Dooring-Fahrradunfälle mit schweren Verletzungsmustern: 10-Jahres-Studie eines Level-1-Traumazentrums

Dooring Bicycle Accidents with Severe Injury Patterns: 10-Year Study of a Level 1 Trauma Cente

Climate data, localisation of the sting, grade of anaphylaxis and therapy of hymenoptera stings.

International epidemiological studies indicate that around 1-7% of the population respond with an allergic reaction to a hymenoptera sting, which is frequently associated with admission to an emergency department. This retrospective study included patients admitted between 2009 and 2013 to an emergency department after a hymenoptera sting. In all, 86 (60.1%) men and 57 (39.9%) women were included in the study. The mean age was 43 years, with a range from 19 to 84 years. The most common localisations of a sting were the head (n = 33; 22.5%), the hands (n = 32; 21.9%) and the arms (n = 26; 17.8%). In women, we recorded significantly more stings in distal extremities (p = 0.033) and in men stings in the rump and head were most frequent. Local swellings were observed in 67.1% (n = 96) of patients and 34.3% (n = 49) patients exhibited an anaphylactic reaction. Of these, 21.7% (n = 31) suffered from a grade I, 6.3% (n = 9) grade II, 4.2% (n = 6) grade III and 2.1% (n = 3) grade IV anaphylactic reactions. 46% (66) of the patients were given antihistamines, 45% (64) intravenous glucocorticoids and only 12.5% (16) epinephrine. Most stings were recorded on days without rainfall (p = 0.013), with more hours of sunshine (p = 0.001), low relative humidity (p = 0.006), with mean air pressure above 954.3 hPa and on days with mean temperature above 24.2 °C (p = 0.001). In conclusion, the most hymenoptera stings induced local swelling only; severe reactions were rare. The most dangerous stings are enoral and result from inattentive drinking. Epinephrine was rarely used in anaphylactic reactions

The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma-Association with Clinical Outcome and Tumor Phenotypes

In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter-and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma

Cardioneuroablation: Catheter Vagal Denervation as a New Therapy for Cardioinhibitory Syncope

The vasovagal syncope is the most frequent cause of transient loss of consciousness, especially in young people without significant heart disease. The malignant cardioinhibitory form is caused by abrupt and intense vagal reflex with or without defined triggers. Refractory cases to preventive measures and pharmacological handling has been treated with definitive pacemaker implantation. Besides showing questionable results, pacemaker implantation is highly rejected by young patients. In the late 1990s, we proposed specific vagal denervation by catheter ablation and spectral mapping, for paroxysmal AF, functional bradyarrhythmias and severe cases of malignant cardioinhibitory syncope giving rise to cardioneuroablation. Recently, many authors worldwide have been reproducing the cardioneuroablation results where elimination or significant reduction of the vagal response were observed, which abolished symptoms in more than 75% of patients followed up to 14 years, without complications. Therefore, cardioneuroablation has shown to be a real therapeutic option in malignant syncope cardioinhibitory and in any exclusive vagal mediated bradyarrhythmia without the need for pacemaker implantation

Prevention of Esophageal Damage During Ablation of Atrial Fibrillation by the Esophagus Mechanical Deviation

Atrial fibrillation is the most prevalent arrhythmia in the world population. Despite the use of antiarrhythmics, it is difficult to control clinically, causing symptoms and mainly generating risk of a thromboembolic event. Since 1998, by means of radiofrequency ablation, the treatment of atrial fibrillation has completely changed, but together with this important evolution complications from this ablative treatment technique have also started. In addition to the pulmonary vein stenosis caused by the ablation and later corrected with the change in the technique, atrioesophageal fistulas appeared due to the application of radiofrequency in the posterior wall of the left atrium. This wall is very close (0.5 cm onaverage) to the esophagus, which facilitates the formation of the fistula that leads to the death of almost 100% of the affected patients, despite the various treatment measurements already developed. To avoid this serious complication, several authors have created techniques to protect the esophagus including its mechanical deviation to a region opposite to the radiofrequency application, taking advantage of its mobility and easiness of handling. The mechanical deviation of the esophagus has proven to be the simplest, cheapest and most efficient way to protect this organ from radiofrequency thermal damage during atrial fibrillation ablation

Prevention of Esophageal Damage During Ablation of Atrial Fibrillation by the Esophagus Mechanical Deviation

Atrial fibrillation is the most prevalent arrhythmia in the world population. Despite the use of antiarrhythmics, it is difficult to control clinically, causing symptoms and mainly generating risk of a thromboembolic event. Since 1998, by means of radiofrequency ablation, the treatment of atrial fibrillation has completely changed, but together with this important evolution complications from this ablative treatment technique have also started. In addition to the pulmonary vein stenosis caused by the ablation and later corrected with the change in the technique, atrioesophageal fistulas appeared due to the application of radiofrequency in the posterior wall of the left atrium. This wall is very close (0.5 cm onaverage) to the esophagus, which facilitates the formation of the fistula that leads to the death of almost 100% of the affected patients, despite the various treatment measurements already developed. To avoid this serious complication, several authors have created techniques to protect the esophagus including its mechanical deviation to a region opposite to the radiofrequency application, taking advantage of its mobility and easiness of handling. The mechanical deviation of the esophagus has proven to be the simplest, cheapest and most efficient way to protect this organ from radiofrequency thermal damage during atrial fibrillation ablation

The Human Melanoma Proteome Atlas—Complementing the melanoma transcriptome

The MM500 meta‐study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass‐spectrometry‐based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well‐annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein‐coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease

Bridging the gap: a celebratiom of humanity: a photo project by Christian Tasso = Acortando distancias: una celebración de la humanidad: un proyecto fotográfico de Christian Tasso

Resumen: La necesidad de garantizar la plena inclusión y participación de las personas con discapacidad en la sociedad empujó a la Unión Europea a poner en marcha Bridging the Gap, un proyecto gestionado por un consorcio de agencias de cooperación europeas y organizaciones de personas con discapacidad que FIIAPP tiene el privilegio de liderar. Trabajar en países de África y América Latina con este objetivo nos ha permitido aprender mucho, fortalecer y ampliar nuestro compromiso con el desarrollo inclusivo, e incorporar un objetivo no siempre presente en la acción para el desarrollo

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline