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Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.Peer Reviewe

Contribution of an Aged Microenvironment to Aging-Associated Myeloproliferative Disease

The molecular and cellular mechanisms of the age-associated increase in the incidence of acute myeloid leukemia (AML) remain poorly understood. Multiple studies support that the bone marrow (BM) microenvironment has an important influence on leukemia progression. Given that the BM niche itself undergoes extensive functional changes during lifetime, we hypothesized that one mechanism for the age-associated increase in leukemia incidence might be that an aged niche promotes leukemia progression. The most frequent genetic alteration in AML is the t(8;21) translocation, resulting in the expression of the AML1-ETO fusion protein. Expression of the fusion protein in hematopoietic cells results in mice in a myeloproliferative disorder. Testing the role of the age of the niche on leukemia progression, we performed both transplantation and in vitro co-culture experiments. Aged animals transplanted with AML1-ETO positive HSCs presented with a significant increase in the frequency of AML-ETO positive early progenitor cells in BM as well as an increased immature myeloid cell load in blood compared to young recipients. These findings suggest that an aged BM microenvironment allows a relative better expansion of pre-leukemic stem and immature myeloid cells and thus imply that the aged microenvironment plays a role in the elevated incidence of age-associated leukemia

Digitalisierte Beratung zur effizienteren Selbstoptimierung: Kritische Anmerkungen zu digitalen Formaten arbeitsbezogener Beratung aus einer Gouvernementalitätsperspektive

"Digital(isiert)e" Beratung verspricht neben Innovation auch Flexibilität, Ubiquität, Globalität, Geschwindigkeit und Legitimität durch evidenzbasierte Wirksamkeit. Für eine sozialwissenschaftlich fundierte arbeitsweltliche Beratung wie Coaching und Supervision ist danach zu fragen, welches Menschen- und Weltbild sich hinter der Digitalisierung verbirgt und welche Anliegen sie transportiert. Dazu wird mit den Theorien Michel Foucaults der gegenwärtige Diskurs auf Steuerungslogiken und Machtverhältnisse hin kritisch analysiert. Dabei zeigt sich, dass die Digitalisierung das "Zeitalter der Gouvernementalität" (Foucault) festigt: Humanistisch geprägte Werte und Ziele wie Reflexion, Anerkennung und Selbsterkenntnis treten in den Hintergrund, während die Nutzbarmachung und Optimierung des Selbst sowie des Beratungsprozesses wichtiger werden: Beratung will und muss effizienzgetrieben ihre Wirksamkeit evidenzbasiert legitimieren, und Digitalisierung erleichtert dies

Efficacy of universal preoperative decolonization with Polyhexanide in primary joint arthroplasty on surgical site infections. A multicenter before-and after-study

Background: Surgical site infections (SSI) are rare but severe complications after total joint arthroplasty (TJA). Decolonization measures prior to elective orthopedic surgeries have shown to reduce the risk of SSI with Staphylococcus aureus (S. aureus). Objective To determine the efficacy of universal decolonization with Polyhexanide on SSI rates with a focus on Staphylococcus aureus in patients with TJA. Methods: Patients scheduled for elective hip or knee TJA in 5 participating certified orthopedic centers were included between 2015 and 2018 into this before and after study. Data on patients, surgeries and infections were prospectively collected. CDC-criteria were used to define and categorize Infections within 90 days after surgery. From January 2017 on, patients received decolonization sets containing Polyhexanide. Patients performed a 5 day decolonization regimen starting 4 days prior to surgery which included wipes, nasal decontamination and oral solution. Results: Thirteen thousand, three hundred fifteen patients received TJA. During intervention 4437 decolonization sets were distributed among 7175 patients. Overall SSI rates increased from 0.68 /100 surgeries to 0.91/ 100 surgeries after implementation of the intervention (IRR 1.32; 95% CI 0.90-1.96). Time series analysis identified an increasing trend of SSI prior to the intervention. After implementation overall SSI rates plateaued. Regression analysis revealed surgery during intervention period to be an independent risk factor for developing a SSI (OR 1.34; 95%CI 1.18-1.53). Initial SSI rates due to S. aureus were 0.24/100 surgeries and decreased to 0.14/100 surgeries (IRR 0.57; 95% CI 0.25-1.22) after introduction of decolonization. Regression analysis revealed surgery during intervention period to be an independent protective factor for developing a SSI with S. aureus (OR 0.57, 95% CI: 0.33-0.99). Overall deep S. aureus SSI decreased significantly from 0.22/100 surgeries to 0.00/100 surgeries in patients adherent to protocol (IRR 0.00, 95% CI 0.00-.85). Conclusion Universal decolonization with Polyhexanide did not reduce overall surgical site infections, but was effective in reducing Staphylococcus aureus - surgical site infections following elective joint arthroplasty. Polyhexanide could extend the list of alternatives to already established decolonization strategies

