The Hardman index in patients operated on for ruptured abdominal aortic aneurysm: A systematic review.

BACKGROUND: The aims of the present study were to (1) analyze preoperative predictors for outcome suggested by Hardman and surgical mortality after open repair and endovascular repair (EVAR) of ruptured abdominal aortic aneurysms (rAAA), and (2) further evaluate the Hardman index in a systematic review. METHODS: Patients operated on for rAAA during a 5-year period between 2000 and 2004 were scored according to Hardman-1 point for either age >76 years, loss of consciousness after presentation, hemoglobin <90 g/L, serum creatinine >190 micromol/L or electrocardiographic (ECG) signs of ischemia-with blinded evaluation of ECGs by a specialist in clinical physiology. The results were included in a systematic review of studies evaluating the Hardman index. RESULTS: In-hospital mortality after operation was 41% (67/162). There was no difference in in-hospital mortality between open repair (n = 106) and EVAR (n = 56), whereas the Hardman index was associated with operative mortality in our institution and in the systematic review of 970 patients (P < .001). Mortality rate in patients with Hardman index > or =3 was 77% in the pooled analysis. A full data set of all five scoring variables was obtained in 94 (58%) of 162 patients in our study, and potential underscoring was thus possible in 68 patients. Of the available ECGs, 12 (8.7%) of 138 were judged nondiagnostic. Five studies did not state their missing data on ECG and hemoglobin and serum creatinine concentrations, nor did they specify the criteria for ECG ischemia. CONCLUSIONS: A strong correlation between the Hardman index and mortality was found. A Hardman index > or =3 cannot be used as an absolute limit for denial of surgery. The utility of the Hardman index seems to be impeded by variability in scoring resulting from missing or nondiagnostic data.

Fatal colonic ischemia: A population-based study.

OBJECTIVES: To estimate the incidence of fatal colonic ischaemia (CI) and the cause-specific mortality of CI, and to describe the localization and extension of colonic infarction and quantify the risk factors associated with CI. MATERIAL AND METHODS: Between 1970 and 1982 the autopsy rate in Malmö, Sweden, was 87%, creating the possibilities for a population-based study. Out of 23,446 clinical autopsies, 997 cases were coded for intestinal ischaemia in a database. In addition, 7569 forensic autopsy protocols were analysed. In a case-control study nested in the clinical autopsy cohort, four CI-free controls, matched for gender, age at death and year of death, were identified for each fatal CI case in order to evaluate the risk factors. RESULTS: The cause-specific mortality ratio was 1.7/1000 autopsies. The overall incidence of autopsy-verified fatal CI was 1.7/100,000 person years, increasing with age up to 23/100,000 person years in octogenarians. Fatal cardiac failure (odds ratio (OR) 5.2), fatal valvular disease (OR 4.3), previous stroke (OR 2.5) and recent surgery (OR 3.4) were risk factors for fatal CI. Narrowing/occlusion of the inferior mesenteric artery (IMA) at the aortic origin was present in 68% of the patients. The most common segments affected by transmural infarctions were the sigmoid (83%) and the descending (77%) colon. CONCLUSIONS: Heart failure, atherosclerotic occlusion/stenoses of the IMA and recent surgery were the main risk factors causing colonic hypoperfusion and infarction. Segments of transmural infarctions were observed within the left colon in 94% of the patients. Awareness of the diagnosis and its associated cardiac comorbidities might help to improve survival.

New concepts in optimal management of anticoagulant therapy for extended treatment of venous thromboembolism.

Recent trials on secondary prophylaxis after venous thromboembolism (VTE) have provided a wealth of data on the risk factors for recurrence and, to some extent, also for bleeding. Some of the results are consistent across the studies, but there are also conflicting data. Certain risk factors, such as pulmonary embolism versus deep vein thrombosis or presence of cardiolipin antibodies, have a more pronounced influence on the risk early in the course of disease. Others, such as hereditary thrombophilic defects, seem to gain importance over many years of follow-up. Therefore, it can be difficult to make decisions on an individual patient basis. In this article, data from important and illustrative trials have been extracted and compared and controversies highlighted. The conclusions drawn should help clinicians make balanced decisions on the optimal duration of anticoagulation after an episode of VTE.

