Literatur-Rundschau

Hans Hafenbrack: Geschichte des Evangelischen Pressedienstes. Evangelische Pressearbeit von 1848 bis 1981 (Michael Schmolke)Matthias Kohring: Vertrauen in Journalismus (Heinz Niederleitner)Romy Fröhlich/Christina Holtz-Bacha (Hg.): Journalism Education in Europe and North America (Michael Hamischmacher)Monika Boll: Nachtprogramm. Intellekte Gründungsdebattenin der frühen Bundesrepublik (Verena Blaum)Walter van Rossum: Meine Sonntage mit "Sabine Christiansen". Wie das Palaver uns regiert (Ute Stenert)Vera Bücker: Nikolaus Groß. Politischer Journalist und Katholik im Widerstand des Kölner Kreises (Matthias Kopp)Elisabeth Hurth: "Alle Toten auf die Plätze!" Die mediale Inszenierung des Todes (Helmuth Rolfes)Luc Jochimsen: Dieses Jahr in Jerusalem. Theodor Herzl - Traum und Wirklichkeit (Elisabeth Harant)Theodor Herzl: Die treibende Kraft. Feuilletons (Elisabeth Harant)Ulrike Röttger (Hg.): Theorien der Public Relations. Grundlagen und Perspektiven der PR-Forschung (Lars Rademacher)

Ruxolitinib for the treatment of SARS-CoV-2 induced acute respiratory distress syndrome (ARDS)

To establish novel and effective treatment combinations for chronic myelomonocytic leukemia (CMML) preclinically, we hypothesized that supplementation of CMML cells with the human oncogene Meningioma 1 (MN1) promotes expansion and serial transplantability in mice, while maintaining the functional dependencies of these cells on their original genetic profile. Using lentiviral expression of MN1 for oncogenic supplementation and transplanting transduced primary mononuclear CMML cells into immunocompromised mice, we established three serially transplantable CMML-PDX models with disease-related gene mutations that recapitulate the disease in vivo. Ectopic MN1 expression was confirmed to enhance the proliferation of CMML cells, which otherwise did not engraft upon secondary transplantation. Furthermore, MN1-supplemented CMML cells were serially transplantable into recipient mice up to 5 generations. This robust engraftment enabled an in vivo RNA interference screening targeting CMML-related mutated genes including NRAS, confirming that their functional relevance is preserved in the presence of MN1. The novel combination treatment with azacitidine and the MEK-inhibitor trametinib additively inhibited ERK-phosphorylation and thus depleted the signal from mutated NRAS. The combination treatment significantly prolonged survival of CMML mice compared to single-agent treatment. Thus, we identified the combination of azacitidine and trametinib as an effective treatment in NRAS-mutated CMML and propose its clinical development

The janus-kinase inhibitor ruxolitinib in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 (coronavirus disease 2019), which is associated with high morbidity and mortality, especially in elder patients. Acute respiratory distress syndrome (ARDS) is a life-threatening complication of COVID-19 and has been linked with severe hyperinflammation. Dexamethasone has emerged as standard of care for COVID-19 associated respiratory failure. In a non-randomized prospective phase II multi-center study, we asked whether targeted inhibition of Janus kinase-mediated cytokine signaling using ruxolitinib is feasible and efficacious in SARS-CoV-2- induced ARDS with hyperinflammation. Sixteen SARS-CoV-2 infected patients requiring invasive mechanical ventilation for ARDS were treated with ruxolitinib in addition to standard treatment. Ruxolitinib treatment was well tolerated and 13 patients survived at least the first 28 days on treatment, which was the primary endpoint of the trial. Immediate start of ruxolitinib after deterioration was associated with improved outcome, as was a lymphocyte-to-neutrophils ratio above 0.07. Together, treatment with the janus-kinase inhibitor ruxolitinib is feasible and might be efficacious in COVID-19 induced ARDS patients requiring invasive mechanical ventilation. The trial has been registered under EudraCT-No.: 2020-001732-10 and NCT04359290

Treat-to-target strategies for the management of familial Mediterranean Fever in children

Abstract Background The objective of this initiative was to develop a treat-to-target (T2T) approach for the management of patients with Familial Mediterranean Fever (FMF), including the definition of a complex treatment target, and establish strategies that improve patient care and long-term outcome. Methods An initial set of statements as well as a flow chart visualising the proposed concept was developed. To adapt the preliminary statements to the current state of knowledge, a systematic literature search was performed and the modified statements were subject to a Delphi approach. To ensure the applicability of the statements in daily practice, an online survey was conducted among paediatric rheumatologists in Germany. In addition, data from the national AID-NET registry were analysed with respect to therapeutic response. Results This T2T initiative yielded a total of 26 statements guiding FMF management with respect to diagnosis, treatment targets, treatment strategies and monitoring. The online survey identified cut-off values for inflammatory markers indicating treatment intensification and appropriate measures in case of colchicine intolerance or non-adherence. The analysis of data derived from the national AID-NET showed that colchicine therapy was successfully terminated in 61% of patients (27 out of 44) with heterozygous MEFV mutations. Multidimensional treatment targets incorporating objective and subjective reported outcome measures were developed. These provide the basis for stratifying patients into the following treatment paths: continue colchicine, persisting attacks / inflammation, colchicine intolerance, persisting arthritis, colchicine reduction and adjustment/reduction of biologics. Conclusions The proposed consensus treatment plan for the management of FMF incorporates multidimensional targets allowing transparent treatment decisions, which will promote personalised disease management and increase adherence to therapy

COVID-19 Induced Acute Respiratory Distress Syndrome — A Multicenter Observational Study

Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients