Treatment of aortic graft infection by in situ reconstruction with Omniflow II biosynthetic prosthesis.

Currently available conduits for in situ reconstruction after excision of infected aortic grafts have significant limitations. The Omniflow II vascular prosthesis is a biosynthetic graft associated with a low incidence of infection that has succesfully been used in the treatment of infected infrainguinal bypass. We report on the first use of the Omniflow II prosthesis for in situ reconstruction after aortic graft infection.A bifurcated biosynthetic bypass was created by spatulating and anastomosing two 8-mm tubular Omniflow II grafts. This bypass was used for in situ reconstruction after excision of infected aortic grafts in three cases. After a mean follow-up of 2.2 years, no occlusion, degeneration, or rupture of the Omniflow II grafts was observed. Although one patient suffered from graft reinfection, the bypass retained structural integrity and no anastomotic dehiscence was observed.Treatment of aortic graft infection by in situ reconstruction with the Omniflow II vascular prosthesis is feasible. Its resistance to infection and off-the-shelf availability make this graft a promising conduit for aortoiliac reconstruction.

The effect of rosiglitazone on asymmetric dimethylarginine (ADMA) in critically ill patients.

Asymmetric dimethylarginine (ADMA) plays a crucial role in the arginine-nitric oxide pathway. Critically ill patients have elevated levels of ADMA which proved to be a strong and independent risk factor for ICU mortality. The aim of this study was to investigate the effect of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist rosiglitazone on ADMA plasma levels in critically ill patients. In a randomized controlled pilot study, ADMA, arginine and symmetric dimethylarginine (SDMA) were measured in 21 critically ill patients on the intensive care unit (ICU). Twelve patients received 4mg rosiglitazone once a day for a maximum of 6 weeks or until discharge or death. Nine patients served as control patients. In addition, total sequential organ failure assessment (SOFA score), kidney function and liver function were determined. Compared to the ADMA levels of healthy individuals as specified in earlier studies, ADMA plasma levels of critically ill patients were significantly higher (0.42+/-0.06 versus 0.73+/-0.2micromol/L, respectively; p<0.001). Both ADMA (B=3.5; 95% CI: 0.5-6.5; p=0.023) and SDMA (B=1.7; 95% CI: 0.7-2.7; p=0.001) were independently related to SOFA scores. Overall, rosiglitazone treatment had no effect on ADMA levels, which only significantly differed between the rosiglitazone and control groups at day 7 (p=0.028). The SOFA score in the rosiglitazone group was lower compared to the control group but the difference was only statistically significant at day 10 (p=0.01). In conclusion, in critically ill patients plasma ADMA levels were elevated and associated with the extent of multiple organ failure, but no significant ADMA-lowering effect of the PPAR-gamma agonist rosiglitazone was observed.

The prognostic value of severe malnutrition in the development of nonthyroidal illness in head and neck cancer patients.

BACKGROUND: Thyroid hormone metabolism is modulated by starvation and overfeeding but also by dietary composition. Unfortunately, little is known about the effect of malnutrition on disease-induced nonthyroidal illness (NTI). In this study, we investigated whether the degree of NTI after surgery differed between severely malnourished and well-fed patients with head and neck cancer. METHODS: Plasma levels of the thyroid hormones 3',5-triiodothyronine (T(3)), reverse T(3) (rT(3)), free T(4) (FT(4)), and thyrotropin (TSH) were measured on the first day before the operation and on the first, fourth, and seventh day after the operation in 16 malnourished patients who were admitted for intentional curative surgery of T1-T4 carcinomas of the head and neck. Six well-fed head and neck cancer patients eligible for surgical treatment served as a control group. RESULTS: In the malnourished group, rT(3) showed a significant increase, whereas T(3) and FT(4) decreased significantly due to the operation. TSH showed no significant change. During the postoperative course, it took 7 days until rT(3) and 4 days until T(3) and FT(4) were restored to their preoperative value. In contrast, well-fed patients did not develop NTI. CONCLUSIONS: This study shows that peri- and postoperative rT(3), T(3), and FT(4) levels change significantly in malnourished patients compared with well-fed patients. Therefore, it can be concluded that nutrition status of patients undergoing major head and neck surgery should be optimized in order to prevent the development of NTI.

The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA).

