Results from Canton Grisons of Switzerland suggest repetitive testing reduces SARS-CoV-2 incidence (February-March 2021).

In February 2021, in response to emergence of more transmissible SARS-CoV-2 virus variants, the Canton Grisons launched a unique RNA mass testing program targeting the labour force in local businesses. Employees were offered weekly tests free of charge and on a voluntary basis. If tested positive, they were required to self-isolate for ten days and their contacts were subjected to daily testing at work. Thereby, the quarantine of contact persons could be waved.Here, we evaluate the effects of the testing program on the tested cohorts. We examined 121,364 test results from 27,514 participants during February-March 2021. By distinguishing different cohorts of employees, we observe a noticeable decrease in the test positivity rate and a statistically significant reduction in the associated incidence rate over the considered period. The reduction in the latter ranges between 18 and 50%. The variability is partly explained by different exposures to exogenous infection sources (e.g., contacts with visiting tourists or cross-border commuters). Our analysis provides the first empirical evidence that applying repetitive mass testing to a real population over an extended period of time can prevent spread of COVID-19 pandemic. However, to overcome logistic, uptake, and adherence challenges it is important that the program is carefully designed and that disease incursion from the population outside of the program is considered and controlled.

Delayed inhibition of agonist-induced granulocyte-platelet aggregation after low-dose sevoflurane inhalation in humans.

BACKGROUND: Sevoflurane can be used as sedative-analgesic drug with endothelial protective properties. We tested whether low-dose sevoflurane inhalation provides sustained inhibition of detrimental granulocyte-platelet aggregation in humans. METHODS: Ten healthy male volunteers were enrolled in this crossover study. Each subject inhaled sevoflurane for 1 h at 0.5-1 vol % end-tidal concentration in oxygen (50 vol %). Inhaling oxygen (50 vol %) alone served as control. Venous blood samples were collected at baseline before inhalation, immediately after inhalation, and 24 h thereafter, and were used for flow cytometry to determine platelet surface marker (CD41, CD42b, CD62P/P-selectin, and PAC-1) on platelets and granulocytes and for kaolin-induced clot formation, as assessed by thromboelastography. In flow cytometry experiments, platelets were stimulated with arachidonic acid (AA, 30 microM), adenosine diphosphate (ADP, 1 microM), and thrombin receptor agonist peptide-6 (TRAP-6, 6 microM). RESULTS: AA, ADP, and TRAP-6 markedly increased the expression of CD62P on platelets, whereas CD42b (shedding) and PAC-1 (heterotypic conjugates) expression decreased. The amount of granulocyte-platelet aggregates increased upon agonist stimulation. Low-dose sevoflurane inhalation reduced ADP-induced CD62P expression on platelets 24 h after inhalation, and inhibited the formation of granulocyte-platelet aggregates under stimulation with AA and ADP after 1 and 24 h, and with TRAP-6 after 24 h compared with control. Inhibition of granulocyte-platelet aggregates was accompanied by reduced clot firmness 24 h after sevoflurane inhalation compared with control. CONCLUSIONS: We demonstrated for the first time that inhaling low-dose sevoflurane (<1 vol % end-tidal) inhibits agonist-induced granulocyte-platelet interactions 24 h after administration and thus counteracts thromboinflammatory processes.

Preconditioning by isoflurane retains its protection against ischemia-reperfusion injury in postinfarct remodeled rat hearts.

BACKGROUND: Postinfarct remodeling in the heart may affect protective signaling. We tested whether isoflurane preconditioning retains its protection in postinfarct remodeled hearts. METHODS: Myocardial remodeling was induced by ligation of the left anterior descending coronary artery in male Wistar rats. Six weeks later, diseased hearts were mounted on a Langendorff apparatus and exposed to 40 min of ischemia followed by 90 min of reperfusion. Isoflurane preconditioning was induced with 1.5 MAC (2.1 vol%) isoflurane for 15 min. Infarct size was determined using 1% triphenyltetrazolium chloride staining and corroborated with measurements of lactate dehydrogenase (LDH) release into the perfusate. In some experiments, the protein kinase B and mitochondrial ATP-dependent potassium channel inhibitors LY294002 (10 microM) or 5-hydroxydecanoate (100 microM), respectively, were concomitantly added with isoflurane. Cardiac function was recorded. RESULTS: Six weeks after permanent coronary artery ligation, infarct rats exhibited a markedly increased heart weight/body weight index (5.41 +/- 0.64 vs 3.60 +/- 0.59 g/kg, P < 0.0001) confirming remodeling with compensatory hypertrophy. Isoflurane preconditioning decreased LDH release and reduced infarct size from 32% +/- 6% to 2% +/- 2% (P < 0.0001). Concomitant administration of LY294002 or 5-hydroxydecanoate with isoflurane completely abolished this protection. Functional assessment also showed significant protection from postischemic stunning by isoflurane preconditioning in remodeled hearts, which was lost in the presence of both blockers. CONCLUSIONS: Myocardial preconditioning with isoflurane retains its protection against ischemia/reperfusion injury in postinfarct remodeled rat hearts via similar signaling pathways, as previously reported in healthy hearts.

Pulmonary aspiration: new therapeutic approaches in the experimental model.

BACKGROUND: Acute lung injury caused by gastric aspiration is a frequent occurrence in unconscious patients. Acute respiratory distress syndrome in association with gastric aspiration carries a mortality of up to 30% and accounts for up to 20% of deaths associated with anesthesia. Although the clinical condition is well known, knowledge about the exact inflammatory mechanisms is still incomplete. This study was performed to define the role of alveolar macrophages in this inflammatory response. In addition, potentially modifying effects of intratracheally applied nuclear factor kappaB inhibitor pyrrolidine dithiocarbamate were investigated. METHODS: Rat alveolar macrophages were depleted by intratracheal administration of clodronate liposomes, and lung injury was evaluated 6 h after instillation of 0.1N hydrochloric acid. In a second set of experiments, pyrrolidine dithiocarbamate was intratracheally instilled 3 h after hydrochloric acid application, and injury parameters were determined. RESULTS: Depletion of alveolar macrophages resulted in decreased production of inflammatory mediators in acid aspiration (23-80% reduction of messenger RNA or protein of inflammatory mediators; P < 0.05) and consequently also in diminished neutrophil recruitment (36% fewer neutrophils; P < 0.01). Treatment with pyrrolidine dithiocarbamate was highly effective in decreasing neutrophil recruitment (66%; P < 0.01) and vascular permeability (80%; P < 0.001). CONCLUSIONS: These data suggest that alveolar macrophages play an essential role in the inflammatory response of acid-induced lung injury. For the first time, attenuation of acid-induced lung injury with an inhibitor, applied after the onset of injury, is shown.