Natural History of Thoracic Aortic Aneurysms: Size Matters,Plus Moving Beyond Size

Thoracic aortic aneurysms (TAAs) are a prevalent and deadly disease that, without diagnosis and treatment, eventuates in life-threatening aortic dissection or rupture. While TAAs normally grow in an indolent manner, once a certain size (a “hinge point”) is reached, the risk of dissection, rupture, and death increases dramatically. By virtue of their common clinical “silence,” many TAAs are not diagnosed until such complications occur. While size is a helpful criterion for intervention, there is a need for parameters and markers besides aortic aneurysm size for use in diagnosing and monitoring TAAs so as to prevent natural complications of this disease.     

Does Total Ankle Arthroplasty Belong in the Comprehensive Care for Joint Replacement?

The Comprehensive Care for Joint Replacement (CJR) model seeks to lower costs and improve quality for primary lower extremity joint replacements. This includes total ankle arthroplasty (TAA), which is performed far less frequently than total hip (THA) and knee (TKA) arthroplasty. We used the SPARCS database to identify 537 TAA and 239,053 elective primary THA or TKA procedures from 2009 to 2014, excluding hip fractures. Compared with THA and TKA, TAA had a shorter mean length of stay (2.2 versus 3.2 days), greater mean cost ($20,817 versus $17,613), lower rate of disposition to nursing and rehabilitation facilities (17% versus 52%), and lower rate of 90-day readmission (4.9% versus 5.8%). In multivariable-adjusted regression models of TAA versus THA and TKA, length of stay was 30% shorter (p?<?.001), costs were 14% greater (p?<?.001), and risk of disposition to nursing and rehabilitation facilities was 86% lower (p?<?.001), with no significant difference in 90-day readmission (p?=?.957). Patients undergoing TAA had different patterns of short-term resource usage compared with patients undergoing THA and TKA, most notably higher short-term costs. The economic viability of TAA is threatened by alternative payment models that reimburse hospitals for TAA at the same rate as THA and TKA.     

Nitroflurbiprofen, a nitric oxide-releasing cyclooxygenase inhibitor, improves cirrhotic portal hypertension in rats

BACKGROUND & AIMS: We studied whether administration of nitroflurbiprofen (HCT-1026), a cyclooxygenase inhibitor with nitric oxide (NO)-donating properties, modulates the increased intrahepatic vascular tone in portal hypertensive cirrhotic rats. METHODS: In vivo hemodynamic measurements (n = 8/condition) and evaluation of the increased intrahepatic resistance by in situ perfusion (n = 5/condition) were performed in rats with thioacetamide-induced cirrhosis that received either nitroflurbiprofen (45 mg/kg), flurbiprofen (30 mg/kg, equimolar concentration to nitroflurbiprofen), or vehicle by intraperitoneal injection 24 hours and 1 hour prior to the measurements. Additionally, we evaluated the effect of acute administration of both drugs (250 micromol/L) on the intrahepatic vascular tone in the in situ perfused cirrhotic rat liver (endothelial dysfunction and hyperresponsiveness to methoxamine) and on hepatic stellate cell contraction in vitro. Typical systemic adverse effects of nonsteroidal anti-inflammatory drugs, such as gastrointestinal ulceration, renal insufficiency, and hepatotoxicity, were actively explored. RESULTS: In vivo, nitroflurbiprofen and flurbiprofen equally decreased portal pressure (8 +/- 0.8 and 8.4 +/- 0.1 mm Hg, respectively, vs 11.8 +/- 0.6 mm Hg) and reduced the total intrahepatic vascular resistance. Systemic hypotension was not aggravated in the different treatment groups (P = .291). In the perfused cirrhotic liver, both drugs improved endothelial dysfunction and hyperresponsiveness. This was associated with a decreased hepatic thromboxane A(2)-production and an increased intrahepatic nitrate/nitrite level. In vitro, nitroflurbiprofen, more than flurbiprofen, decreased hepatic stellate cells contraction. Flurbiprofen-treated rats showed severe gastrointestinal ulcerations (bleeding in 3/8 rats) and nefrotoxicity, which was not observed in nitroflurbiprofen-treated cirrhotic rats. CONCLUSIONS: Treatment with nitroflurbiprofen, an NO-releasing cyclooxygenase inhibitor, improves portal hypertension without major adverse effects in thioacetamide-induced cirrhotic rats by attenuating intrahepatic vascular resistance, endothelial dysfunction, and hepatic hyperreactivity to vasoconstrictors.     