BACKGROUND AND AIMS: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. Although both dimethylarginines may be important regulators of the arginine-NO pathway, their metabolism is largely unknown. Both dimethylarginines are removed from the body by urinary excretion. However, ADMA is also subject to enzymatic degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which is highly expressed in the liver. To elucidate the role of the liver in the metabolism of ADMA, we aimed to investigate dimethylarginine handling of the liver in detail. METHODS: Ten male Wistar rats were used for this study. Blood flow was measured using radiolabeled microspheres according to the reference sample method. Concentrations of dimethylarginines were measured by HPLC. The combination of arteriovenous concentration difference and organ blood flow allowed calculation of net organ fluxes and fractional extraction rates. RESULTS: Both the liver (0.89+/-0.11) and the kidney (0.68+/-0.06) showed a high net uptake (nmol/100 g body weight (BW)/min) of ADMA, whereas a significant net uptake of SDMA was only observed in the kidney (0.34+/-0.04). For the liver, fractional extraction rates were 29.5% +/-3.0 for ADMA and 0.0%+/-3.7 for SDMA. Fractional extraction rates of ADMA and SDMA for the kidney were 36.0%+/-2.7 and 31.6%+/-3.8, respectively. CONCLUSIONS: The liver plays an important role in the metabolism of ADMA by taking up large amounts of ADMA from the systemic circulation.

Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality.

BACKGROUND AND AIMS: Accumulation of asymmetrical dimethylarginine (ADMA) has been linked to endothelial dysfunction, and is an important risk factor for cardiovascular disease. Its elimination from the body is dependent on urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase. This enzyme is highly expressed in the liver, and in rat studies a high net hepatic uptake of asymmetrical dimethylarginine was found. In critically ill patients, we investigated the relation between indicators of renal and hepatic dysfunction and plasma ADMA concentration, and tested the association between ADMA concentration and outcome. METHODS: We prospectively collected blood samples from a cross-section of critically ill patients (n=52) with clinical evidence of dysfunction of more than two organs. We identified correlates of plasma ADMA concentration with laboratory values, organ failures score and outcome by univariate and multiple regression analyses. RESULTS: In critically ill patients, plasma ADMA concentration was independently related to the presence of hepatic failure (b=0.334, 95% CI: 0.207-0.461; P<0.001), and to lactic acid (b=0.395, 95% CI: 0.230-0.560; P<0.001) and bilirubin (b=0.121, 95% CI: 0.031-0.212; P=0.009) concentration as markers of hepatic function. Twenty-one (40%) patients deceased during their ICU stay. In a logistic regression model, plasma ADMA ranked as the first and strongest predictor for outcome, with a 17-fold (95% CI: 3-100) increased risk for ICU death in patients who were in the highest quartile for ADMA. CONCLUSIONS: In critically ill patients, plasma ADMA concentration is a strong and independent risk factor for ICU mortality, and hepatic dysfunction is the most prominent determinant of ADMA concentration in this population.

Low arginine plasma levels in patients after thoracoabdominal aortic surgery.

OBJECTIVE: Thoracoabdominal aortic surgery is a high-risk procedure and associated with a significant morbidity and mortality. Ischemia reperfusion of visceral organs and lower extremities is one of the most important determinants of this morbidity. Arginine is the precursor of nitric oxide and arginine plasma levels are important in maintaining organ blood flow. Furthermore, arginine is important in wound healing and the immune system. Because of increased utilization of arginine, low arginine plasma levels could be expected after thoracoabdominal aortic surgery. We therefore measured arginine plasma levels in these patients. DESIGN: Six patients with thoracoabdominal aortic aneurysm were included in this study. SETTING: University Hospital Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands. SUBJECTS: Six patients undergoing thoracoabdominal aortic surgery. INTERVENTION: Plasma levels of arginine were measured by high-performance liquid chromatography. RESULTS: Very low arginine plasma levels were seen on the first postoperative day. From day 1 arginine slowly increased, but did not reach normal plasma levels on day 6. CONCLUSIONS: A significant decrease of arginine plasma levels was found and because of the fact that arginine has multiple functions, it may be important to keep these arginine plasma levels at normal or even higher levels in patients undergoing major vascular surgery. European Journal of Clinical Nutrition (2000) 54, 615-617.

High plasma arginine concentrations in critically ill patients suffering from hepatic failure.