Model for the influence of an aged microenvironment on leukemia progression.

<p>(<b>A</b>) The standard model describes leukemia development as the clonal evolution of an aberrant clone: a founder cell mutates through multiple subsequent steps, frequently via a chronic phase (CML) to ultimately result in acute myeloid leukemia (AML). The velocity of expansion of the aberrant clone increase along the three phases of leukemia (pre-leukemia, chronic leukemia, acute leukemia). The transitions between the phases are not well described in both cellular and molecular terms, but might be caused by intrinsic/genetic and/or extrinsic changes (figure adapted from ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031523#pone.0031523-Nowell1" target="_blank">[46]</a>). (<b>B</b>) An aged microenvironment increases the velocity of the expansion of an aberrant pre-leukemic clone. The faster expansion of myeloproliferation-initiating stem cells in aged BM thus promoting the leukemic process. In a larger aberrant cell population, the probability of generating additional hits is increased, resulting in a more likely and thus earlier transition to the next phase of leukemia.</p

<i>In vitro</i> culture of AML1-ETO positive stem/progenitor cells on aged and young endosteal cells.

<p>(<b>A</b>) Experimental set-up for isolation of a cell fraction close to the endosteum ( =  endosteal cells) and representative phase contrast images (×10) from adherent endosteal cells from young and aged mice, bar represent 50 µm (<b>B</b>) Experimental set-up for co-culture experiments and FACS analysis for analysis of the Lin−,Sca-1+, c-Kit+ (LSK) cell compartment. (<b>C</b>) Frequency of GFP+ cells among all cells, (<b>D</b>) frequency of GFP+ cells in the LSK population (<b>E</b>) and the total number GFP+LSK cells. n = 3, * = p<0.05. Bars represent the mean ± SEM.</p

Digitalisierte Beratung zur effizienteren Selbstoptimierung : Kritische Anmerkungen zu digitalen Formaten arbeitsbezogener Beratung aus einer Gouvernementalitätsperspektive

»Digital(isiert)e« Beratung verspricht neben Innovation auch Flexibilität, Ubiquität, Globalität, Geschwindigkeit und Legitimität durch evidenzbasierte Wirksamkeit. Für eine sozialwissenschaftlich fundierte arbeitsweltliche Beratung wie Coaching und Supervision ist danach zu fragen, welches Menschen- und Weltbild sich hinter der Digitalisierung verbirgt und welche Anliegen sie transportiert. Dazu wird mit den Theorien Michel Foucaults der gegenwärtige Diskurs auf Steuerungslogiken und Machtverhältnisse hin kritisch analysiert. Dabei zeigt sich, dass die Digitalisierung das »Zeitalter der Gouvernementalität« (Foucault) festigt: Humanistisch geprägte Werte und Ziele wie Reflexion, Anerkennung und Selbsterkenntnis treten in den Hintergrund, während die Nutzbarmachung und Optimierung des Selbst sowie des Beratungsprozesses wichtiger werden: Beratung will und muss effizienzgetrieben ihre Wirksamkeit evidenzbasiert legitimieren, und Digitalisierung erleichtert dies