Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study

BACKGROUND Progranulin is a widely expressed pleiotropic growth factor with a central regulatory effect during the early immune response in sepsis. Progranulin signaling has not been systematically studied and compared between sepsis, community-acquired pneumonia (CAP), COVID-19 pneumonia and a sterile systemic inflammatory response (SIRS). We delineated molecular networks of progranulin signaling by next-generation sequencing (NGS), determined progranulin plasma concentrations and quantified the diagnostic performance of progranulin to differentiate between the above-mentioned disorders using the established biomarkers procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) for comparison. METHODS The diagnostic performance of progranulin was operationalized by calculating AUC and ROC statistics for progranulin and established biomarkers in 241 patients with sepsis, 182 patients with SIRS, 53 patients with CAP, 22 patients with COVID-19 pneumonia and 53 healthy volunteers. miRNAs and mRNAs in blood cells from sepsis patients (n = 7) were characterized by NGS and validated by RT-qPCR in an independent cohort (n = 39) to identify canonical gene networks associated with upregulated progranulin at sepsis onset. RESULTS Plasma concentrations of progranulin (ELISA) in patients with sepsis were 57.5 (42.8-84.9, Q25-Q75) ng/ml and significantly higher than in CAP (38.0, 33.5-41.0~ng/ml, p < 0.001), SIRS (29.0, 25.0-35.0~ng/ml, p < 0.001) and the healthy state (28.7, 25.5-31.7~ng/ml, p < 0.001). Patients with COVID-19 had significantly higher progranulin concentrations than patients with CAP (67.6, 56.6-96.0 vs. 38.0, 33.5-41.0~ng/ml, p < 0.001). The diagnostic performance of progranulin for the differentiation between sepsis vs. SIRS (n = 423) was comparable to that of procalcitonin. AUC was 0.90 (95% CI = 0.87-0.93) for progranulin and 0.92 (CI = 0.88-0.96, p = 0.323) for procalcitonin. Progranulin showed high discriminative power to differentiate bacterial CAP from COVID-19 (sensitivity 0.91, specificity 0.94, AUC 0.91 (CI = 0.8-1.0) and performed significantly better than PCT, IL-6 and CRP. NGS and partial RT-qPCR confirmation revealed a transcriptomic network of immune cells with upregulated progranulin and sortilin transcripts as well as toll-like-receptor 4 and tumor-protein 53, regulated by miR-16 and others. CONCLUSIONS Progranulin signaling is elevated during the early antimicrobial response in sepsis and differs significantly between sepsis, CAP, COVID-19 and SIRS. This suggests that progranulin may serve as a novel indicator for the differentiation between these disorders. TRIAL REGISTRATION Clinicaltrials.gov registration number NCT03280576 Registered November 19, 2015

Stages of parental engagement in a universal parent training program

This paper reports findings on parental engagement in a community-based parent training intervention. As part of a randomized trial, 821 parents were offered group-based Triple P as a parenting skills prevention program. Program implementation was conducted by practitioners. The intervention was implemented between Waves 1 and 2 of a longitudinal study, with a participation rate of 69% and a retention rate of 96%. The study finds that a practitioner-led dissemination can achieve recruitment and completion rates that are similar to those reported in researcher-led trials. Second, the study found that different factors are associated with the various stages of the parental engagement process. Family-related organizational and timing obstacles to participation primarily influence the initial stages of parental involvement. The strength of neighborhood networks plays a considerable role at the participation and completion stages of parental engagement. The general course climate and the intensity of program exposure predict the utilization of the program several months after the delivery

Planspiel "Telemedizin" - Didaktik ermöglicht gelebte Erfahrungen mit integrierter Versorgung

Das Modul „Gesellschaft und Versorgungssysteme der Zukunft“ ist im 6. Semester des Bachelorstudiums Ergotherapie an der ZHAW (Züricher Hochschule für angewandte Wissenschaften) angesiedelt und thematisiert die Wechselwirkungen zwischen gesellschaftlichem Wandel, integrativen Versorgungsnetzen und Ergotherapie. Didaktische Überlegungen führten zur Neuentwicklung des Planspiels (engl. policy game or serious game) „Telemedizin“, das systemisch Chancen und Risiken des Einbezugs von telemedizinischen Leistungen im Gesundheitswesen thematisiert. Durch ein konsequent umgesetztes Skill Konzept im Studium sind die Studierenden gewöhnt, Rollen adäquat einzunehmen. Darauf aufbauend erhalten die Studierenden im Planspiel einen Einblick in die unterschiedlichen Perspektiven von Betroffenen und Akteuren im Gesundheits- und Sozialwesen und erfahren, wie sich die voneinander abhängigen Akteure systemisch beeinflussen