary regions by endosteal bone. Calcified cartilage occurs – if at all – only locally in small clusters in the medullary regions of midshaft and in higher amounts only in non-midshaft sections of long bones and towards the medio-distal rib shaft, respectively. The primary bone tissue consists of highly organized parallel-fibred tissue and/or lamellar tissue, which is in most samples relatively lightly vascularized or even avascular. If present, vascular canals are mainly longitudinally oriented; some show a radial orientation. Simple vascular canals as well as primary osteons occur. Some of the latter are secondarily altered, i.e. widened. Remodelling of the periosteal cortex is only documented by few scattered erosion cavities and secondary osteons. The tissue is regularly stratified by lines of arrested growth (LAGs), which usually appear as double or multiple rest lines, indicating strong dependence on exogenous and endogenous factors. Because of the inhibition of periosteal remodelling the growth record is complete and no inner cycles are lost. Individuals of Stereosternum show a poor correlation of body size and number of growth marks, which might be the result of developmental plasticity. Brazilosaurus shows a highly organized, avascular lamellar tissue and a high number of regularly deposited rest lines throughout the cortex of the ribs. The medullary region in the ribs of Brazilosaurus is distinctly larger when compared to ribs of Stereosternum. However, strong osteosclerosis is obvious in both taxa, pointing to a high degree of aquatic adaption. Ribs of Stereosternum, Brazilosaurus, and Mesosaurus are clearly distinguishable from each other by the distribution of the periosteal and endosteal territory. Furthermore, Brazilosaurus differs in its growth pattern (i.e. spacing of rest lines) when compared to Stereosternum and Mesosaurus.</p

Elektronisches Auge / MIRIS. Demonstrator zur Sortierung von recyclebarem Spezialmuell am Beispiel von Altpapier Abschlussbericht

Available from TIB Hannover: F98B1321+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Transition in pediatric rheumatology- experiences from the pediatric rheumatismcenter Sankt Augustin

BackgroundTransition is ajoint effort of the young patients, their families and the attending pediatric and adult rheumatologists. The quality of the transitional process for patients with rheumatic diseases was retrospectively reviewed using astandardized questionnaire. Patients were transferred to rheumatologists for adult care through personal contact, if possible.MethodsInclusion criteria were: diagnosis of chronic inflammatory rheumatic joint disease or systemic rheumatic disease, duration of care for >2years in the pediatric rheumatology center and 2presentations at the age of 17-18years. Atelephone interview was performed using astandardized questionnaire on the type of care, medication, diagnosis, satisfaction with the care and the transition process.ResultsOf the 62 enrolled patients 50 (81%) had juvenile idiopathic arthritis (JIA). In total, 40patients (65%) were seen by an adult rheumatologist on aregular basis. Reasons for discontinuation of medical care were mainly freedom of symptoms, lack of time and non-compliance. Before and after transition, 15 and 9 patients, respectively were treated with conventional disease-modifying antirheumatic drugs (DMARD) and 27 and 27, respectively with biologics. The subjective assessment of medical care in pediatric rheumatology was (mean +/- SD) 9.3 +/- 1.05, in adult rheumatology 7.6 +/- 1.1 and the satisfaction with the transition process was 7.7 +/- 2.1. Problem issues mentioned by some patients were lack of time with the rheumatologist and long waiting periods for appointments.DiscussionIndividual transfer of patients from pediatric to adult rheumatology care was associated with a high degree of satisfaction in this analysis. Change of diagnosis or an unexpected termination of rheumatology treatment was not detected

Palaeontological evidence reveals convergent evolution of intervertebral joint types in amniotes

© 2020, The Author(s). The intervertebral disc (IVD) has long been considered unique to mammals. Palaeohistological sampling of 17 mostly extinct clades across the amniote tree revealed preservation of different intervertebral soft tissue types (cartilage, probable notochord) seen in extant reptiles. The distribution of the fossilised tissues allowed us to infer the soft part anatomy of the joint. Surprisingly, we also found evidence for an IVD in fossil reptiles, including non-avian dinosaurs, ichthyosaurs, plesiosaurs, and marine crocodiles. Based on the fossil dataset, we traced the evolution of the amniote intervertebral joint through ancestral character state reconstruction. The IVD evolved at least twice, in mammals and in extinct diapsid reptiles. From this reptilian IVD, extant reptile groups and some non-avian dinosaurs independently evolved a synovial ball-and-socket joint. The unique birds dorsal intervertebral joint evolved from this dinosaur joint. The tuatara and some geckos reverted to the ancestral persisting notochord