Increasing incidence of ruptured abdominal aortic aneurysm: a population-based study.

OBJECTIVE: The aim of the present population-based study was to assess the trends of age- and gender-specific incidence of ruptured abdominal aortic aneurysm (rAAA). METHODS: Patients with rAAA from the city of Malmö, Sweden, were studied between 2000 and 2004. An analysis of trends of incidence and mortality of rAAA in Malmö was possible because of a previous population-based study on patients with rAAA between 1971 and 1986 (autopsy rate 85% compared with 25% for the time period 2000 to 2004). The in-hospital registry of Malmö University Hospital and the databases at the Department of Pathology, Malmö, and the Institution of Forensic Medicine, Lund, identified patients with rAAA, and the in-hospital registry identified all elective repairs for AAA. RESULTS: Compared with the time period 1971 to 1986, the overall incidence of rAAA significantly increased from 5.6 (95 % confidence interval [CI], 4.9 to 6.3) to 10.6 (95% CI, 8.9 to 12.4) per 100,000 person-years (standardized mortality ratio, 1.6; 95% CI, 1.0 to 2.1). In men aged 60 to 69 and 70 to 79 years, the incidence increased significantly from 16 (95% CI, 11 to 21) and 56 (95% CI, 43 to 69) to 46 (95% CI, 28 to 63) and 117 (95% CI, 84 to 149) per 100,000 person-years, respectively, whereas no increase in the age-specific incidence in women could be demonstrated. The overall incidence of elective repair of AAA increased significantly from 3.4 (95% CI, 2.8 to 4.0) to 7.0 (95% CI, 5.6 to 8.4) per 100,000 person-years and increased most significantly from 12 (95% CI, 3.4 to 32) to 68 (95% CI, 34 to 102) per 100,000 person-years in men aged 80 to 89 years and from 5.1 (95% CI, 2.4 to 9.3) to 28 (95% CI, 15 to 41) per 100,000 person-years in women aged 70 to 79 years. The elective-acute repair ratio in women increased from 2.4 to 5.6 and decreased in men from 2.1 to 1.0. CONCLUSIONS: Between 1971 to 1986 and 2000 to 2004, the incidence of rAAA increased significantly, despite a 100% increase in elective repairs and notwithstanding a potential for bias towards underestimation due to lower autopsy rates in recent years. The reason behind this increase is unclear, and further studies are needed to identify risk groups for direction of effective prevention and screening.

Portal vein thrombosis: prevalence, patient characteristics and lifetime risk: a population study based on 23,796 consecutive autopsies.

AIM: To assess the lifetime cumulative incidence of portal venous thrombosis (PVT) in the general population. METHODS: Between 1970 and 1982, 23,796 autopsies, representing 84% of all in-hospital deaths in the Malmö city population, were performed, using a standardised protocol including examination of the portal vein. PVT patients were characterised and the PVT prevalence at autopsy, an expression of life-time cumulative incidence, assessed in high-risk disease categories and expressed in terms of odds ratios and 95% CI. RESULTS: The population prevalence of PVT was 1.0%. Of the 254 patients with PVT 28% had cirrhosis, 23% primary and 44% secondary hepatobiliary malignancy, 10% major abdominal infectious or inflammatory disease and 3% had a myeloproliferative disorder. Patients with both cirrhosis and hepatic carcinoma had the highest PVT risk, OR 17.1 (95% CI 11.1-26.4). In 14% no cause was found; only a minority of them had developed portal-hypertension-related complications. CONCLUSION: In this population-based study, PVT was found to be more common than indicated by previous clinical series. The markedly excess risk in cirrhosis and hepatic carcinoma should warrant an increased awareness in these patients for whom prospective studies of directed intervention might be considered.

Trousseau's syndrome - what is the evidence? A population-based autopsy study.

Despite numerous studies documenting the association between cancer and venous thromboembolism (VTE), the reason for the excessive risk in certain cancers remains obscure. No large-scale studies have yet investigated the independent effects of cancer type, site and growth pattern. Between 1970 and 1982, 23,796 standardised autopsies were performed, representing 84% of all in-hospital deaths in an urban Swedish population. The relationship between cancer and PE was evaluated with logistic regression. The overall PE prevalence was 23%, and 10% of the population had a fatal PE. Forty-two per cent of pancreatic cancer patients had PE (OR 2.55; 95% CI 2.10-3.09) (p<0.001); gall bladder, gastric, colorectal and pulmonary adenocarcinomas were similarly independently associated with PE. In comparison with squamous cell lung cancer, patients with pulmonary adenocarcinoma had 1.65 times higher odds for PE (95% CI 1.20-2.29). Adenocarcinoma and metastatic cancer were independently associated with PE risk (OR 1.27; 95% CI 1.16-1.40; p<0.001, and OR 1.10;95% CI 1.01-1.20; p=0.024, respectively) but when controlling for cancer type and spread, pancreatic cancer was still associated with an OR of 2.10 (95% CI 1.71-2.58) of PE (p<0.001). We conclude that the risk of PE in cancer patients depends not only on the cancer site and spread but also on the histological type. The excess independent risk in pancreatic cancer is intriguing and should warrant further research.

Assessment of bleeding after concomitant administration of antiplatelet and anticoagulant agents in lower limb arthroplasty.

In an analysis of the Melagatran Thrombosis Prophylaxis in Orthopedic Surgery (METHRO) III study, we evaluated whether concomitant administration of aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) with the direct thrombin inhibitor melagatran/ximelagatran or the low-molecular-weight heparin enoxaparin increased bleeding in patients undergoing major joint surgery. Further objectives were to compare the influence of the timing of initial postoperative administration of melagatran/ximelagatran on bleeding in orthopedic patients receiving ASA/NSAIDs and in comparison with the preoperative administration of enoxaparin. ASA or NSAIDs in conjunction with melagatran/ximelagatran or enoxaparin did not increase bleeding. Bleeding rates were not significantly different, irrespective of the timing of the initial postoperative dose of melagatran/ximelagatran (4-8 vs. 4-12 h) when compared with preoperative (12 h) administration of enoxaparin. Transfusion rates were significantly lower with administration of melagatran/ximelagatran compared with enoxaparin.

Incidence of myocardial infarction and death in relation to walking-induced calf pain and plasma levels of inflammation-sensitive proteins.

Walking-induced calf pain as well as levels of different inflammation-sensitive plasma proteins (ISPs) are related to cardiovascular disease (CVD). This prospective cohort study explored the relationship between ISPs and walking-related calf pain and the interrelationships between ISPs and calf pain in the prediction of death and incidence of coronary events (CE). In 5,725 apparently healthy men, 46 +/-3.0 years old, plasma concentrations of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. Walking-induced calf pain was assessed by questionnaire. Mortality and incidence of CE were monitored over a mean follow-up of 18 years in subjects defined by the presence of calf pain and ISP level (0 to 1 or 2 to 5 ISP(s) in the top quartile). The prevalence of calf pain (7.3%) was significantly related to age, lifestyle, and traditional risk factors of CVD and ISP levels. The risk factor-adjusted relative risks for CE, CVD- and all-cause mortality were 1.89 (CI: 1.27 to 2.82), 2.90 (CI: 1.82 to 4.62), and 2.67 (CI: 1.97 to 3.57), respectively, for men with calf pain and high ISP levels (reference: no calf pain and low ISP levels). The corresponding risk for those with calf pain and low ISP levels were 1.34 (CI: 0.91 to 1.97), 1.47 (CI: 0.90 to 2.41), and 1.31 (CI: 0.95 to 1.81), respectively. These results indicate, on the one hand, that walking-induced calf pain is associated with high ISP levels and, on the other, that the risk of CVD in men with calf pain is substantially higher in those with high ISP levels than in those with low levels.

Mesenteric venous thrombosis with transmural intestinal infarction: a population-based study.

OBJECTIVE: To determine the cause-specific mortality from and incidence of transmural intestinal infarction caused by mesenteric venous thrombosis (MVT) in a population-based study and to evaluate the findings at autopsy by evaluating autopsies and surgical procedures. METHODS: All clinical (n = 23,446) and forensic (n = 7569) autopsies performed in the city of Malmö between 1970 and 1982 (population 264,000 to 230,000) were evaluated. The autopsy rate was 87%. The surgical procedures were performed in 1970, 1976, and 1982. Autopsy protocols coded for intestinal ischemia or mesenteric vessel occlusion, or both, were identified in a database. In all, 997 of 23,446 clinical and 9 of 7,569 forensic autopsy protocols were analyzed. A 3-year sample of the surgical procedures, comprising 21.3% (11,985 of 56,251) of all operations performed during the entire study period, was chosen to capture trends of diagnostic and surgical activity. In a nested case-control study within the clinical autopsy cohort, four MVT-free controls, matched for gender, age at death, and year of death were identified for each fatal MVT case to evaluate the clinical autopsy findings. RESULTS: Four forensic and 23 clinical autopsies demonstrated MVT with intestinal infarction. Seven patients were operated on, of whom six survived. The cause-specific mortality ratio was 0.9:1000 autopsies. The incidence was 1.8/100,000 person years. At autopsy, portal vein thrombosis and systemic venous thromboembolism occurred in 2 of 3 and 1 of 2 of the cases, respectively. Obesity was an independent risk factor for fatal MVT (P =.021). CONCLUSIONS: The estimated incidence of MVT with transmural intestinal infarction was 1.8/100,000 person years. Portal vein thrombosis, systemic venous thromboembolism and obesity were associated with fatal MVT.

Prevalence and risk of pulmonary embolism in patients with intracardiac thrombosis: a population-based study of 23 796 consecutive autopsies.

AIMS: While right intracardiac thrombosis (IT) is a potential cause of pulmonary embolism (PE) similar to that of stroke in left-sided IT, its prevalence and prognostic significance has not been studied in the general population. The aim of this study was to assess the age- and gender-specific prevalence of IT and its relation to PE in a population-based autopsy cohort. METHODS AND RESULTS: Between 1970 and 1982, 23 796 autopsies, representing 84% of all in-hospital deaths in the Malmö city population, were performed, using a standardized procedure. The relationship between IT and PE was evaluated by cohort analyses and nested case-control studies. IT was present in 1706 (7.2%) patients, 727 and 747 of whom had right and left atrial IT, respectively. PE prevalence in patients with isolated left IT, isolated right IT, and combined IT was 28.5, 35.6, and 48.9%, with RR (95% CI) of 1.5 (1.3-1.8), 2.0 (1.6-2.5), and 3.5 (2.7-4.7), respectively, compared with age- and gender-matched controls. Patients dying from ischaemic heart disease had a 3.2 (2.7-3.6) times higher risk of right IT, which was associated with 43% PE prevalence. Of all patients with PE at autopsy, right IT was found in 354 (6.5%), and the only detected source of PE in 220 (4.0%). CONCLUSION: Right cardiac thrombosis, though difficult to assess clinically, is as common as left cardiac thrombosis and is associated with an increased risk of PE. The diagnosis should be considered in all cases of PE, especially in patients with atrial fibrillation or myocardial infarction and in the absence of confirmed deep vein thrombosis.

Clinical implications for the management of acute thromboembolic occlusion of the superior mesenteric artery: autopsy findings in 213 patients.

