Atomic Displacements Enabling the Observation of the Anomalous Hall Effect in a Non-Collinear Antiferromagnet.

Antiferromagnets with non-collinear spin structures display various properties that make them attractive for spintronic devices. Some of the most interesting examples are an anomalous Hall effect despite negligible magnetization and a spin Hall effect with unusual spin polarization directions. However, these effects can only be observed when the sample is set predominantly into a single antiferromagnetic domain state. This can only be achieved when the compensated spin structure is perturbed and displays weak moments due to spin canting that allows for external domain control. In thin films of cubic non-collinear antiferromagnets, this imbalance is previously assumed to require tetragonal distortions induced by substrate strain. Here, it is shown that in Mn3 SnN and Mn3 GaN, spin canting is due to structural symmetry lowering induced by large displacements of the magnetic manganese atoms away from high-symmetry positions. These displacements remain hidden in X-ray diffraction when only probing the lattice metric and require measurement of a large set of scattering vectors to resolve the local atomic positions. In Mn3 SnN, the induced net moments enable the observation of the anomalous Hall effect with an unusual temperature dependence, which is conjectured to result from a bulk-like temperature-dependent coherent spin rotation within the kagome plane.

COPD: Rethinking Patient Management - How to Approach a Challenging Patient Group Successfully.

In comparison to other chronically ill people, patients suffering from chronic obstructive pulmonary disease (COPD) have many additional difficulties to face and conquer. Due to the contribution of avoidable causes of their illness ("smokers' lung"), society holds people with COPD responsible for their disease, which in return often leads to stigmatization and social isolation. In addition, COPD patients commonly belong to a less privileged social class, own a low socioeconomic status, and lower education. Their physical symptoms are easily observable and - by employing moderate adherence - treatable. Nonetheless, the influence of COPD on a patient's psyche often plays an overly prominent role during therapy. "There is only half a patient laying on the examination table," a revelation that sums up the current state of COPD research and the result of the expert meeting "Luftschlösser" ("castles in the clouds"), which took place in spring 2018. Within the limits of the meeting, participants identified practically applicable approaches aiming to enhance the patient management of this challenging patient group. These considerations are supposed to support healthcare professionals in their daily work and aim to improve the therapy as well as the outcome for COPD patients.

Vitamin D supplementation of 4000 IU daily and cardiac function in patients with advanced heart failure: The EVITA trial.

BACKGROUND: Data regarding the effects of vitamin D on cardiac function are inconclusive. METHODS: In a post-hoc analysis of the EVITA (Effect of vitamin D on mortality in heart failure) trial, we investigated whether a daily vitamin D3 supplement of 4000 IU for three years affects echocardiography parameters like left ventricular end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), and LV ejection fraction (LVEF) in patients with advanced heart failure (HF) and 25­hydroxyvitamin D levels <75 nmol/L. Of 400 patients enrolled, 199 were assigned to vitamin D and 201 to placebo. We assessed time × treatment interaction effects using linear mixed models and analyzed in subgroups vitamin D effects at 12 and 36 months post-randomization using analysis of covariance with adjustments for baseline values. RESULTS: At baseline, values of LVEDD, LVESD, and LVEF were 67.5 ±â€¯10.5 mm, 58.9 ±â€¯12.0 mm, and 30.47 ±â€¯10.2%, respectively. There were no time × treatment interaction effects on LV echocardiographic parameters in the entire study cohort, neither at 12 months nor at 36 months post-randomization (P-values > 0.05). However, in the subgroup of patients aged ≥50 years, vitamin D treatment was associated with an increase in LVEF of 2.73% (95%CI: 0.14 to 5.31%) at 12 months post-randomization (n = 311). The increase was slightly attenuated to 2.60% (95%CI: -2.47 to 7.67%) at 36 months post-randomization (n = 242). CONCLUSION: Our data indicate that vitamin D supplementation does not significantly improve cardiac function in all patients with advanced HF. However, vitamin D probably improves LV function in HF patients aged ≥50 years.

