Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study.

BACKGROUND: In monarchE, abemaciclib plus endocrine therapy (ET) as adjuvant treatment of hormone receptor-positive, human epidermal growth factor 2-negative, high-risk, early breast cancer (EBC) demonstrated a clinically meaningful improvement in invasive disease-free survival versus ET alone. Detailed safety analyses conducted at a median follow-up of 27 months and key patient-reported outcomes (PROs) are presented. PATIENTS AND METHODS: The safety population included all patients who received at least one dose of study treatment (n = 5591). Safety analyses included incidence, management, and outcomes of common and clinically relevant adverse events (AEs). Patient-reported health-related quality of life, ET symptoms, fatigue, and side-effect burden were assessed. RESULTS: The addition of abemaciclib to ET resulted in higher incidence of grade ≥3 AEs (49.7% versus 16.3% with ET alone), predominantly laboratory cytopenias [e.g. neutropenia (19.6%)] without clinical complications. Abemaciclib-treated patients experienced more serious AEs (15.2% versus 8.8%). Discontinuation of abemaciclib and/or ET due to AEs occurred in 18.5% of patients, mainly due to grade 1/2 AEs (66.8%). AEs were managed with comedications (e.g. antidiarrheals), abemaciclib dose holds (61.7%), and/or dose reductions (43.4%). Diarrhea was generally low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), most were short-lived (≤7 days) and did not recur. Venous thromboembolic events (VTEs) were higher with abemaciclib + ET (2.5%) versus ET (0.6%); in the abemaciclib arm, increased VTE risk was observed with tamoxifen versus aromatase inhibitors (4.3% versus 1.8%). PROs were similar between arms, including being 'bothered by side-effects of treatment', except for diarrhea. At ≥3 months, most patients reporting diarrhea reported 'a little bit' or 'somewhat'. CONCLUSIONS: In patients with high-risk EBC, adjuvant abemaciclib + ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile.

RELAY, ramucirumab plus erlotinib versus placebo plus erlotinib in patients with untreated, EGFR-mutated, metastatic non-small cell lung cancer: Europe/United States subset analysis.

BACKGROUND: In EGFR mutation-positive NSCLC, dual EGFR/VEGFR inhibition compared to EGFR alone increases anti-tumor efficacy. The Phase III RELAY trial demonstrated superior PFS for ramucirumab plus erlotinib (RAM + ERL) over placebo plus erlotinib (PBO + ERL) (HR 0.591 [95% CI 0.461-0.760], p<0.0001). EGFR mutated NSCLC is less prevalent in Western versus Asian patients. This prespecified analysis evaluates efficacy and safety of RAM + ERL in EU and US patients enrolled in RELAY. PATIENTS AND METHODS: Patients were randomized 1:1 to ERL + RAM (10 mg/kg IV) or PBO Q2W. Treatment continued until unacceptable toxicity or progressive disease. Patients were stratified by geographic region (East Asia vs "other" [EU/US and Canada (EU/US)]). Objectives included PFS, ORR, DoR, OS, PFS2, safety and biomarker analysis. RESULTS: EU/US subset included 113/449 (25.9%) patients (58 RAM + ERL, 55 PBO + ERL). RAM + ERL improved PFS (20.6 vs 10.9 months, HR 0.605 [95% CI: 0.362-1.010]). ORR and DCR were similar, but median DoR was longer with RAM + ERL (18.0 vs 10.1 months, HR 0.527 [95% CI: 0.296-0.939]). OS and PFS2 were immature at data cut-off (censoring rates 81.0-81.8% and 67.3-79.3%, respectively). Most commonly reported Grade ≥3 TEAE for RAM + ERL was hypertension (17 [29.8%]) and for PBO + ERL, dermatitis acneiform (5 [9.1%]). CONCLUSION: EU/US subset analysis showed improved efficacy outcomes for RAM + ERL and a safety profile consistent with the overall population. Ramucirumab is a safe and effective addition to standard-of-care EGFR-TKI for EGFR mutation-positive metastatic NSCLC.

Progranulin and chemerin plasma level in obese patients with type 2 diabetes treated with a long-acting insulin analogue and premixed insulin analogue.

