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Bluttransfusionen ermöglichen es jährlich tausenden von Menschen das Leben zu retten. Allerdings bringt ein unreflektierter Einsatz auch zahlreiche Nachteile mit sich. Patient Blood Management (PBM) beschäftigt sich damit, das optimale Kosten-Nutzen-Verhältnis dieser Maßnahme auszuschöpfen.
Das Programm verfolgt einen multimodalen Ansatz zur Reduktion von Transfusionen. Es zielt darauf ab präoperative Anämie zu erfassen und, wenn möglich, zu therapieren, iatrogenen Blutverlust zu reduzieren und die Anämietoleranz des Körpers maximal auszunutzen. Diese Maßnahmen wurden durch Schulungsprogramme und die Bereitstellung von Informationsmaterial begleitet, um die Sensibilität und das Wissen zu diesem Thema zu vergrößern.
Die vorliegende Arbeit befasst sich mit den Einflüssen der Einführung von PBM auf die Mortalität und Morbidität von Malignompatienten in der Viszeralchirurgie. Die retrospektive Analyse war darauf ausgerichtet, einen Unterschied von 10 % im Zweijahresüberleben vor und nach Einführung festzustellen. Hierfür wurden die Daten von 836 Patienten ausgewertet, die sich über einen Zeitraum von vier Jahren einer onkologischen Operation in der Abteilung für Allgemein- und Viszeralchirurgie der Universitätsklinik Frankfurt am Main unterzogen haben. Davon befanden sich 389 vor und 447 nach der Einführung des Projekts in Behandlung.
Das Ziel der Untersuchung bestand darin, die Sicherheit und den Nutzen von PBM in dieser speziellen Patientengruppe näher zu untersuchen. Dazu wurden der primäre Endpunkt des Zweijahresüberlebens und die sekundären Endpunkte 30-Tages- und 90-Tagesüberleben, Prozentsatz an Patienten mit Anämie, Anzahl der transfundierten Erythrozytenkonzentrate (EK) sowie das Auftreten von Komplikationen nach der Dindo-Clavien Klassifikation festgelegt.
Die erhobenen Daten zeigen ein um 13,1 % (p = < 0,001) verbessertes Überleben nach zwei Jahren in den Vergleichsgruppen vor und nach Einführung des Patient Blood Managements. Es haben 21,5 % (p = < 0,001) weniger Patienten Erythrozytenkonzentrate erhalten, zudem wurde die Gesamtsumme der transfundierten Konzentrate signifikant (p = < 0,001) reduziert.
Dabei kam es zu keinem vermehrten Auftreten von Komplikationen. Dies spricht dafür, dass die Einführung von PBM zur Verbesserung der Patientensicherheit beigetragen hat. Es hat sich gezeigt, dass Patienten ohne oder mit moderaten postoperativen Komplikationen (Dindo-Claven < IIIb) von den Veränderungen im besonderen Maße profitieren.
Eine flächendeckende Implementierung des Konzepts in den klinischen Alltag ist als sicher und empfehlenswert zu betrachten. Neben den Patienten profitiert auch das ärztliche Personal, denn im Rahmen von strukturierten Fortbildungsveranstaltungen wird tiefergehendes Wissen vermittelt und klare Handlungsempfehlungen gegeben. Dies reduziert Unsicherheiten, erhöht die Sensibilität und verringert auf diesem Weg Fehler im Transfusionsmanagement. Des Weiteren ergeben sich ökonomische Vorteile. Durch Schulungen, Anämiescreening und der Anschaffung neuer blutsparender Systeme entstehen zwar zunächst zusätzliche Kosten, allerdings stehen diese Einsparungen, durch einen geringeren EK-Verbrauch sowie geringeren Ausgaben durch eine Senkung der Morbidität, gegenüber.
Es wäre von Interesse, in zukünftigen Untersuchungen die genauen Ursachen für den beobachteten Effekt im verbesserten Langzeitüberleben zu analysieren. Mit diesem Wissen kann eine optimale Nutzung der Einflussfaktoren gewährleistet werden. Zudem sollte es auf dieser Basis möglich werden, das Patientenkollektiv, das von einer Transfusion profitiert, genauer einzugrenzen.
Prediger, Barbara ; Polus, Stephanie ; Mathes, Tim ; Bühn, Stefanie ; Louwen, Frank ; Neugebauer, Edmund ; Pieper, Dawid
Background: The rate of caesarean sections increased in the last decades to about 30% of births in western populations. Many caesarean sections are electively planned without an urgent medical reason for mother or child. Especially in women with a foregoing caesarean section, the procedure is planned early. An early caesarean section though may harm the newborn. Our aim is to evaluate the gestational time point after the 37th gestational week (after prematurity = term) of performing an elective caesarean section with the lowest morbidity for mother and child.
Methods: This is an update of a systematic review previously carried out on behalf of the German Federal Ministry of Health. We will perform a systematic literature search in MEDLINE, EMBASE, CENTRAL and CINAHL. Our primary outcome is the rate of admissions to the neonatal intensive care unit in early versus late term neonates. We will include (quasi) randomized controlled trials and cohort studies. The studies should include pregnant women who have an elective caesarean section at term. We will screen titles and abstracts and the identified full texts of studies for eligibility. Risk of bias will be assessed with the Cochrane Risk of Bias Tool for Randomized Trials or with the Risk of Bias Tool for Non-Randomized Studies of Interventions (ROBINS-I). These tasks will be performed independently by two reviewers. Data will be extracted in beforehand piloted extraction tables. A dose-response meta-analysis will be performed.
Discussion: Our aim is to reach a higher validity in the assessment of the time point of elective caesarean sections by performing a meta-analysis to support recommendations for clinical practice. We assume to identify less randomized controlled trials but a large number of cohort studies analyzing the given question. We will discuss similarities and differences in included studies as well as methodological strengths and weaknesses.
Systematic review registration: PROSPERO CRD42017078231
Steiner, Sabine ; Willfort-Ehringer, Andrea ; Sievert, Horst ; Geist, Volker ; Lichtenberg, Michael ; Del Giudice, Costantino ; Sauguet, Antoine ; Diaz-Cartelle, Juan ; Marx, Claudia ; Ströbel, Armin ; Schult, Ingolf ; Scheinert, Dierk
Objectives: The authors sought to evaluate the performance of the Ranger paclitaxel-coated balloon versus uncoated balloon angioplasty for femoropopliteal lesions at 12 months.
Background: Drug-coated balloons (DCBs) are a promising endovascular treatment option for peripheral artery disease of the femoropopliteal segment, and each unique device requires dedicated clinical study.
Methods: The prospective, randomized RANGER SFA (Comparison of the Ranger™ Paclitaxel-Coated PTA Balloon Catheter and Uncoated PTA Balloons in Femoropopliteal Arteries) study (NCT02013193) enrolled 105 patients with symptomatic lower limb ischemia (Rutherford category 2 to 4) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers. Seventy-one patients (mean age 68 ± 8 years, n = 53 men) were enrolled in the Ranger DCB arm, and 34 patients (mean age 67 ± 9 years, n = 23 men) were assigned to the control group. Twelve-month analysis included patency, safety, and clinical outcomes and quality-of-life assessments.
Results: The DCB group had a greater primary patency rate at 12 months (Kaplan-Meier estimate 86.4% vs. 56.5%), with a significantly longer time to patency failure (log-rank p < 0.001). The estimated freedom from target lesion revascularization rate was 91.2% in the DCB group and 69.9% in the control group at 12 months, with a significantly longer time to reintervention (p = 0.010). No target limb amputations or device-related deaths occurred in either group.
Conclusions: Twelve-month results show that patency was maintained longer after Ranger DCB treatment than after conventional balloon angioplasty, and this result was associated with a low revascularization rate and good clinical outcomes.
Tunaru, Sorin ; Bonnavion, Remy ; Brandenburger, Isabell ; Preussner, Jens ; Thomas, Dominique Jeanette ; Scholich, Klaus ; Offermanns, Stefan
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose. Pharmacological inhibition of 20-HETE formation and blockade of FFAR1 in islets inhibits GSIS. In islets from type-2 diabetic humans and mice, glucose-stimulated 20-HETE formation and 20-HETE-dependent stimulation of GSIS are strongly reduced. We show that 20-HETE is an FFAR1 agonist, which functions as an autocrine positive feed-forward regulator of GSIS, and that a reduced glucose-induced 20-HETE formation contributes to inefficient GSIS in type-2 diabetes.
Epah, Jeremy ; Pálfi, Katalin ; Dienst, Franziska Luise ; Malacarne, Pedro Felipe ; Bremer, Rolf ; Salamon, Michael ; Kumar, Sandeep ; Jo, Hanjoong ; Schürmann, Christoph ; Brandes, Ralf
Rationale: Classic histology is the gold standard for vascular network imaging and analysis. The method however is laborious and prone to artefacts. Here, the suitability of ultramicroscopy (UM) and micro-computed tomography (CT) was studied to establish potential alternatives to histology.
Methods: The vasculature of murine organs (kidney, heart and atherosclerotic carotid arteries) was visualized using conventional 2D microscopy, 3D light sheet ultramicroscopy (UM) and micro-CT. Moreover, spheroid-based human endothelial cell vessel formation in mice was quantified. Fluorescently labeled Isolectin GS-IB4 A647 was used for in vivo labeling of vasculature for UM analysis, and analyses were performed ex vivo after sample preparation. For CT imaging, animals were perfused postmortem with radiopaque contrast agent.
Results: Using UM imaging, 3D vascular network information could be obtained in samples of animals receiving in vivo injection of the fluorescently labeled Isolectin GS-IB4. Resolution was sufficient to measure single endothelial cell integration into capillaries in the spheroid-based matrigel plug assay. Because of the selective staining of the endothelium, imaging of larger vessels yielded less favorable results. Using micro-CT or even nano-CT, imaging of capillaries was impossible due to insufficient X-ray absorption and thus insufficient signal-to-noise ratio. Identification of lumen in murine arteries using micro-CT was in contrast superior to UM.