Vitamin D supplementation and bone turnover in advanced heart failure: the EVITA trial.

Low vitamin D status is common in patients with heart failure and may influence bone health. A daily vitamin D dose of 4000 IU (moderately high dose) for 3 years had however no effect on parameters of bone metabolism, even in patients with very low vitamin D status. INTRODUCTION: Low vitamin D status is common in patients with heart failure (HF) and has been related to disturbed bone turnover. The present study investigated the effect of a daily vitamin D3 dose of 4000 IU on bone turnover markers (BTMs) in patients with advanced HF and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L. METHODS: In this pre-specified secondary analysis of a randomized controlled trial, we assessed in 158 male HF patients (vitamin D group: n = 80; placebo group: n = 78) between-group differences in calciotropic hormones (25OHD, 1,25-dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone [iPTH]), and BTMs (cross-linked C-telopeptide of type I collagen, bone-specific alkaline phosphatase, undercarboxylated osteocalcin). Comparisons were performed at the end of a 3-year vitamin D supplementation period with adjustments for baseline values. RESULTS: Compared with placebo, vitamin D increased 25OHD on average by 54.3 nmol/L. At study termination, 25OHD and 1,25(OH)2D were significantly higher (P < 0.001 and P = 0.007, respectively), whereas iPTH tended to be lower in the vitamin D group than in the placebo group (P = 0.083). BTMs were initially within their reference ranges and did not differ significantly between groups at study termination, neither in the entire study cohort nor when data analysis was restricted to the subgroup of patients with initial 25OHD concentrations < 30 nmol/L (n = 54) or to patients with initial hyperparathyroidism (n = 65) (all P values > 0.05). CONCLUSIONS: A daily vitamin D3 dose of 4000 IU did not influence BTMs. Data indicate that vitamin D supplementation will not lower bone turnover in male patients with heart failure.

Reconstruction of the bony chin using sagittal split osteotomies of the remaining mandible - A new technique for a special indication: Case report.

There are several indications for resecting the bony chin, such as squamous cell carcinoma, sarcoma, or benign tumors of the jaw such as ameloblastoma. Several techniques for reconstruction of the bony chin, such as the use of metal plates and also revascularized free bone grafts of the iliac crest, fibula, or scapula, are common. In the case of poor vascular supply, however, alternative techniques may be necessary. In this report, a new technique is described using pedicled bone flaps from both sagittally split mandibular stumps following chin resection. These flaps were pedicled on the mylohyoid muscles and advanced to restore the continuity of the mandible. An advantage of this procedure was minimization of the soft tissue defect, making repair easier. Morbidity of the resection and reconstruction was thus reduced, and recovery of the patient was very quick.

Randomized supplementation of 4000 IU vitamin D3 daily vs placebo on the prevalence of anemia in advanced heart failure: the EVITA trial.

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels (< 75 nmol/l) are inversely associated with anemia prevalence. Since anemia and low 25OHD levels are common in patients with heart failure (HF), we aimed to investigate whether vitamin D supplementation can reduce anemia prevalence in advanced HF. METHODS: EVITA (Effect of Vitamin D on Mortality in Heart Failure) is a randomized, placebo-controlled clinical trial in patients with initial 25OHD levels < 75 nmol/l. Participants received either 4000 IU vitamin D3 daily or a matching placebo for 36 months. A total of 172 patients (vitamin D group: n = 85; placebo group: n = 87) were investigated in this pre-specified secondary data analysis. Hemoglobin (Hb) and other hematological parameters were measured at baseline and study termination. Assessment of between-group differences in anemia prevalence and Hb concentrations was performed at study termination, while adjusting for baseline differences. RESULTS: In the vitamin D and placebo group, baseline proportions of patients with anemia (Hb < 12.0 g/dL in females and < 13.0 g/dL in males) were 17.2% and 10.6%, respectively (P = 0.19). At study termination, the proportion of patients with anemia in the vitamin D and placebo groups was 32.2% and 31.8%, respectively (P > 0.99). There was no between-group difference in change in the Hb concentrations (- 0.04 g/dL [95%CI:-0.53 to 0.45 g/dL]; P = 0.87). Results regarding anemia risk and Hb concentrations were similar in the subgroup of patients with chronic kidney disease (vitamin D group: n = 26; placebo group: n = 23). Moreover, results did not differ substantially when data analysis was restricted to patients with deficient baseline 25OHD levels. CONCLUSIONS: A daily vitamin D supplement of 4000 IU did not reduce anemia prevalence in patients with advanced HF. Data challenge the clinical relevance of vitamin D supplementation to increase Hb levels. TRIAL REGISTRATION: The study was registered at EudraCT (No. 2010-020793-42) and clinicaltrials.gov ( NCT01326650 ).