Diabetes, referred to as the first non-infectious epidemic, covers a heterogenous group of metabolic diseases marked by hyperglycemia resulting from a defect of insulin secretion and/or insulin resistance. Highly endocrine active adipocytes, particularly those located in white adipose tissue, constitute a source of cytokines, growth factors and complement component as well as adipocytokines including chemerin and progranulin could be the key molecules in the pathomechanism of hypertension, dyslipidemia, metabolic disorders or diabetes type 2. In this study, it was decided to verify the existence of possible relationships between the plasma concentration of progranulin and chemerin and the values of intermediate indices of insulin sensitivity and insulin resistance in patients, both before and after the 6-month insulin therapy by long-acting insulin analogue and premixed insulin analogue. The level of laboratory parameters in blood plasma collected from the control group and from obese individuals with type 2 diabetes mellitus was estimated with the test kits using enzyme-linked immunosorbent assay (ELISA): the test of Mediagnost E103 GmbH GmbH, Reutlingen, Germany for progranulin; the test of BioVendor R&D, Brno, Czech Republic for chemerin. The aim of this study was to assess the progranulin and chemerin plasma level in obese individuals with type 2 diabetes, before and after 6 months of pharmacological treatment with a long-acting analogue human insulin or premixed insulin. In the blood plasma of untreated diabetics - in contrary to progranulin plasma concentration in diabetic patients after management implementation - progranulin was found to occur in a significantly higher concentration in relation to the level of this protein in the blood plasma of control group individuals. Despite the fact that 6-month therapy, both with the insulin mixture and with the long-acting analogue in people with diabetes, does not significantly affect the plasma chemerin concentration, the high, negative correlation between the progranulin and chemerin levels in the blood of individuals of the control group, and a positive one between the levels of progranulin and chemerin in people with diabetes before and after treatment was found. The conducted studies indicated the modified, in the course of diabetes type 2, mutual quantitative relations between progranulin and chemerin - the biological mediators of systemic metabolism, reflecting their active participation in the pathogenetic changes underlying type 2 diabetes. The obtained study results indicate a modification of mutual relationships of the adipocytokines assessed in the paper - progranulin and chemerin, associated with the development of the systemic inflammatory response occurring in the course of obesity which, by inducing insulin resistance, may consequently lead to type 2 diabetes. Taking into consideration the fact that the plasma progranulin and chemerin concentrations in obese patients with type 2 diabetes subjected to pharmacotherapy have not been assessed so far, it is possible that the obtained study results may cast light on the potential influence of the applied treatment on the systemic changes of the both adipocytokines involved in the pathomechanism of the mentioned disorder and thus create the possibility of implementing new therapeutic strategies in the management of patients with diabetes, which is an increasingly common, fast-spreading metabolic disease considered as a non-infectious epidemic of the 21st century.

[Mentoring and workplace-based assessments for final year medical students : An effective way to increase satisfaction and competence?] / Mentoring und arbeitsplatzbasierte Prüfungen im Praktischen Jahr : Ein effektiver Weg zur Steigerung von Zufriedenheit und Kompetenz?

BACKGROUND: The final year of medical training in Germany is one of the least structured and standardized years of medical school. Medical students often complain about a lack of guidance, supervision and feedback. They are mostly asked to perform delegable nonmedical tasks even though student experiences in this period critically determine future decisions for certain medical specialties. Consequently, right from the beginning many young professionals feel overburdened especially by the time pressure of everyday clinical practice. The planned amendment of the medical licensing regulations will make competence-based training even more important. This article therefore aims to examine the extent to which a mentoring-based curriculum with workplace-based examinations during the final year of medical studies can make a valuable contribution to this. METHODS: After a needs assessment (structured literature search, results evaluation and focus groups with both students and medical specialists), a mentoring-based curriculum for final year medical students was developed following the Kern cycle. In 2 work sessions 10 discipline-specific competencies for the fields of anesthesiology, critical care, emergency and pain medicine were established and prioritized, which had to be mastered by every student independently at the end of the training period. Assessment of these competencies was performed on a regular basis by trained mentors in the form of workplace-based assessments (mini-clinical evaluation exercise, mini-CEX, direct observation of procedural skills, DOPS). Multiperspective evaluation was and is the foundation of continuous program development. By September 2019 a total of 40 students had completed the modified curriculum and were subsequently interviewed online about various aspects of the tertial. RESULTS: The response rate to the survey was 80% (n = 32). The gender ratio was balanced (male = 50%, female = 50%). Prioritization and assessment of 10 competencies by trained mentors enabled a focused, demand-driven and high-quality training of final year medical students. Surveyed students found the section mentoring and feedback to be very positive and it supported their learning success (grade 1.5). Despite firmly established feedback structures, in retrospect almost half (51.6%) wanted more structured feedback. Workplace-based assessments were mostly previously unknown (64.6%) but were experienced as helpful and meaningful (76.7%). Students felt confident and prepared for the final state examination (81.3%) and their career start (71.0%) after being part of the program. These findings were accompanied by a high level of satisfaction (grade 1.7) as well as a high recommendation rate for this institution (as a training program for final year medical students and as a career start for residents, both with 93.7%). Thus, the good evaluation results of the department before the start of the project could again be slightly improved. CONCLUSION: A demand-driven, mentoring-based curriculum with integrated workplace-based assessments not only led to high overall student satisfaction but also promoted the quality of teaching in an effective and resource-saving way. Mentoring promotes learning success mainly through feedback and individual learning support and also supports the communicative and social skills of students and mentors alike.

Hepatitis E Is a Rare Finding in Liver Transplant Patients With Chronic Elevated Liver Enzymes and Biopsy-Proven Acute Rejection.

BACKGROUND: In past decades, liver transplant (LT) patients were not routinely screened for hepatitis E virus (HEV) infection, and thus it might have been misdiagnosed as an acute rejection episode. Our aim was to analyze a real-world cohort of LT patients who presented with at least 1 episode of biopsy-proven acute rejection (BPAR) and suffered from persistent elevated transaminases, to evaluate the frequency of HEV infection misdiagnosed as a rejection episode. METHODS: Data from 306 patients transplanted between 1997 and 2017, including 565 liver biopsies, were analyzed. Biopsies from patients suffering from hepatitis C (n = 79; 25.8%) and from patients who presented with a Rejection Activity Index <5 (n = 134; 43.8%) were excluded. A subgroup of 74 patients (with 134 BPAR) with persistently elevated liver enzymes was chosen for further HEV testing. RESULTS: Positive HEV IgG was detectable in 18 of 73 patients (24.7%). Positive HEV RNA was diagnosed in 3 of 73 patients with BPAR (4.1%). Patients with HEV infection showed no difference in etiology of the liver disease, type of immunosuppression, or median Rejection Activity Index. CONCLUSION: Few HEV infections were misdiagnosed as acute rejection episodes in this real-world cohort. Thus, HEV infection is an infrequent diagnosis in cases with persistent elevated liver enzymes and BPAR after LT.

Heart failure among people with Type 2 diabetes mellitus: real-world data of 289 954 people from a diabetes database.

AIM: Comparing people with Type 2 diabetes mellitus with and without heart failure in terms of metabolic control, therapeutic regimen and comorbidities. METHODS: The Prospective Diabetes Registry (DPV) is a longitudinal documentation system for demographics, medical care and outcome in people with diabetes mellitus. It consists of follow-up data from people with diabetes mellitus who have agreed to be recorded in the registry. Clinical data are submitted by general practitioners, specialists and clinics throughout Germany and Austria. Some 289 954 people with Type 2 diabetes mellitus (years 2000 to 2015) were analysed using demographic statistics and adjustment for confounders based on linear and logistic regression analysis. RESULTS: People with Type 2 diabetes mellitus (ICD code: E11) and heart failure (ICD code: I50) (N = 14 723) were older, more often women and presented with longer diabetes duration compared with those without heart failure. After adjustment for age, gender and diabetes duration, people with heart failure showed lower HbA1c , higher BMI and more intense insulin therapy. Analysis revealed that people with heart failure were more often treated with insulin, and more frequently received anti-hypertensives and lipid-lowering medication. They presented with lower systolic and diastolic BP. People with heart failure more frequently showed a history of comorbidities. CONCLUSION: Heart failure is common in diabetes mellitus, but the prevalence in the DPV is lower frequent than expected. The reason for improved metabolic control in heart failure may be intensified therapy with insulin, lipid-lowering medication and anti-hypertensives in this cohort.

[Systemic and local therapy options for sudden sensorineural hearing loss in diabetics]. / Systemische und lokale Hörsturztherapie bei Diabetes mellitus.

Sudden sensorineural hearing loss is not an emergency, but an urgency. Depending on severity, the disease may have a major impact on quality of life. Gold standard in Germany is a systemic, high-dosage glucocorticoid therapy. During oral or intravenous therapy with glucocorticoids, systemic side effects may occur. Especially in diabetics, this therapy may cause acute prominent disorders in glucose metabolism and therefore may be contraindicated. An alternative therapeutic option is intratympanic injection of steroids into the middle ear. Hereby the systemic side effects are absent and only local otologic complications may occasionally occur.

Clinical inertia among patients with type 2 diabetes mellitus treated with DPP-4i and/or SGLT-2i.

OBJECTIVES: Failure to intensify treatment of patients with type 2 diabetes (T2D) in a timely manner is a common challenge. If newer oral anti-diabetic drugs (NOADs) such as dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) do not achieve metabolic control, injectable therapy like insulin or glucagon-like Peptide 1 (GLP-1) receptor agonists are required. We investigated the time in poor glycaemic control (PC, HbA1c > 7%, >7.5%, >8%) in adults with T2D treated with DPP-4i/SGLT-2i until treatment intensification with insulin/GLP-1 or until the most recent documented visit. METHODS: T2D ≥ 18 years were identified from the diabetes patient follow-up registry (DPV), which captures data from diabetes specialist care. Patients with ≥2 documented visits with DPP-4i/SGLT-2i treatment and with the most recent treatment year ≥2015 were included. RESULTS: The study population consisted of 4576 patients treated with DPP-4i/SGLT-2i. A subgroup of 1416 patients were intensified with an injectable therapy. Mean time in PC until intensification with insulin/GLP-1 was 16.7 months (HbA1c > 7%), 15.7 and 15.1 months (HbA1c > 7.5%, HbA1c > 8%) in this subgroup, respectively. Mean time in PC until most recent visit was 12.6, 9.9 and 8.4 months in the subgroup of patients without treatment intensification. CONCLUSIONS: Even with NOADs, a substantial proportion of T2D do not achieve good metabolic control. These findings may be due to individualized target setting for HbA1c, or reluctance of patients and physicians towards injectable therapy. Effective diabetes management strategies are necessary to reduce the risk of adverse outcomes and to increase quality of life in T2D.

Regional frequency variation of revascularization procedures for carotid stenosis in Germany: Secondary data analysis of DRG data from 2012 to 2014.

BACKGROUND: For Germany, regional variation of procedure rates of carotid endarterectomy (CEA) and carotid artery stenting (CAS) performed for carotid stenosis have so far not been analyzed at a national level. The aim of this study was to assess small area estimates of procedure rates among German regions, and to identify regional characteristics, which are associated with the regional frequency of procedures. METHODS: German diagnosis-related groups (DRG) statistics (2012-2014) were analyzed. Inclusion and exclusion criteria for procedural codes were set according to German quality assurance measures in combination with the diagnosis of carotid stenosis (I65.2). Rates of CEA and CAS were indirectly standardized for sex and age. RESULTS: In total, 88,182 procedures were performed (73,042 CEA; 15,367 CAS). The overall procedure rate varied between 13.2 per 100,000 (Augsburg) and 89.2 per 100,000 (Wilhelmshaven). Spatial analysis revealed that regional distribution was significantly clustered. CONCLUSION: The rates of CEA, and especially of CAS showed high regional variation. The spatial distribution was significantly clustered. In addition to the regional prevalence of diabetes mellitus, smoking and obesity, socioeconomic factors, such as income and debts were correlated with the overall frequency of CEA and CAS. No significant association was found between indicators of health infrastructure (e. g. density of hospital beds, vascular surgeons and angiologists) and the overall procedure rate.

[Operative treatment of diabetics with vascular complications : Secondary data analysis of diagnosis-related groups statistics from 2005 to 2014 in Germany]. / Operative Versorgung von Diabetikern mit vaskulären Komplikationen : Sekundärdatenanalyse der DRG-Statistik von 2005 bis 2014 in Deutschland.