Conclusion: UM and micro-CT are two complementary techniques. Whereas UM is ideal for imaging and especially quantifying capillary networks and arterioles, larger vascular structures are easier and faster to quantify and visualize using micro-CT. 3D information of both techniques is superior to 2D histology. UM and micro-CT together may open a new field of clinical pathology diagnosis.
Tran, Bach Xuan ; Pham, Thang Van ; Ha, Giang Hai ; Ngo, Anh Toan ; Nguyen, Long Hoang ; Vu, Thuc Thi Minh ; Do, Ha Ngoc ; Nguyen, Vu ; Nguyen, Anh Tuan Le ; Tran, Tung Thanh ; Truong, Nu Thi ; Hoang, Vuong Quan ; Ho, Tung Manh ; Dam, Nhue Van ; Vuong, Thu Trang ; Nguyen, Hung Quang ; Le, Huong Thi ; Do, Hoa Thi ; Moir, Mackenzie ; Shimpuku, Yoko ; Dhimal, Meghnath ; Arya, Shalini Subash ; Nguyen, Tu Huu ; Bhattarai, Suraj ; Latkin, Carl A. ; Ho, Cyrus S. H. ; Ho, Roger C. M.
Child maltreatment remains a major health threat globally that requires the understanding of socioeconomic and cultural contexts to craft effective interventions. However, little is known about research agendas globally and the development of knowledge-producing networks in this field of study. This study aims to explore the bibliometric overview on child maltreatment publications to understand their growth from 1916 to 2018. Data from the Web of Science Core Collection were collected in May 2018. Only research articles and reviews written in the English language were included, with no restrictions by publication date. We analyzed publication years, number of papers, journals, authors, keywords and countries, and presented the countries collaboration and co-occurrence keywords analysis. From 1916 to 2018, 47,090 papers (53.0% in 2010–2018) were published in 9442 journals. Child Abuse & Neglect (2576 papers; 5.5%); Children and Youth Services Review (1130 papers; 2.4%) and Pediatrics (793 papers, 1.7%) published the most papers. The most common research areas were Psychology (16,049 papers, 34.1%), Family Studies (8225 papers, 17.5%), and Social Work (7367 papers, 15.6%). Among 192 countries with research publications, the most prolific countries were the United States (26,367 papers), England (4676 papers), Canada (3282 papers) and Australia (2664 papers). We identified 17 authors who had more than 60 scientific items. The most cited papers (with at least 600 citations) were published in 29 journals, headed by the Journal of the American Medical Association (JAMA) (7 papers) and the Lancet (5 papers). This overview of global research in child maltreatment indicated an increasing trend in this topic, with the world’s leading centers located in the Western countries led by the United States. We called for interdisciplinary research approaches to evaluating and intervening on child maltreatment, with a focus on low-middle income countries (LMICs) settings and specific contexts.
Hasson, Uri ; Iacovacci, Jacopo ; Davis, Ben ; Flanagan, Ryan ; Tagliazucchi, Enzo ; Laufs, Helmut ; Lacasa, Lucas
We explore a combinatorial framework which efficiently quantifies the asymmetries between minima and maxima in local fluctuations of time series. We first showcase its performance by applying it to a battery of synthetic cases. We find rigorous results on some canonical dynamical models (stochastic processes with and without correlations, chaotic processes) complemented by extensive numerical simulations for a range of processes which indicate that the methodology correctly distinguishes different complex dynamics and outperforms state of the art metrics in several cases. Subsequently, we apply this methodology to real-world problems emerging across several disciplines including cases in neurobiology, finance and climate science. We conclude that differences between the statistics of local maxima and local minima in time series are highly informative of the complex underlying dynamics and a graph-theoretic extraction procedure allows to use these features for statistical learning purposes.
Brinker, Titus Josef ; Alfitian, Jonas ; Seeger, Werner ; Groneberg, Jan David Alexander ; Kalle, Christof von ; Enk, Alexander ; Herth, Felix ; Kreuter, Michael ; Bauer, Claudia M. ; Gatzka, Martina ; Suhre, Janina Leonie
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a "selfie" altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app "Smokerface" (=mixed − methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18–40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2–3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students
Hommers, Leif ; Richter, Jan ; Yang, Yunbo ; Raab, Annette ; Baumann, Christian ; Lang, Konstantin ; Schiele, Miriam A. ; Weber, Heike ; Wittmann, André ; Wolf, Christiane ; Alpers, Georg W. ; Arolt, Volker ; Domschke, Katharina ; Fehm, Lydia ; Fydrich, Thomas ; Gerlach, Alexander ; Gloster, Andrew T. ; Hamm, Alfons ; Helbig-Lang, Sylvia ; Kircher, Tilo ; Lang, Thomas ; Pané-Farré, Christiane A. ; Pauli, Paul ; Pfleiderer, Bettina ; Reif, Andreas ; Romanos, Marcel ; Straube, Benjamin ; Ströhle, Andreas ; Wittchen, Hans-Ulrich ; Frantz, Stefan ; Ertl, Georg ; Lohse, Martin ; Lüken, Ulrike ; Deckert, Jürgen
Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.