Treatment of Cardiovascular Risk Factors in Women.

Cardiovascular disease (CVD) is a leading cause of death for both women and men. Common traditional risk factors for CVD, such as hypercholesterolemia, hypertension and smoking have a high prevalence in women and in some cases a greater health impact compared with men. Nevertheless, risk factors are treated less often and less aggressively in women than in men, partly due to decreased awareness on the part of public health opinion makers, patients and physicians. About seventy five percent of all coronary heart disease deaths among women could be avoided if CVD risk factors like hypercholesterolemia, hypertension and smoking are adequately treated. This narrative review discusses the treatment of the 4 CVD risk factors, namely hypercholesterolemia, hypertension, smoking and diabetes. These risk factors were examined in the Framingham Heart study and years later they were found in the INTERHEART study to be the 4 most important risk factors for the development of CVD.

[New oral anticoagulants: who really needs them?]. / Neue orale Antikoagulanzien: Wer braucht sie wirklich?

The new oral anticoagulants (NOAC) are alternative drugs to classical vitamin K antagonists (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation. They have been shown in randomized trials to be superior to warfarin in reducing clinical endpoints, although at rather small effect sizes. However, in study centers with good anticoagulation management their superiority was barely significant. The effectiveness of anticoagulation therapy is crucially dependent on individual drug adherence. NOAC potentially decrease adherence due to several reasons, among them the twice-daily dosing requirement in some of them and the nonnecessity for anticoagulation monitoring. Anticoagulation monitoring is assumed to increase adherence per se. VKA are potentially better suitable to compensate for low adherence due to their long half-lives.

Pulmonary hypertension in COPD.

Pulmonary hypertension (PH) is a common consequence of COPD. It has been speculated that patients showing serious PH and vascular remodeling without severe airway obstruction might benefit from vasoactive treatment. There is no approved drug available for COPD-induced PH. Most trials assessing the efficacy of vasoactive drugs in PH have had a follow-up of 12-16 weeks. We report on 4 subjects with COPD and PH. Pulmonary arterial hypertension associated diseases and pulmonary embolism were ruled out. PH persisted despite optimized treatment of underlying COPD and comorbidities, so bosentan was started in all 4 subjects. With bosentan the mean pulmonary artery pressure improved. The average gains in 6-min walk distance at 2-3 months and 8-9 months were 36 m and 145 m, respectively. The maximum gains in 6-min walk distance of the individual subjects were at the 9th, 13th, and 18th month. Oxygenation was stable, and no side effects were observed. We suggest from this experience that in clinical trials of PH in COPD, a follow-up of 16 weeks might cause underestimation of the treatment effects.

Role of physician gender in drug therapy.

There is evidence that female patients receive less intensified drug therapy in many medical conditions than male patients. However, there are only limited data regarding the influence of physician gender on drug therapy. It has been shown, for example, that female physicians tend to adhere more closely to guideline-recommended pharmacotherapy compared to their male counterparts. In some medical conditions where drug therapy is only one among various components of a complex interplay of therapeutic regimes (e.g., diabetes, cardiovascular diseases, depression, pain management), female physicians seem to achieve better overall intermediate outcomes and some studies suggest that "better" drug therapy is provided by female compared to male physicians. The reasons for the overall better outcomes may be superior communication skills of female physicians, participatory decision making, and consequently improved drug adherence in addition to or in combination with more effective non-pharmacologic treatment results. It is impossible to distinguish between the individual contributions of drug- and nondrug-related influence on such improved outcomes and thus to determine whether they are due to unconfounded physician gender effects on drug therapy. There is until now in no area of medicine evidence to suggest that a patient will consistently receive higher quality of drug therapy by switching to a physician of a specific gender.