BACKGROUND: In Germany approximately 40,000 amputations per year are performed on patients with diabetes mellitus, often with accompanying vascular complications. OBJECTIVE: The aim of this study was to present the various degrees of severity of the vascular complications and the temporal changes of the treatment options in diabetics with vascular complications in Germany. MATERIAL AND METHODS: The microdata of the diagnosis-related groups (DRG) statistics of the Federal Statistical Office were analyzed over the period from 2005 to 2014. All cases were included in which the main or secondary diagnosis of diabetes mellitus with concurrent vascular complications (diabetic angiopathy and peripheral arterial disease) was encrypted. RESULTS: The median age of the 1,811,422 cases was 73 years and 62% were male. While the total number of amputations remained stable over time, there was a 41% reduction in knee-preserving and a 31% reduction in non-knee preserving major amputations with an 18% increase in minor amputations. Revascularization increased by 33% from 36 procedures in 2005 to 48 procedures per 100,000 inhabitants. The increase in revascularization was evident in the area of endovascular therapy alone where there was an increase of 78%. CONCLUSION: Due to the significant increase in endovascular revascularization measures, there was a significant increase in the proportion of diabetes patients with vascular pathologies in whom revascularization was carried out. As a result, improved limb preservation was achieved despite equally high amputation rates due to increasing minor amputation rates.

Pretransplant coronary artery disease is a predictor for myocardial infarction and cardiac death after liver transplantation.

BACKGROUND: Cardiovascular disease is a serious problem of liver transplant (LT) recipients because of increased cardiovascular risk due to immunosuppressive therapy, higher age, intraoperative risk and comorbidities (such as diabetes and nicotine abuse). Reported frequency of cardiovascular events after LT shows a high variability between different LT cohorts. Our aim was to analyze a cohort of LT recipients from a single center in Germany to evaluate frequency of the cardiovascular endpoints (CVE) myocardial infarction and/or cardiac death after LT and to investigate correlations of CVE post LT with pretransplant patient characteristics. PATIENTS: In total, data from 352 LT patients were analyzed. Patients were identified from an administrative transplant database, and all data were retrieved from patients' charts and reports. RESULTS: During the median follow-up of 4.0 (0-13) years, 10 cases of CVE were documented (six myocardial infarctions and four coronary deaths). The frequency of CVE did not differ according to classic cardiovascular risk factors such as body mass index (p=0.071), total cholesterol (p=0.533), hypertension (p=0.747), smoking (p=1.000) and pretransplant diabetes mellitus (p=0.146). In patients with pretransplant coronary heart disease (n=24; 6.8%) CVE were found more frequently (p=0.024). CONCLUSION: In summary, we found a rate of 2.8% CVE after LT in a German transplant cohort. Pretransplant CHD was the only risk factor for CVE, but showed no significant impact on overall survival.

Estimating linkages between forest structural variables and rainfall interception parameters in semi-arid deciduous oak forest stands.

An understanding of the relationship between canopy structure and the water balance is needed for predicting how forest structure changes affect rainfall partitioning and, consequently, water resources. The objective of this study was to predict rainfall interception (I) and canopy storage capacity (S) using canopy structure variables and to investigate how seasonal changes influence their relationship. The study was conducted in twelve 50m×50m plots in the Zagros forest in the western Iranian state of Ilam, protected forests of Dalab region. Average cumulative I was 84.2mm, accounting for 10.2% of cumulative gross precipitation (GP) over a 1-year period. Using a regression based method, S averaged ~1mm and 0.1mm in the leafed and leafless periods, respectively. There were no relationships between tree density and I:GP or S, but I:GP and S increased with leaf area index, canopy cover fraction, basal area, tree height, and diameter at breast height in the leafed period. In addition, wood area index and canopy cover fraction were related to I:GP or S in the leafless period.

Neutralization of mobile antiviral small RNA through peroxisomal import.

In animals, certain viral proteins are targeted to peroxisomes to dampen the antiviral immune response mediated by these organelles1-3. In plants, RNA interference (RNAi) mediated by small interfering (si)RNA is the main antiviral defence mechanism. To protect themselves against the cell- and non-cell autonomous effects of RNAi, viruses produce viral suppressors of RNA silencing (VSR)4, whose study is crucial to properly understand the biological cycle of plant viruses and potentially find new solutions to control these pathogens. By combining biochemical approaches, cell-specific inhibition of RNAi movement and peroxisome isolation, we show here that one such VSR, the peanut clump virus (PCV)-encoded P15, isolates siRNA from the symplasm by delivering them into the peroxisomal matrix. Infection with PCV lacking this ability reveals that piggybacking of these VSR-bound nucleic acids into peroxisomes potentiates viral systemic movement by preventing the spread of antiviral siRNA. Collectively, these results highlight organellar confinement of antiviral molecules as a novel pathogenic strategy that may have its direct counterpart in other plant and animal viruses.

Methods to Assess Autophagy and Chronological Aging in Yeast.

Autophagy is a catabolic process that is crucial for cellular homeostasis and adaptive response to changing environments. Importantly, autophagy has been shown to be induced in many longevity-associated scenarios and to be required to maintain lifespan extension. Notably, autophagy is a highly conserved cellular process among eukaryotes, and the yeast Saccharomyces cerevisiae has become a universal model system for unraveling the molecular machinery underlying autophagic mechanisms. Here, we discuss different protocols to monitor survival and autophagy of yeast cells upon chronological aging. These include the use of propidium iodide to assess the loss of cell membrane integrity, as well as clonogenic assays to directly determine survival rates. Additionally, we describe methods to quantify autophagic flux, including the alkaline phosphatase activity or the GFP liberation assays, which measure the delivery of autophagosomal cargo to the vacuole. In sum, we have recapped established protocols used to evaluate a link between lifespan extension and autophagy in yeast.

[Locoregional solutions for groin defects : Coverage after vascular surgery]. / Lokoregionale Lösungen bei Leistendefekten : Deckung nach gefäßchirurgischen Eingriffen.

INTRODUCTION: Vascular surgery through a groin incision may be associated with severe wound healing disorders in this sensitive area. There are many options to reconstruct the defect surgically. The choice of surgical reconstruction depends mainly on the individual status of vasculature, which is most often compromised in these patients. There are random pattern flaps, as well as perforator, pedicled flaps or microvascular flaps to choose from. AIM: We give an overview of plastic surgical solutions for groin defects, with a special focus on complex wounds after vascular surgical complications. We discuss advantages and disadvantages of different flaps with two case reports and also show alternatives. PATIENTS AND METHODS: We demonstrate in two cases how the reconstruction of the groin defect was planned, taking into account the vascular status, and why we chose an innovative and seldom-used option in each case. RESULTS: The selected flaps, a pedicled fasciocutaneous ALT propeller flap and a perforator-based, pedicled abdominal advancement flap reconstructed the defects successfully. DISCUSSION: The surgical therapy for the reconstruction of groin defects should be chosen according to the individual vascular status to ensure safe and reliable blood supply. To guarantee the best possible reconstruction and avoid postoperative healing disorders and infections, less common flaps should also be considered.

Epidemiological and Molecular Analysis of an Outbreak of Highly Pathogenic Avian Influenza H5N8 clade 2.3.4.4 in a German Zoo: Effective Disease Control with Minimal Culling.

Outbreaks of highly pathogenic avian influenza A virus (HPAIV) subtype H5N8, clade 2.3.4.4, were first reported in January 2014 from South Korea. These viruses spread rapidly to Europe and the North American continent during autumn 2014 and caused, in Germany, five outbreaks in poultry holdings until February 2015. In addition, birds kept in a zoo in north-eastern Germany were affected. Only a few individual white storks (Ciconia ciconia) showed clinical symptoms and eventually died in the course of the infection, although subsequent in-depth diagnostic investigations showed that other birds kept in the same compound of the white storks were acutely positive for or had undergone asymptomatic infection with HPAIV H5N8. An exception from culling all of the 500 remaining zoo birds was granted by the competent authority. Restriction measures included grouping the zoo birds into eight epidemiological units in which 60 birds of each unit tested repeatedly negative for H5N8. Epidemiological and phylogenetical investigations revealed that the most likely source of introduction was direct or indirect contact with infected wild birds as the white storks had access to a small pond frequented by wild mallards and other aquatic wild birds during a period of 10 days in December 2014. Median network analysis showed that the zoo bird viruses segregated into a distinct cluster of clade 2.3.4.4 with closest ties to H5N8 isolates obtained from mute swans (Cygnus olor) in Sweden in April 2015. This case demonstrates that alternatives to culling exist to rescue valuable avifaunistic collections after incursions of HPAIV.

An interdisciplinary review of current and future approaches to improving human-predator relations.

