Heart failure outcomes in patients with type 2 diabetes mellitus: findings from the cardiovascular outcome trials of antidiabetes agents

Type 2 diabetes mellitus (T2DM) is a recognised risk factor for several cardiovascular (CV) conditions including heart failure (HF). Findings that reflect CV risk associated with T2DM medications have led to regulatory requirement of conducting CV outcome trials (CVOTs) for new antidiabetes drugs. Over the years, several CVOTs using different glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors have reported neutral or improved CV risks or hospitalisation for HF. However, these studies included only a small proportion of the patients with baseline HF thus limiting the available evidence. Ongoing trials such as EMPEROR programme and DAPA-HF in large patient populations with chronic HF could potentially broaden the use of these drugs beyond their conventional therapeutic indication

Vorhofflimmerndiagnostik mittels EKG-fähiger Smartwatches

Background!#!The fiberoptic endoscopic evaluation of swallowing (FEES) is considered to be an indispensable instrumental procedure in the management of patients with dysphagia. The aim of the implemented training curriculum is to raise the quality standards and to contribute to an upgrading of the procedure.!##!Objective!#!The study evaluated to what extent a standardized implementation, evaluation and documentation of FEES takes place in Germany after the introduction of the curriculum.!##!Material and methods!#!In this study 603 neurological and geriatric hospitals in Germany were interviewed by the use of an online questionnaire regarding structural features and the course of the investigation.!##!Results!#!A total of 190 institutions completed the survey. Of the institutions 43.31% had only implemented FEES since the publication of the curriculum. The practical application is increasingly carried out by physicians (59%), the clinical reports and cost recommendations are carried out by speech therapists (62% and 83%, respectively). The practical application by speech therapists increases with increasing level of training. Despite orientation towards the standard protocol according to Langmore, there are differences in the implementation of the anatomical physiological examination, the consistencies and foods administered and the scoring of swallowing-relevant parameters.!##!Discussion!#!The introduction of the curriculum has led to an upgrading of the FEES and to a strengthening of speech therapy as the implementing professional group. At the current state of the art there is a homogeneous course of the examination in essential aspects but it shows a need for further uniformity. The FEES curriculum could be used as a guiding instrument for further standardization

Effects of hormonal changes on sarcopenia in chronic kidney disease: where are we now and what can we do?

Sarcopenia or muscle wasting is a progressive and generalized skeletal muscle disorder involving the accelerated loss of muscle mass and function, often associated with muscle weakness (dynapenia) and frailty. Whereas primary sarcopenia is related to ageing, secondary sarcopenia happens independent of age in the context of chronic disease states such as chronic kidney disease (CKD). Sarcopenia has become a major focus of research and public policy debate due to its impact on patient's health-related quality of life, health-care expenditure, morbidity, and mortality. The development of sarcopenia in patients with CKD is multifactorial and it may occur independently of weight loss or cachexia including under obese sarcopenia. Hormonal imbalances can facilitate the development of sarcopenia in the general population and is a common finding in CKD. Hormones that may influence the development of sarcopenia are testosterone, growth hormone, insulin, thyroid hormones, and vitamin D. Although the relationship between free testosterone level that is low in uraemic patients and sarcopenia in CKD is not well-defined, functional improvement may be seen. Unlike testosterone, it is known that vitamin D is associated with muscle strength, muscle size, and physical performance in patients with CKD. Outcomes after vitamin D replacement therapy are still controversial. The half-life of growth hormone (GH) is prolonged in patients with CKD. Besides, IGF-1 levels are normal in patients with Stage 4 CKD-a minimal reduction is seen in the end-stage renal disease. Unresponsiveness or resistance of IGF-1 and changes in the GH/IGF-1 axis are the main causes of sarcopenia in CKD. Low serum T3 level is frequent in CKD, but the net effect on sarcopenia is not well-studied. CKD patients develop insulin resistance (IR) from the earliest period even before GFR decline begins. IR reduces glucose utilization as an energy source by hepatic gluconeogenesis, decreasing muscle glucose uptake, impairing intracellular glucose metabolism. This cascade results in muscle protein breakdown. IR and sarcopenia might also be a new pathway for targeting. Ghrelin, oestrogen, cortisol, and dehydroepiandrosterone may be other players in the setting of sarcopenia. In this review, we mainly examine the effects of hormonal changes on the occurrence of sarcopenia in patients with CKD via the available data

PREVENTT: preoperative intravenous iron to treat anaemia in major surgery: study protocol for a randomised controlled trial.