[New oral anticoagulants for the prevention of stroke. Open questions in geriatric patients]. / Neue orale Antikoagulanzien zur Schlaganfallprävention. Offene Fragen bei geriatrischen Patienten.

New oral anticoagulants for the prevention of stroke in patients with nonvalvular atrial fibrillation have been available for a few months, among them the reversible direct thrombin inhibitor dabigatran and the factor Xa antagonist rivaroxaban. These drugs are considered by some as a superior alternative to vitamin K antagonists. The lack of necessity for regular monitoring is advertised as a major advantage. Although atrial fibrillation is a disease with increasing prevalence with higher age, the suitability of the new drugs has not been extensively studied in multimorbid geriatric patients. Since dabigatran is contraindicated in patients with renal insufficiency, only the lower of the two approved dosages can usually be prescribed in elderly patients. For the lower dosage, however, no superiority in prevention of stroke has been documented but merely a reduction in major bleeding rates, although at a high number needed to treat. The requirement for a twice-daily dosage regimen, the lack of an anticoagulation monitoring option, the relatively short duration of action and the lack of an antidote may even prove to be crucial disadvantages in clinical practice in comparison to vitamin K antagonists. Until more data are available, the new oral anticoagulants should be prescribed with caution in geriatric patients.

Role of physician gender in the quality of care of cardiometabolic diseases.

Evidence suggests that patient gender is associated with the quality of care provided in the treatment of cardiometabolic diseases. The majority of findings suggest that female patients receive less intensified care than male patients. However, the question whether physician gender plays a role in the quality of care has been debated for some time. For example, it has been postulated that the practice styles of female physicians, such as spending more time with a patient, hearing and listening more effectively, and including more preventive measures, may result in more efficient clinical encounters that may positively affect clinical outcomes. This narrative review examines the existing evidence regarding the effects of physician gender on the quality of care provided, focusing mainly on patients with cardiometabolic diseases.

Antisense oligonucleotides for the treatment of dyslipidemia.

New studies further demonstrate that lowering low-density lipoprotein (LDL)-cholesterol, at least with the use of statins, decreases the risk of cardiovascular disease (CVD). Subsequently national and international guidelines have set target levels for LDL-cholesterol that are progressively lower, making the likelihood of patients attaining them progressively more limited, even with the use of all currently available medications. Thus, there is a clear need for new therapeutic approaches to lower LDL-cholesterol. Antisense oligonucleotides (ASO) represent a new paradigm for the discovery of potentially powerful and selective drugs with a mechanism of action based on the concept of base-pair hybridizazion as described by Watson and Crick, resulting in decreased production of target proteins. In mouse and human genetic models it has been shown that decreasing hepatic apolipoprotein B-100 (ApoB-100) as well as proprotein convertase subtilisin/kexin type 9 (PCSK9) production is associated with lower circulating LDL-cholesterol levels. Purpose of this review is to discuss the available data on the effects of various ASO used for the treatment of dyslipidemia, with the main focus on ASO against ApoB-100, the most advanced in clinical development, and on PCSK9.

The whey fermentation product malleable protein matrix decreases triglyceride concentrations in subjects with hypercholesterolemia: a randomized placebo-controlled trial.

