Safety of fondaparinux in the prevention of venous thromboembolism in elderly medical patients: results of a single-center, retrospective study.

AIM: Venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality in acutely ill medical patients. Fondaparinux is recommended for the prevention of VTE in this setting, but little information is available on its safety and effectiveness in unselected, "real world" patients. The aim of this paper was to assess the safety and efficacy of fondaparinux in elderly acutely ill medical patients. METHODS: Single center, retrospective study. All patients >60 years, admitted for acute medical disease, bedridden for at least four days and treated with fondaparinux were evaluated. Occurrence of objectively documented, symptomatic VTE, and of bleeding events during the treatment period and follow-up were reported. RESULTS: Two hundred and ten patients (median age 81 years) were treated with fondaparinux. Seventy patients received fondaparinux 1.5 mg daily, 140 received the 2.5 mg daily dose. However, 29 patients in the first group (with a CrCl≥50 mL/min) and 84 patients in the last group (with a CrCl<50 mL/min) did not receive the correct dose of fondaparinux. During treatment, one episode (0.48%, 95% CI 0.1% to 2.6%) of major bleeding and 6 episodes (2.86%, 95% CI 1.3% to 6.1%) of clinically relevant non major bleeding were recorded. Only one thromboembolic event (0.48%, 95% CI 0.1% to 2.6%) was documented. Thirty-nine patients died; no death was related to VTE, unlike one death was due to major bleeding. Cancer was the only significant predictor of bleeding at statistical analysis. CONCLUSION: In elderly acutely ill hospitalized medical patients, thromboprophylaxis with fondaparinux 2.5 or 1.5mg daily is safe and effective in preventing VTE without increasing bleeding risk.

Fibrinogen kinetics and protein turnover in hypertension: Effects of insulin.

BACKGROUND AND AIM: Hyperfibrinogenemia, a cardiovascular risk factor, is frequent in hypertension and largely unexplained. In this study, we measured fibrinogen production and whole-body protein turnover under both basal and hyperinsulinemic states, in hypertensive [H] and control [C] subjects, using a leucine stable isotope tracer and precursor-product relationships. METHODS AND RESULTS: Since hypertension is often a feature of the "metabolic", insulin resistance syndrome, which in turn affects both fibrinogen kinetics and whole-body protein turnover, we selected hypertensive subjects without the metabolic syndrome. Following basal measurements, an euglycemic, approximately euaminoacidemic, hyperinsulinemic clamp was performed, with plasma insulin raised to 700-900 pmol/L. In H, rates of the fractional and absolute synthesis (FSR and ASR, respectively) of fibrinogen were 30%-40% greater (p<0.05 or less) than in C in both states, whereas leucine turnover was normal. Hyperinsulinemia did not modify fibrinogen synthesis in either group with respect to baseline, whereas it suppressed leucine appearance from endogenous proteolysis by approximately 40% to same extent in both groups. Amino acid clearance was similar in both the H and C subjects. In H, the insulin-mediated glucose disposal (M) was approximately 25% lower, (although insignificantly) than in controls, showing no overall insulin resistance. There was an inverse correlation between M and fibrinogen FSR during the clamp. CONCLUSIONS: In essential hypertension fibrinogen production is increased, is not further stimulated by insulin, and is inversely related to insulin sensitivity at high-physiological insulin concentrations. Amino acid disposal and basal as well as insulin-responsive protein degradation rates are instead normal.

Short-term arterial blood reperfusion of normothermic kidney in renal artery and abdominal aorta reconstructive surgery.

OBJECTIVE: to prevent kidney injury in renal artery and juxta-renal aortic surgery. After 30 min of cross-clamping ischaemia, renal arterial inflow is temporary re-established for 3 min. The aim of the study was to retrospectively analyse the results of this original technique. METHODS: between January 1987 and May 1999, 48 patients underwent kidney short-term arterial blood reperfusion, directly or through the Pruitt-Inahara shunt. The reperfusion was repeated every 30 min of ischaemia, whenever necessary. Fifty control patients underwent <30 min of kidney ischaemia. Patients were assessed by serum creatinine, digital angiography and radioisotope renography using technecium(99). RESULTS: in the study group one patient developed an acute renal failure and died (2% (-95% CI: 0-11%)). In both study and control groups patients showed a similar and moderate but temporary decline in renal function, which returned to preoperative levels after 1 week. CONCLUSIONS: the results of this study indicate that kidney short-term reperfusion may protect renal tissue from prolonged cross-clamping ischaemia (up to 100 min), also in patients considered at high risk for acute renal failure.

Surgical treatment of atherosclerotic lesions of subclavian artery: carotid-subclavian bypass versus subclavian-carotid transposition.

BACKGROUND: The aim of this retrospective study is to analyze the short and long term results of two different surgical treatments in patients with subclavian lesions: common carotid-subclavian artery bypass (CSB) versus transposition of subclavian artery on the common carotid artery (SCT). METHODS: From 1981 until 1995, 40 non randomized patients with symptomatic subclavian steal underwent 20 CSBs and 20 SCTs. Risk factor rates were equally balanced in the two groups. Surgery was carried out routinely under general anesthesia, with electroencephalic continuous monitoring. Patency of revascularization was assessed by physical examination, brachial blood pressure determinations, ultrasound sonography and angiography whenever recurrence of symptoms developed or when the function of repair was in doubt. Patients were examined every year. In Spring 1996 (range 9-189 mos, average 7 years) a general clinical-instrumental follow-up was performed. RESULTS: In the short term (<30 days) mortality was 5%: one death (5%) for pulmonary embolism in a patient with CSB and one for myocardial infarction in a patient with SCT. The early thrombosis rate was 5% (1 CSB and 1 common carotid artery distal to a patent SCT). During follow-up 10 patients (25%) died and 6 were lost. The six-year actuarial patency rate was 100% for SCT and 66% for CSB. Moreover there were 3 thromboses of the vertebral artery homolateral to patent CSBs. CONCLUSIONS: In conclusions SCT should be considered the surgical technical choice for the treatment of proximal subclavian artery lesions.

