The potential impact of nanomedicine on COVID-19-induced thrombosis.

Extensive reports of pulmonary embolisms, ischaemic stroke and myocardial infarctions caused by coronavirus disease 2019 (COVID-19), as well as a significantly increased long-term risk of cardiovascular diseases in COVID-19 survivors, have highlighted severe deficiencies in our understanding of thromboinflammation and the need for new therapeutic options. Due to the complexity of the immunothrombosis pathophysiology, the efficacy of treatment with conventional anti-thrombotic medication is questioned. Thrombolytics do appear efficacious, but are hindered by severe bleeding risks, limiting their use. Nanomedicine can have profound impact in this context, protecting delicate (bio)pharmaceuticals from degradation en route and enabling delivery in a targeted and on demand manner. We provide an overview of the most promising nanocarrier systems and design strategies that may be adapted to develop nanomedicine for COVID-19-induced thromboinflammation, including dual-therapeutic approaches with antiviral and immunosuppressants. Resultant targeted and side-effect-free treatment may aid greatly in the fight against the ongoing COVID-19 pandemic.

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells.

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease.

Implementing Home Office Work at a Large Psychiatric University Hospital in Switzerland During the COVID-19 Pandemic: Field Report.

BACKGROUND: During the COVID-19 pandemic in 2020, psychiatric hospitals all over the world had to adapt their services to the prevailing governmental regulations. As a consequence, home office use and telepsychiatry boomed. OBJECTIVE: The purpose of this study was to evaluate the potential of home office use, its adoption, and the association of home office use with employees' mental health in a large psychiatric university hospital in Switzerland. METHODS: We obtained and analyzed home office implementation and use data from the psychiatric university hospital's information technology services. We also conducted a cross-sectional web-based survey to assess the employees' attitudes toward the clinic's crisis management during the COVID-19 pandemic in early 2020. Part of this web-based survey consisted of questions about home office use between March and June 2020, attitudes toward home office implementation, and mental health. Three mental health measures assessed depressive symptoms (Patient Health Questionnaire [PHQ]-2), anxiety (General Anxiety Disorder [GAD]-2), and stress factors (stress module of the PHQ-D); a cut-off score ≥3 was used for the PHQ-2 and GAD-2. RESULTS: Of the 200 participating employees, 69 reported that they had worked from home at least partially (34.5%). Home office use differed significantly across professional groups (χ162=72.72, P≤.001, n=200). Employees experienced neither depressive symptoms (mean 0.76, SD 1.14) nor anxiety (mean 0.70, SD 1.03). The employees reported minor psychosocial stressors (mean 2.83, SD 2.92). The number of reported stress factors varied significantly across groups with different levels of home office use (χ42=9.72, P=.04). CONCLUSIONS: In general, home office implementation appears to be feasible for large psychiatric hospitals, however, it is not equally feasible for all professional groups. Professional groups that require personal contact with patients and technical or manual tasks must work onsite. Further evaluation of home office use in psychiatric hospitals up to the development of clinics that function merely online will follow in future research. The situation created by the COVID-19 pandemic served as a stepping stone to promote home office use and should be used to improve employees' work-life balance, to save employers costs and foster other benefits.

Barotrauma among patients with COVID-19 ARDS versus historical ARDS

RATIONALE Multiple case reports and case series have described pneumothorax and pneumomediastinum as a complication of patients hospitalized with COVID-19, particularly among those receiving invasive mechanical ventilation. However, it is not known whether patients with COVID-19 have a uniquely higher incidence of these events compared to historical ARDS (non-COVID-19 ARDS) patients. METHODS We compared barotrauma rates in patients hospitalized with COVID-19 who received invasive mechanical ventilation between March-July 2020 to patients with non-COVID-19 ARDS who received mechanical ventilation in 2016-2018. We defined barotrauma as pneumothorax or pneumomediastinum during mechanical ventilation. RESULTS We analyzed 222 patients with COVID-19 who received invasive mechanical ventilation and 421 patients with ARDS. Barotrauma events occurred in 13.1% of patients with COVID-19 and 9.3% of historical ARDS patients (p = 0.136). Mean tidal volumes were 5.7 and 6.4 mL/kg of predicted body weight, plateau pressures were 25.6 and 23.6, PEEP was 11.2 and 8.8, and driving pressures were 14.4 and 14.8 cmH2O, respectively, in COVID-19 and non-COVID-19 ARDS. There were 42 pneumothoraces among COVID-19 patients and 50 among historical ARDS patients (p = 0.144). Incidence rates were 1.7 and 2.7 per 100 ventilator days in COVID-19 and historical ARDS respectively (p=0.808). There were 14 cases of pneumomediastinum among patients with COVID-19 compared to 16 among patients with ARDS (p = 0.152). Overall, pneumothoraces were identified within 24 hours of ipsilateral internal jugular or subclavian line placement in 5.4% (5/92) of events. In both groups, barotrauma was associated with fewer vent-free days at 28 days (3.0 vs 9.2 in COVID-19, p < 0.001 and 7.6 vs 11.5 in historical ARDS, p = 0.0214). Barotrauma was not associated with an increased mortality at discharge for either cohort. For COVID-19 patients only, mean plateau pressure and driving pressure were associated with barotrauma events (28 vs 25 cmH2O, p = 0.0015;16.7 vs 14.0 cmH2O, p ≤ 0.01). Administered tidal volume, PEEP, age, sex, tobacco use, obesity, number of comorbidities, and the presence of lung comorbidities were not associated with barotrauma in either cohort. CONCLUSIONS Both COVID-19 and non-COVID-19 ARDS patients who are mechanically ventilated are at high risk of barotrauma;this was not unique to patients with COVID-19. Barotrauma is associated with prolonged ventilation and fewer ventilator-free days. Despite advances in lung-protective ventilation, barotrauma continues to be a significant source of morbidity in patients mechanically ventilated for respiratory failure.

Wie stark trifft die Corona-Pandemie die Kliniken für Orthopädie und Unfallchirurgie?

Die Corona-Pandemie stellt Krankenhäuser vor enorme finanzielle Herausforderungen. Am Beispiel einer Klinik für Orthopädie und Unfallchirurgie soll die Leistungsentwicklung in der stationären Versorgung der ersten 5 Wochen nach Beginn der gesetzgeberisch angeordneten Leistungsreduktion im Vorjahresvergleich sowie eine Bewertung der gesetzgeberisch festgelegten Kompensationsmaßnahmen bewertet werden. Anhand der Leistungszahlen wird ein Vergleich des Zeitraumes 16.03. bis 17.04.2019 und demselben Zeitraum 2020 durchgeführt. Veränderungen von Fallzahl, Casemix, Casemix-Index und Daymix-Index sowie den Belegungstagen werden erfasst. Auf diese Veränderungen werden die monetären Maßnahmen aus dem COVID-19-Krankenhausentlastungsgesetz angewendet und deren Auskömmlichkeit bewertet. Im Vergleich zum Vorjahr kommt es im Beobachtungszeitraum zu einem Rückgang der stationären Aufnahmen von 307 Patienten. Demzufolge waren ein Rückgang des Casemix um 595 Punkte und der Belegungstage um 2320 Tage zu verzeichnen. Es ergibt sich ein Erlösrückgang von ca. 1,9 Mio. EUR. Die Leerbettenpauschale stellt die monetär größte Kompensation der Erlösausfälle dar. Sie beläuft sich auf ca. 1,3 Mio. EUR. Unter Berücksichtigung weiterer Unterstützung und einer Bereinigung um variable Kosten bleibt ein Fehlbetrag von 382.069 € in Bezug auf die stationären Leistungen für 5 Wochen. Die Maßnahmen des Gesetzgebers stellen eine wichtige Stütze zur wirtschaftlichen Absicherung deutscher Krankenhäuser dar. Die fehlende Differenzierung der Maßnahmen nach Fachrichtung führt für Orthopädie und Unfallchirurgie zu einer nur unzureichenden Kompensation.