OBJECTIVE: In physiological conditions, the liver plays an important role in the regulation of plasma arginine concentrations by taking up large amounts of arginine from the hepatic circulation. When hepatic failure is present, arginine metabolism may be disturbed. Therefore, we hypothesized high arginine plasma concentrations in critically ill patients suffering from hepatic failure. DESIGN: We prospectively collected blood samples from a cross-section of intensive care unit patients. SETTING: Surgical intensive care unit of a Dutch university medical center. SUBJECTS: A total of 52 critically ill patients with clinical evidence of dysfunction of more than two organs were recruited. MEASUREMENTS: Plasma arginine concentrations were determined by HPLC. We identified correlations of arginine concentrations with organ failure scores and laboratory variables by univariate and multiple regression analyses. RESULTS: High plasma arginine concentrations were found in critically ill patients developing organ failure. Patients who were in the highest quartile of plasma arginine concentrations had significantly lower fibrinogen concentrations, higher lactic acid concentrations, and longer prothrombin time. Stepwise multiple regression analysis showed that concentrations of arginine were independently associated with the presence of hepatic failure (P=0.03) and renal failure (P=0.048). In addition, lactic acid proved to be an independent determinant of plasma arginine concentration (P=0.014). CONCLUSIONS: Critically ill patients who suffer from hepatic failure have elevated plasma arginine concentrations. Additional arginine in the treatment of these patients can be harmful, and therefore should not be used as a standard nutritional regimen until further evaluation.

Survival of malnourished head and neck cancer patients can be predicted by human leukocyte antigen-DR expression and interleukin-6/tumor necrosis factor-alpha response of the monocyte.

BACKGROUND: Patients with advanced stages of head and neck cancer are often characterized by malnutrition and by an impaired immune system. Because some of the suppressed immune parameters were shown to be of prognostic importance in trauma and sepsis, we investigated whether these would also correlate with survival in head and neck cancer. METHODS: Severely malnourished head and neck cancer patients undergoing ablative and reconstructive surgery were followed prospectively and their perioperative immune parameters were related to long-term survival. RESULTS: Forty-nine patients with a preoperative weight loss of more than 10% were followed up for a period of at least 16 months after surgery. Analyses of variance revealed that preoperative human leukocyte antigen-DR (HLA-DR) expression on monocytes and endotoxin-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were different between patients who survived and patients who died. Proportional hazards identified a weight loss of more than 12%, the presence of coexistent disease, and an HLA-DR expression on monocytes below the cutoff points (mean fluorescence index < 15, peak channel index < 9) to be of significant influence on survival. CONCLUSIONS: In addition to known prognostic parameters such as tumor stage, coexistent disease, and weight loss, the immune parameters HLA-DR expression on monocytes and endotoxin-induced cytokine production may carry prognostic value in cancer patients. Immunomodulating therapies leading to improvement of these parameters might in the future lead to increased options for treatment.

Aortic aneurysm repair is associated with a lower inflammatory response compared with surgery for inflammatory bowel disease.

BACKGROUND: Since the plasma cytokine profile reflects the body's inflammatory response to injury, this study was designed to prospectively observe the plasma cytokine levels in response to the degree of different sorts of abdominal surgical trauma. METHODS: Plasma levels of TNF-alpha, type I TNF receptor (p55), type II TNF receptor (p75), IL-6, IL-8, IL-10, phospholipase A(2) (PLA(2)), and haptoglobin were measured peri-operatively in patients undergoing bowel resection for inflammatory bowel disease or diverticulitis (IBD) (n = 9), elective repair of abdominal aortic aneurysm (AAA) (n = 9), or laparoscopic cholecystectomy (lap chole) (n = 9). RESULTS: The IBD patients showed a significant (p < 0.05) post-operative elevation in plasma IL-6, p55, p75, and PLA(2) levels, but no significant change in TNF-alpha, IL-8, IL-10 or haptoglobin levels. The AAA patients had a significant post-operative rise in IL-10 levels and a significant decrease in plasma haptoglobin levels, but no significant change of TNF-alpha, IL-6, IL-8, p55, p75, or PLA(2) concentrations. The lap chole patients demonstrated no significant change in any of these parameters. CONCLUSION: These data show that IL-6, IL-10, p55, and p75 are markers to measure the degree of inflammatory stress associated with abdominal operative procedures and demonstrate the relative lack of a cytokine response to laparoscopic cholecystectomy.