Unconjugated hyperbilirubinaemia in HBV carriers. Discriminant value of nicotinic acid (NA) test.

Recently an unconjugated hyperbilirubinaemia, without any other abnormalities in liver function test, in 14.3% of HBV Japanese carriers has been noticed. Therefore, it would be possible to argue that the persistent infection of HBV in hepatocytes might play a role in an hypothetical metabolic derangement of bilirubin clearance. Twenty-five subjects in a group of 468 HBsAg+ patients (equal to 5.33%) presented an hyperbilirubinaemia. This percentage was not different from the 5.83% found in 3083 HBsAg- controls coming from the same institution. Therefore we could exclude that in our population the presence of HBV surface antigen itself would determine a statistically higher level of total bilirubin (TB) than in controls. The nicotinic acid (NA) loading test may reveal some bilirubin metabolic defects (i.e. Gilbert syndrome), even in subjects with normal basal values of TB. According to this background, we performed in 11 HBsAg+ males with basal TB higher than 17.1 mumol/l (1 mg%) (group A/1), 13 HBsAg+ males with basal TB lower or equal to 17.1 mumol/l (group A/2) and 14 HBsAg- normal controls matched for sex and age (group B) the NA test according to Röllinghoff et al. All the parameters calculated by the NA test resulted significantly different in the A/1 group compared with the B group, but not different from those found by several authors in the Gilbert's syndrome. On the contrary, no significant differences have been noticed between the latter group and the A/2 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases.

In 67 patients (mean age 51 years, range 26-79), at diagnosis of primary haemochromatosis (PH), grade III or IV liver iron overload was present in all cases, cirrhosis in 85%, transferrin saturation greater than 80% in 75%, serum ferritin greater than 1000 micrograms/l in 84%, and overt diabetes in 48%. Alcohol intake was greater than 150 g/day in 11 patients; six were chronic hepatitis B surface antigen (HBsAg) carriers. HLA-A3 and B7 antigens were present in 64% and 23% versus respectively 22% (p less than 0.01) and 9% (p less than 0.025) in controls. Iron overload was found in the stomach, duodenum, skin and bone marrow in 57, 43, 45 and 59% of the patients studied. Sixty-three patients were followed for 1-260 months (median 24); 43 received regular iron-depleting treatment and 20 did not because of liver failure, cancer or refusal. Cumulative survival was 79%, 67% and 61% at 1, 4 and 10 years, respectively. Ten patients died from hepatocellular carcinoma and two from extrahepatic cancer. The early high mortality rate was due to some cases of advanced disease or cancer. Cumulative survival in the regularly treated group was 95% at 1 year and 91% at 4 and 10 years, which was higher than in the untreated group.

Estimation of the hepatic blood "flow" by galactose plasma clearance in patients with liver disease.

Following intravenous administration of 500 mg/kg b.wt. galactose, Galactose Elimination Capacity (GEC, mg/min/kg) was determined in 24 subjects with chronic non-cirrhotic liver disease (CLD), 33 with liver cirrhosis and 11 controls. GEC was significantly (P less than 0.01) reduced in both CLD and cirrhosis. A statistically significant difference (P less than 0.01) was present between these two groups. Following the plasma disappearance curve at concentrations below 1.25 mmol/l, at which the extraction coefficient is assumed to be equal to one, the "Efficient Hepatic Blood Flow" (EHBF, ml/min) was determined in 11 consecutive cirrhosis patients, seven patients with CLD and 11 controls. EHBF was normal or slightly reduced in CLD as compared to controls (1046 +/- 216 vs. 1471 +/- 156 ml/min, mean +/- SEM, n.s.) whereas it was markedly reduced in cirrhosis (846 +/- 96 ml/min, mean +/- SEM, p less than 0.001). Interestingly, a significant linear correlation (r = 0.757, p less than 0.001) was present between EHBF and the plasma clearance of sulfobromophthalein. No correlation was present, on the other hand, between the value of GEC and that of EHBF. These data indicate that after a single intravenous injection of galactose, the hepatic blood flow passing through the enzymatically active parts of the liver (i.e. excluding shunts) can be measured.

Serum type III procollagen peptide in alcoholic liver disease and idiopathic hemochromatosis: its relationship to hepatic fibrosis, activity of the disease and iron overload.

To assess the value of type III procollagen peptide (sPIIIP) as a marker of hepatic fibrosis, sera from 73 patients with alcohol-related liver disease and 30 patients with idiopathic hemochromatosis (IHC) were studied by a specific radioimmunoassay. sPIIIP was increased in 87% of 30 patients with cirrhosis, in 16% of 32 with steatofibrosis but in none of 11 with steatosis. There was a significant correlation with histologic hepatocellular necroinflammation (r = 0.42, p less than 0.01), but not with hepatic fibrosis. sPIIP was increased in 33% of 30 patients with IHC, whether or not they had cirrhosis or fibrosis, and whatever the level of iron overload or the extent of the hepatic deterioration. IHC patients with increased levels of sPIIIP had a higher prevalence of superimposed hepatic damage than did those with normal procollagen levels (p less than 0.05). Our findings, therefore, weaken the diagnostic value of sPIIIP as an index of connective tissue deposition in the liver, and suggest that, at least in alcohol-related liver disease and IHC, hepatocellular necroinflammation influences the results.