Evaluation Of Embolic Protection Devices For Fat Emboli Prevention
Cardiovascular System & Cardiology; Surgery
Background: Patients with acutely treated femoral shaft fractures with reamed intramedullary nailing are at risk for acute respiratory distress syndrome due to liberation of bone marrow fat particles that travel to the lung and cause damage to the parenchyma. The purpose of this study was to demonstrate: (1) the ability of clinically applicable embolic protection devices to capture such particles; (2) how such a device affects cardiopulmonary function after reamed intramedullary nailing; and (3) evaluation of lung pathology to determine whether filtration affects pulmonary embolic load. Methods: A total of 12 canines were anesthetized, and hemodynamic monitoring was established. Carotid embolic protection devices were introduced into the iliac vein, and ipsilateral intramedullary reaming and nailing was performed. Cardiopulmonary parameters were recorded at timed intervals up to 60 minutes after the procedure. The control group (n = 4) was compared with groups treated with Accunet (n = 4) and Spider (n = 4) filters. A blinded histopathological review was performed on lung specimens to determine the average number of emboli per section and to measure the area (mm(2)) of embolic load by digital image analysis. Results: Gross inspection of the embolic protection devices showed the presence of bone marrow debris. A significant change was observed in pH levels (control = -0.052, filters = +0.005; P < .05) within the 60 minutes after intramedullary nailing. Serum bicarbonate (meq/dL) values were noted to have similar changes of -2.7 and -1.8 at 10 and 60 minutes, whereas the experimental group was +0.6 and +0.8 at the same time intervals (P = .01 and .0004, respectively). Pulmonary measurements for pO(2) and oxygen saturation were analogous to the serum parameters with decreases in the control group in comparison with the filter groups. The mean numbers of emboli and area measurements of embolic load were significantly reduced in the filter group (all P < .01). Conclusions: Embolic protection devices were effective in capturing embolic debris from reamed intramedullary nailing of lower extremity long bones and demonstrated a protective effect on pulmonary function and significantly decreased the number and size of emboli in the lung. Based on these findings, patients with long bone fractures at risk for pulmonary complications and acute respiratory distress syndrome could benefit from the placement of embolic protection devices prior to intramedullary fixation. While this study utilized filtration devices designed for carotid embolic protection, further study is warranted to determine optimal filter design in this setting.
Lanzinger W; Caldwell J; Schoenfeld A; Horne W; Sloan P; Stakleff K S; Zink J; Netzley R; Wright D
Journal of Vascular Surgery-Venous and Lymphatic Disorders
2013
2013-01
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.jvsv.2012.07.012" target="_blank" rel="noreferrer noopener">10.1016/j.jvsv.2012.07.012</a>
Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis
drugs; efficacy; gold; low-dose methotrexate; ocular safety; pharmacokinetics; placebo; plasma; Rheumatology; serum concentrations; trial
Objective. A dose-response relationship for hydroxychloroquine (HCQ), in terms of the proportion of patients achieving the Paulus 20% criteria for improvement, had previously been observed in patients with rheumatoid arthritis (RA) receiving a 6-week loading regimen of 400, 800, or 1,200 mg HCQ daily. This present retrospective analysis was performed to investigate possible relationships between the blood HCQ and HCQ-metabolite concentrations and measures of efficacy and toxicity. In addition, we sought to ascertain whether further investigation of HCQ/HCQ-metabolite levels might lead to testing of one of these substances as a new antirheumatic drug. Methods. Patients with active RA (n = 212) began a 6-week, double-blind trial comparing 3 different doses of HCQ at 400, 800, or 1,200 mg/day, followed by 18 weeks of open-label HCQ treatment at 400 mg/day. Patients were repeatedly evaluated for treatment efficacy and toxicity. Blood samples were available from 123 patients for analysis of HCQ, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ) levels using high-performance liquid chromatography. Achievement of the modified Paulus 20% improvement criteria for response in RA was used as the primary efficacy parameter. Spontaneously reported adverse events were categorized and analyzed as toxicity outcome variables. The relationship between response (efficacy and toxicity) and drug levels was evaluated using logistic regression analysis. Results. The subset of patients with blood concentration data was equivalent to the larger study population in all demographic and outcome characteristics. The mean HCQ, DHCQ, and DCQ elimination half-lives were 123, 161, and 180 hours, respectively. There was a positive correlation between the Paulus 20% improvement criteria response and blood DHCQ concentrations during weeks 1-6 (P < 0.001). A potential relationship between ocular adverse events and BDCQ levels was found (P = 0.036). Logistic regression analysis of adverse events data showed that adverse gastrointestinal events were associated with higher HCQ levels (P = 0.001-0.021) during weeks 1, 2, and 3. Conclusion. There is a weak, but predictable, relationship between blood DHCQ concentrations and efficacy of treatment with HCQ. In addition, there is an association between gastrointestinal adverse events and elevated blood HCQ concentrations. Further investigation of these relationships is warranted to see if DHCQ may be introduced as a new antirheumatic drug.
Munster T; Gibbs J P; Shen D; Baethge B A; Botstein G R; Caldwell J; Dietz F; Ettlinger R; Golden H E; Lindsley H; McLaughlin G E; Moreland L W; Roberts W N; Rooney T W; Rothschild B; Sack M; Sebba A I; Weisman M; Welch K E; Yocum D; Furst D E
Arthritis and Rheumatism
2002
2002-06
Journal Article
<a href="http://doi.org/10.1002/art.10307" target="_blank" rel="noreferrer noopener">10.1002/art.10307</a>