Malleable protein matrix (MPM) is a unique whey-derived ingredient obtained through a fermentation process using proprietary lactic acid bacteria strains from the Lactobacillus kefiranofaciens species. Because evidence from animal models suggests that MPM decreases serum lipid concentrations, the purpose of the present trial was to assess the hypothesis that MPM exerts lipid-lowering effects in humans. A total of 161 subjects (50% male; age 54.5 ± 9.8 yr, body mass index 26.3 ± 3.6 kg/m(2)) with hypercholesterolemia with baseline low-density lipoprotein cholesterol (LDL-C) levels of 181 ± 30 mg/dL and normal triglyceride (TG) levels (131 ± 55 mg/dL) were randomized to receive MPM (2 × 15 g/d) or matching placebo. A 6-wk run-in phase was followed by a double-blind 12-wk treatment phase after randomization. The data were analyzed on an intention-to-treat basis. The primary outcome measure was the percentage change of LDL-C. The secondary outcome measures were changes in TG and high-density lipoprotein cholesterol concentrations as well as changes in other cardiovascular risk factors. After 12 wk of treatment, the relative TG decrease from baseline reached 9.8%, whereas LDL-C was slightly decreased (by 1.5%) following MPM treatment compared with placebo in the intention-to-treat cohort. The treatment effect on TG reduction was much higher in the subset of subjects having TG levels at baseline of 150 mg/dL or above (n=42), reaching 20.0% compared with placebo. High-density lipoprotein cholesterol concentrations, blood pressure, and fasting blood glucose remained unchanged, whereas a positive treatment effect was seen on hemoglobin A(1c). The MPM product was tolerated well without severe adverse events. In conclusion, MPM has significant TG-lowering properties in subjects with combined hypercholesterolemia and higher TG levels. Its effects on LDL-C concentrations and glucose metabolism deserve further investigation.

Atherosclerotic disease location and disparities in the control and treatment of cardiovascular risk factors in patients with Type 2 diabetes.

AIMS: To assess whether differences exist in the control and intensity of medication treatment of cardiovascular risk factors in secondary prevention patients with Type 2 diabetes, depending on their atherosclerotic disease territory [coronary artery disease (CAD), cerebrovascular disease (CBVD) or peripheral arterial disease (PAD)]. METHODS: Cross-sectional analysis of 17 571 patients with Type 2 diabetes with prevalent atherosclerotic disease. Endpoints included uncontrolled cardiovascular disease (CVD) risk factors [systolic blood pressure (SBP) > or = 140 mmHg, low-density lipoprotein cholesterol > or = 3.4 mmol/l and glycated haemoglobin > or = 8.0%] and high intensity of medication treatment (defined as > or = 2 classes of anti-hypertensive agents, > or = 1 lipid-lowering agent or either insulin or > or = 2 oral glucose-lowering agents) in patients with uncontrolled CVD risk factors. Multiple-adjusted odds ratios were calculated for CAD, CBVD and PAD after adjusting for sex, age, body mass index, current smoking and diabetes duration. RESULTS: Proportions of patients with uncontrolled risk factors were significantly different among disease territories. Decreased odds of having lipids not controlled were observed in patients with CAD, while decreased odds of having systolic blood pressure not controlled were observed in patients with PAD. PAD was associated with the highest odds of hyperglycaemia not being controlled. High-intensity treatment was observed in lipid and blood glucose management but not in hypertension management, independent of disease location. CONCLUSIONS: In subjects with Type 2 diabetes and atherosclerotic disease, control of modifiable CVD risk factors but not intensity of medication treatment is modified by atherosclerotic disease territory. Intensity of medication treatment is different between risk factors.

[Drug therapy in the elderly :what are the problems? What are the dos and don'ts?]. / Arzneimitteltherapie im Alter : Wo liegen die Probleme? Was soll man tun, was muss man lassen?