In a world of shrinking habitats and increasing competition for natural resources, potentially dangerous predators bring the challenges of coexisting with wildlife sharply into focus. Through interdisciplinary collaboration among authors trained in the humanities, social sciences, and natural sciences, we reviewed current approaches to mitigating adverse human-predator encounters and devised a vision for future approaches to understanding and mitigating such encounters. Limitations to current approaches to mitigation include too much focus on negative impacts; oversimplified equating of levels of damage with levels of conflict; and unsuccessful technical fixes resulting from failure to engage locals, address hidden costs, or understand cultural (nonscientific) explanations of the causality of attacks. An emerging interdisciplinary literature suggests that to better frame and successfully mitigate negative human-predator relations conservation professionals need to consider dispensing with conflict as the dominant framework for thinking about human-predator encounters; work out what conflicts are really about (they may be human-human conflicts); unravel the historical contexts of particular conflicts; and explore different cultural ways of thinking about animals. The idea of cosmopolitan natures may help conservation professionals think more clearly about human-predator relations in both local and global context. These new perspectives for future research practice include a recommendation for focused interdisciplinary research and the use of new approaches, including human-animal geography, multispecies ethnography, and approaches from the environmental humanities notably environmental history. Managers should think carefully about how they engage with local cultural beliefs about wildlife, work with all parties to agree on what constitutes good evidence, develop processes and methods to mitigate conflicts, and decide how to monitor and evaluate these. Demand for immediate solutions that benefit both conservation and development favors dispute resolution and technical fixes, which obscures important underlying drivers of conflicts. If these drivers are not considered, well-intentioned efforts focused on human-wildlife conflicts will fail.

Relationship between weight change and glycaemic control in patients with type 2 diabetes receiving once-weekly dulaglutide treatment.

AIM: To assess the relationship between weight change and glycated haemoglobin (HbA1c) change in dulaglutide-treated patients by analysing data from six head-to-head phase III AWARD clinical trials. METHODS: At 26 weeks, the relationship between weight and HbA1c was analysed in each trial rather than by pooling data because of differences in design and background therapy. The effect of baseline characteristics was also evaluated with regard to weight and HbA1c response. RESULTS: Across the studies, 87-97% and 83-95% of patients treated with dulaglutide 1.5 and 0.75 mg, respectively, had reductions in HbA1c levels, while 57-88% and 43-84% of patients treated with dulaglutide 1.5 and 0.75 mg, respectively, experienced weight loss. The majority (55-83%) of patients receiving dulaglutide 1.5 mg experienced weight loss and HbA1c reductions, while 41-79% of patients in the dulaglutide 0.75 mg arm lost weight and had reductions in HbA1c level. A weak and inconsistent correlation was observed between the changes in weight and HbA1c (range from -0.223 to 0.267) in patients treated with dulaglutide. The baseline characteristics of gender, age, duration of diabetes, HbA1c, body weight and BMI were not related to different combinations of weight and HbA1c responses. CONCLUSIONS: Dulaglutide is an effective treatment option across the type 2 diabetes treatment spectrum. Dulaglutide showed dose-dependent effects on both weight loss and HbA1c reduction. These effects had a weak correlation and appeared to be independent.

[Indications and results of endovascular therapy of critical limb ischemia]. / Indikationen und Ergebnisse der endovaskulären Therapie der kritischen Extremitätenischämie.

BACKGROUND: Critical limb ischemia (CLI) is the most severe form of peripheral artery occlusive disease and is characterized by high amputation, morbidity and mortality rates. Therefore, revascularization is the essential step in therapy for retention of the affected limb. OBJECTIVES: Although for a long time bypass surgery represented the gold standard in the treatment of CLI, in recent years there has been a disproportionate increase of endovascular treatment despite the lack of level-data. In this review the indications and results of endovascular therapy of CLI are presented on the basis of published data. METHODS: A literature search was carried out to identify publications that compared the results of endovascular and surgical therapy as well as observational studies about different endovascular techniques. RESULTS: The BASIL study provided the highest quality data comparing endovascular and surgical treatment of CLI. The long-term data of the BASIL trial showed that apart from patients with a suitable vein and a life expectancy of more than 2 years, first line endovascular therapy is equivalent to surgical treatment. The equivalence could also be demonstrated in a meta-analysis comparing operative and endovascular treatment of CLI. CONCLUSION: The CLI is a disease with high mortality and morbidity risks. Due to the comparable amputation-free survival times with lower complication rates in the published data, in most patients an endovascular first strategy in experienced centers can be justified.