Significance and therapeutic potential of endothelial progenitor cell transplantation in a cirrhotic liver rat model

BACKGROUND & AIMS: We investigated whether endothelial progenitor cell (EPC) transplantation could reduce established liver fibrosis and promote hepatic regeneration by isolating rat EPCs from bone marrow cells. METHODS: Recipient rats were injected intraperitoneally with carbon tetrachloride (CCl(4)) twice weekly for 6 weeks before initial administration of EPCs. CCl(4) was then readministered twice weekly for 4 more weeks, and EPC transplantation was carried out for these same 4 weeks. RESULTS: At 7 days in culture, the cells expressed Thy-1, CD31, CD133, Flt-1, Flk-1, and Tie-2, suggesting an immature endothelial lineage. Immunohistochemical analyses showed fluorescent-labeled, transplantation EPCs were incorporated into the portal tracts and fibrous septa. Single and multiple EPC transplantation rats had reduced liver fibrosis, with decreased alpha2-(I)-procollagen, fibronectin, transforming growth factor-beta, and alpha-smooth muscle actin-positive cells. Film in situ zymographic analysis revealed strong gelatinolytic activity in the periportal area, in accordance with EPC location. Real-time polymerase chain reaction analysis of multiple EPC-transplantation livers showed significantly increased messenger RNA levels of matrix metalloproteinase (MMP)-2, -9 and -13, whereas tissue inhibitor of metalloproteinase-1 expression was significantly reduced. Expression of hepatocyte growth factor, transforming growth factor-alpha, epidermal growth factor, and vascular endothelial growth factor was increased in multiple EPC-transplantation livers, while hepatocyte proliferation increased. Transaminase, total bilirubin, total protein, and albumin levels were maintained in EPC-transplantation rats, significantly improving survival rates. CONCLUSIONS: We conclude that single or repeated EPC transplantation halts established liver fibrosis in rats by suppressing activated hepatic stellate cells, increasing matrix metalloproteinase activity, and regulating hepatocyte proliferation.     

Indications of total ankle arthroplasty for rheumatoid arthritis: evaluation at 5 years or more after the operation

 The postoperative results of total ankle arthroplasty (TAA) were surveyed, and the indications of TAA for rheumatoid arthritis (RA) were examined. We have performed TAA in properly selected patients with indication of ankle joint destruction due to RA. The subjects were 18 RA patients (20 joints) who underwent TAA between April 1988 and April 1996. Type-ND or type-TNK Bioceram was used without cement for possible revision of TAA. No destruction of large joints was found in 8 patients, and TAA was used as part of multiple arthroplasty in 10 patients. After the operation, decrease in or disappearance of joint pain was obtained, and range of motion and improved ability to walk were secured. The clinical results were superior to those obtained for 17 joints of 17 patients who underwent ankle arthrodesis during the same period. However, a radiolucent zone was observed an X-ray examination in every case, after 8 years on average (range 5–12 years) after operation. Under present conditions, ankle arthrodesis should be used for younger patients. When no destruction of the hip or knee joint is found and the patient is 65 years of age or older, we believe TAA is indicated. In cases of multiple arthroplasty or with bilateral ankle joint destruction, TAA appears to be useful if patients are young, considering their better life expectancy and quality of life. Received: April 30, 2002 / Accepted: August 26, 2002