With increasing age a clear increase in drug use exists in parallel with the age-related burden of disease. Elderly subjects have more frequent and more severe adverse drug reactions. Often polypharmacy causes a cascade which leads to the prescription of additional drugs to treat adverse drug reactions. To ensure safe medications, consideration of physiological changes and their relevance for pharmacodynamics and pharmacokinetics is necessary, as are critical prescription decisions with clearly defined individual therapeutic targets. Geriatric assessments should be performed more often. They comprise assessments of activities of daily living, the degree of autonomy and self-sufficiency, cognitive and nutritional status. Chronological age is only a minor criterion for prescription decisions. Practical help (dispensing devices, help when visual, tactile or cognitive impairments are present) will be able to improve adherence and thus safety and efficacy of drugs. Recognizing and preventing adverse drug reactions is probably the single most reversible affliction of geriatric medicine. Lists with potentially inappropriate medications (PIM) in the elderly are rather unsuitable due to their categorical character. Better consideration of patient-related factors and defining "potentially inappropriate patients (PIP)" seems preferable for preventing the prescription of risk-entailing medications.

Huge liposarcoma of the left retroperitoneum.

Liposarcoma is one of the most common soft-tissue sarcomas. Unless it grows to massive proportions, it rarely causes symptoms. A 64-year-old man presented with weight loss, asthenia, and increasing abdominal girth caused by a large liposarcoma in the left retroperitoneum. Despite resection with sarcoma-free margins and intensive follow-up evaluation, he died of a tumor recurrence 2 years later. Complete surgical resection of the liposarcoma is the only curative option, but establishing a prognosis remains a challenge.

Designing a study to evaluate the effect of apheresis in patients with elevated lipoprotein(a).

Lipoprotein(a) (Lp(a)) is a risk factor for premature coronary artery disease. Lp(a) levels can neither be influenced sufficiently by standard hypolipemic diet nor by drug therapy. Currently, lipid apheresis is the only option to effectively lower Lp(a) levels in patients with elevated Lp(a) and progressive CVD. The lipid-clinic at the Charité University hospital Berlin and other German apheresis centres have longstanding positive experience with this therapeutic regimen. Lately, in Germany lipid apheresis was accepted as the treatment of choice for patients with elevated Lp(a) levels > 60 mg/dl and progressive CVD. At the same time, care providers were obliged to conduct a controlled trial to prove the efficacy of lipid apheresis for this indication. Therefore, we designed a prospective, randomized, controlled trial to prove the hypothesis that lipid apheresis decreases vascular events.

[A telemetrically-guided program for weight reduction in overweight subjects (the SMART study)]. / Telemedizinisch betreutes Programm zur Gewichtsreduktion bei Ubergewichtigen (SMART-Studie).

BACKGROUND AND OBJECTIVE: Compliance with weight reducing programs can be improved by intensive care and control. We tested a telemetrically-guided weight reduction program in overweight and obese persons. PATIENTS AND METHODS: 200 outpatients (62 males) with a mean body mass index of 34 kg/m (2) and a mean age of 47 years participated in a prospective study for one year. During the first six months, telemetrical support (weight-transmission via Bluetooth (short range)-technology, 20-minutes telephone consultation with a nutritionist) was given weekly. After six months, participants were randomly assigned either to a group with further telemonitoring support (telemetric group) or to a group without contact to our clinic (control group). At baseline, and after six and twelve months, body weight, body composition (bioelectrical impedance analysis), and parameters of the metabolic syndrome were assessed at our clinic. RESULTS: 16 participants terminated the study prematurely during the first 6 months and 19 participants (10 from the telemetric group and 9 from the control group) during the second 6 months. According to the intention-to-treat principle, mean weight loss was 6.7 kg (p < 0,001), mean loss of body fat was 5.1 kg (p < 0,001), and mean loss of fat-free mass was 1.6 kg (p < 0,001) within the first six months. Moreover, metabolic and cardiovascular risk markers such as waist circumference, blood pressure, serum triglycerides and blood glucose declined significantly (p < 0,001). Prevalence of the metabolic syndrome fell from 49.5% to 42.0 % (p < 0,05). During the second six months body fat content, waist circumference, and blood glucose increased again in the control group but not in the telemetric group (p < 0,05-0,001). CONCLUSION: The telemetrically-guided weight loss program was a more efficacious measure than the less intensive support without telemonitoring.