BACKGROUND: Anaemia is common in patients undergoing major surgery. The current standard of care for patients with low haemoglobin in the peri-operative period is blood transfusion. The presence of preoperative anaemia is associated with an increased likelihood of the patient receiving peri-operative transfusion and worsened outcomes following surgery, more post-operative complications, delayed recovery and greater length of hospital stay. Intravenous iron, if applied in the preoperative setting, may correct anaemia by the time of surgery and reduce the need for blood transfusion and improve outcomes. METHODS/DESIGN: PREVENTT is a phase III double-blind randomised controlled trial that will compare the use of intravenous ferric carboxymaltose (dose 1000 mg) with placebo 10-42 days before major open abdominal surgery in 500 patients with anaemia (haemoglobin < 120 g/L). The primary outcome measure will be the need for blood transfusion and secondary endpoints will include post-operative recovery, length of hospital stay, health care utilisation and cost analysis. TRIAL REGISTRATION: ISRCTN67322816--registered 9 October 2012. ClinicalTrials.gov identifier: NCT01692418

Neurological and endocrinological disorders: orphans in chronic obstructive pulmonary disease

SummaryPatients with chronic obstructive pulmonary disease (COPD) are often characterised by a range of characteristic co-morbidities that interfere with their pulmonary disease. In addition to a mere association with co-morbidities, a complex pathophysiological interaction and mutual augmentation occurs between COPD and its co-morbidities that may result in disease progression and increased morbidity and mortality. An interdisciplinary approach is required both for diagnosis and treatment to target co-morbidities early in the course of the disease. This review summarizes the current knowledge of the interaction with cerebrovascular disease and endocrinological co-morbidities in COPD patients. There is growing evidence that COPD is an independent risk factor for ischemic stroke, increasing the risk about twofold. Stroke risk in COPD patients increases with the severity of the disease as measured by the degree of airflow limitation. The presence of cardiovascular risk factors is of particular importance for stroke prevention in COPD patients. Endocrinological co-morbidities are also important and many are associated with increased cardiovascular risk. Impaired glucose metabolism ranges from insulin resistance to overt diabetes mellitus, which is a frequent finding and is associated with worse outcome

IGF-1 treatment reduces weight loss and improves outcome in a rat model of cancer cachexia

Background: A hallmark symptom of cancer cachexia is the loss of skeletal muscle. This is at least partially due to a deregulation of the growth hormone/IGF-1 axis and a subsequently impaired protein synthesis in skeletal muscle. Here, we investigated the effect of IGF-1 supplementation in a rat model of cancer cachexia. Methods: Juvenile rats were inoculated with the Yoshida AH-130 hepatoma and treated once daily with 0.3 mg kg−1 day−1 (low dose) or 3 mg kg−1 day−1 (high dose) IGF-1 or placebo for a period of maximal 16 days. Body weight and body composition (by NMR) were assessed at baseline and at the end of the study or day of death. Locomotor activity and food intake were assessed at baseline and day 10/11 after tumour inoculation for 24 h. Results: Untreated tumour-bearing rats lost 55.3 ± 2.14 g body weight, which was reduced by low-dose to −39.6 ± 11.1 g (p = 0.0434) and high-dose IGF-1 to −42.7 ± 8.8 g (p = 0.057). Placebo-treated rats lost 41.4 ± 2.0-g lean mass, which was attenuated by low-dose IGF-1 (−28.8 ± 8.3 g, p = 0.041) and high-dose IGF-1 (−30.9 ± 7.4, p = 0.067). Spontaneous activity and food intake were improved by low-dose IGF-1 only. No effect on fat mass was observed. Low-dose IGF-1 significantly reduced mortality (HR = 0.45, 95%CI = 0.21–0.93, p = 0.0315), whilst the high dose did not reach significance (HR = 0.68, 95%CI = 0.26–1.74, p = 0.42). Conclusion: Low-dose IGF-1 reduced mortality and attenuated loss of body weight as well as muscle mass in the Yoshida hepatoma rat model. Moreover, an improved quality of life was observed in these animals. Further experiments using different doses are necessary

Ursodeoxycholic acid treatment in a rat model of cancer cachexia

UDCA treatment in the Yoshida hepatoma model showed a trend towards attenuation of tissue loss in animals with progressive weight loss in cancer cachexia. Tumor growth and activity indicators were not altered. Both doses of UDCA tended to reduce the mortality rates in tumor-bearing animals. Larger studies with longer follow-up are required to verify these findings

Advanced cancer is also a heart failure syndrome: a hypothesis

We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti-cancer therapies. This includes an increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilatation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways. We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti-cancer therapies. The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients. We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio-oncology