Infection control measures to prevent outbreaks of COVID-19 in Quebec hemodialysis units: a cross-sectional survey.

BACKGROUND: Limited space and resources are potential obstacles to infection prevention and control (IPAC) measures in in-centre hemodialysis units. We aimed to assess IPAC measures implemented in Quebec's hemodialysis units during the spring of 2020, describe the characteristics of these units and document the cumulative infection rates during the first year of the COVID-19 pandemic. METHODS: For this cross-sectional survey, we invited leaders from 54 hemodialysis units in Quebec to report information on the physical characteristics of the unit and their perceptions of crowdedness, which IPAC measures were implemented from Mar. 1 to June 30, 2020, and adherence to and feasibility of appropriate IPAC measures. Participating units were contacted again in March 2021 to collect information on the number of COVID-19 cases in order to derive the cumulative infection rate of each unit. RESULTS: Data were obtained from 38 of the 54 units contacted (70% response rate), which provided care to 4485 patients at the time of survey completion. Fourteen units (37%) had implemented appropriate IPAC measures by 3 weeks after Mar. 1, and all 38 units had implemented them by 6 weeks after. One-third of units were perceived as crowded. General measures, masks and screening questionnaires were used in more than 80% of units, and various distancing measures in 55%-71%; reduction in dialysis frequency was rare. Data on cumulative infection rates were obtained from 27 units providing care to 4227 patients. The cumulative infection rate varied from 0% to 50% (median 11.3%, interquartile range 5.2%-20.2%) and was higher than the reported cumulative infection rate in the corresponding region in 23 (85%) of the 27 units. INTERPRETATION: Rates of COVID-19 infection among hemodialysis recipients in Quebec were elevated compared to the general population during the first year of the pandemic, and although hemodialysis units throughout the province implemented appropriate IPAC measures rapidly in the spring of 2020, many units were crowded and could not maintain physical distancing. Future hemodialysis units should be designed to minimize airborne and droplet transmission of infection.

Statins Reduce Thoracic Aortic Aneurysm Growth in Marfan Syndrome Mice via Inhibition of the Ras-Induced ERK (Extracellular Signal-Regulated Kinase) Signaling Pathway.

Background Statins reduce aneurysm growth in mouse models of Marfan syndrome, although the mechanism is unknown. In addition to reducing cholesterol, statins block farnesylation and geranylgeranylation, which participate in membrane-bound G-protein signaling, including Ras. We dissected the prenylation pathway to define the effect of statins on aneurysm reduction. Methods and Results Fbn1C1039G/+ mice were treated with (1) pravastatin (HMG-CoA [3-hydroxy-3-methylglutaryl coenzyme A] reductase inhibitor), (2) manumycin A ( MA ; FPT inhibitor), (3) perillyl alcohol ( GGPT 1 and -2 inhibitor), or (4) vehicle control from age 4 to 8 weeks and euthanized at 12 weeks. Histological characterization was performed. Protein analysis was completed on aortic specimens to measure ERK (extracellular signal-regulated kinase) signaling. In vitro Fbn1C1039G/+ aortic smooth muscle cells were utilized to measure Ras-dependent ERK signaling and MMP (matrix metalloproteinase) activity. Pravastatin and MA significantly reduced aneurysm growth compared with vehicle control (n=8 per group). In contrast, PA did not significantly decrease aneurysm size. Histology illustrated reduced elastin breakdown in MA -treated mice compared with vehicle control (n=5 per group). Although elevated in control Marfan mice, both phosphorylated c-Raf and phosphorylated ERK 1/2 were significantly reduced in MA -treated mice (4-5 per group). In vitro smooth muscle cell studies confirmed phosphorylated cR af and phosphorylated ERK 1/2 signaling was elevated in Fbn1C1039G/+ smooth muscle cells (n=5 per group). Fbn1C1039G/+ smooth muscle cell Ras-dependent ERK signaling and MMP activity were reduced following MA treatment (n=5 per group). Corroborating in vitro findings, MMP activity was also decreased in pravastatin-treated mice. Conclusions Aneurysm reduction in Fbn1C1039G/+ mice following pravastatin and MA treatment was associated with a decrease in Ras-dependent ERK signaling. MMP activity can be reduced by diminishing Ras signaling.