Platelet electrical resistance for measuring platelet activation and adhesion in human health and disease.

BACKGROUND: The ability to measure changes in platelet reactivity is important to identify novel aspects of platelet biology and develop targeted therapeutics to prevent bleeding or thrombosis. Current platelet function testing allows for single agonist analysis at a time. The ability to phenotype platelets in a single assay with multiple agonists and adhesion substrates could yield more insights into altered pathways than are feasible with current approaches. We hypothesized platelet electrical resistance (PER) could be used for more comprehensive phenotyping of platelets. METHODS: Platelets were isolated from male and female healthy donors (age 39.6 ± 6.9) and septic patients (age 44.0 ± 13.5). PER 96-well plates were coated with various substrates, including fibrinogen and collagen. Platelets were added to the coated plates in the presence or absence of thrombin or convulxin. Platelet activation and spreading was monitored by measuring changes in electrical impedance. RESULTS: Platelets adhesion to fibrinogen and collagen increased impedance. In addition, impedance increased in response to thrombin or convulxin. No changes in impedance were observed in the absence of platelets or when wells were uncoated, indicating changes in impedance were directly due to platelet adhesion and activation. Inhibiting integrin αIIbß3 decreased impedance when fibrinogen was used as a substrate, consistent with platelet-dependent effects. Platelets from septic patients caused increased impedance compared to healthy donors, demonstrating this assay can be used to assess platelet hyperreactivity. CONCLUSION: PER can be applied as a high throughput tool to measure platelet reactivity in health and disease, where platelet activation is increased.

Cholecystostomy: Are we using it correctly?

BACKGROUND: Percutaneous Cholecystostomy Tubes (PCT) have become an accepted and common modality of treating acute cholecystitis in patients that are not appropriate surgical candidates. As percutaneous gallbladder drainage has rapidly increased newer research suggests that the technique may be overused, and patients may be burdened with them for extended periods. We examined our experience with PCT placement to identify independent predictors of interval cholecystectomy versus destination PCT. METHODS: All patients with cholecystitis initially treated with PCT from 2014 to 2017 were stratified by whether they underwent subsequent interval cholecystectomy. Demographic data, initial laboratory values, Tokyo Grade, Charlson Comorbidity Index, ASA Class, complications related to PCT, complications related to cholecystectomy, and mortality data were retrospectively collected. Descriptive statistics, univariable, and multivariable Poisson regression were performed. RESULTS: 165 patients received an initial cholecystostomy tube to treat cholecystitis. 61 (37%) patients went on to have an interval cholecystectomy. There were 4 complications reported after cholecystectomy. A total of 46 (27.9%) deaths were reported, only one of which was in the cholecystectomy group. Age, Tokyo Grade, liver function tests, ASA Class, and Charlson Comorbidity Index were significantly different between the interval cholecystectomy and no-cholecystectomy groups. Univariable regression was performed and variables with p < 0.2 were included in the multivariable model. Multivariable Poisson regression showed that increasing Tokyo Grade (IRR 0.454, p = 0.042, 95% CI 0.194-0.969); and increasing Charlson Comorbidity Score (IRR 0.890, p = 0.026, 95% CI 0.803-0.986) were associated with no-cholecystectomy. Higher Albumin (IRR 1.580, p = 0.011, 95% CI 1.111-2.244) was associated with having an interval cholecystectomy. CONCLUSION: Patients in the no-cholecystectomy group were older, had more comorbidities, higher Tokyo Grade, ASA Class, and initial liver function test values than those that had interval cholecystectomy. Since interval cholecystectomy was performed with a low rate of complications, we may be too conservative in performing cholecystectomy after drainage and condemning many patients to destination tubes.