OBJECTIVE: To study findings at autopsy in patients with fatal acute thromboembolic occlusion of the superior mesenteric artery (SMA). SUMMARY BACKGROUND DATA: Acute occlusion of the SMA is difficult to diagnose and mortality remains high. In Malmo, Sweden, the autopsy rate between 1970 and 1982 was 87%, creating possibilities for a population-based study. METHODS: Among 23,496 clinical autopsies and 7569 forensic autopsies, 213 cases with acute thromboembolic occlusion of the SMA and intestinal infarction were identified. RESULTS: A clinical suspicion of intestinal infarction was documented in 32% of the patients, only 35% being in the care of surgeons. The embolus/thrombus ratio was 1.4 to 1. Thrombotic occlusions were located more proximally than embolic occlusions (P < 0.001), intestinal infarction was more extensive (P = 0.025) and thrombotic occlusions were associated with old brain infarction (P = 0.048), aortic wall thrombosis (P = 0.080), and disseminated cancer (P = 0.079). Patients with embolic occlusions (n = 122) had a higher frequency of acute myocardial infarction (AMI) than patients with thrombotic occlusions (P = 0.049). The embolic source was identified in 80%. In 115 (94%), synchronous embolism and/or source of embolus were present. There were findings of remaining cardiac thrombi in 58 (48%) and synchronous emboli affected 273 other arterial segments in 83 (68%). CONCLUSIONS: Early recognition and revascularization would have been a prerequisite for survival in at least half of the patients, since the jejunum, ileum, and colon were affected by infarction. A minority of all patients were under surgical care. AMI, cardiac thrombi, and synchronous emboli were common findings among patients with embolic occlusions.

Heterogeneity of cardiovascular risk among smokers is related to degree of carbon monoxide exposure.

BACKGROUND: Between smokers matched for daily tobacco consumption there are marked variations of the cardiovascular risk. This follow up of the population based cohort "Men born in 1914" from Malmö, Sweden, explored whether this is accounted for by the levels of carbon monoxide (CO). METHODS: Three hundred and sixty-five men without history of cardiovascular disease (CVD) were followed over 27 years. Leg artery disease was defined as a systolic ankle-arm pressure ratio (ABPI) below 0.9 in either leg. Incidence of myocardial infarction (MI), stroke and deaths is based on linkage with regional and national registers. The distribution of CO in blood and expired air, respectively, was divided into quartiles. RESULTS: There was a significant inverse relation between ABPI and CO in blood and expired air. Incidence of CVD events and deaths increased progressively with degree of CO exposure. Men with CO in the top quartile had significantly increased risks of CVD events (RR: 2.2; 95% CI: 1.00-4.6) and cardiovascular deaths (RR: 3.2, CI: 1.2-8.3), adjusted for daily tobacco consumption and other potential confounders. CONCLUSIONS: In smokers, the prevalence of leg atherosclerosis and incidence of cardiovascular disease is related to the amount of carbon monoxide in blood or expired air.

Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and oral ximelagatran : a multicentre study of thromboprophylaxis in elective abdominal surgery.

OBJECTIVE: The oral direct thrombin inhibitor (oral DTI) ximelagatran and its active form, melagatran, which can be administered subcutaneously, were investigated for the prevention and treatment of thromboembolic complications. DESIGN AND PATIENTS: In this randomised, double-blind, double-dummy, parallel-group study in patients (n = 90) undergoing general abdominal and/or pelvic surgery, 8-day and 35-day treatment regimens of postoperatively initiated sub-cutaneous (sc) melagatran (3mg twice daily) followed by oral ximelagatran (24mg twice daily) were compared with standard-duration sc dalteparin (5000IU) initiated preoperatively. Pharmacodynamic and pharmacokinetic parameters, efficacy (number of patients with distal and/or proximal deep vein thrombosis [DVT] verified by bilateral venography on the final day of treatment) and safety were assessed. RESULTS: The pharmacokinetics of melagatran were well described by a one-compartment model with first-order absorption after administration of both sc melagatran and oral ximelagatran. Bioavailability of melagatran was 21% after the first oral dose of ximelagatran and was virtually unchanged throughout the study. Activated partial thromboplastin time increased in a non-linear manner with plasma melagatran concentration. The overall rate of DVT was 11.4% (8/70), with events distributed evenly between treatment groups. Bleeding volumes during surgery tended to be higher in the dalteparin group than in the melagatran/ximelagatran groups. Blood transfusion volumes and numbers of patients transfused were similar in all treatment groups. CONCLUSIONS: Good bioavailability of melagatran was achieved following oral administration of ximelagatran. Postoperative sc melagatran followed by oral ximelagatran appeared to be well tolerated, and the efficacy of standard-length or prolonged prophylaxis with sc melagatran and oral ximelagatran may be comparable to that of dalteparin initiated preoperatively.

Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement.

We evaluated whether a postoperative regimen with melagatran followed by oral ximelagatran, two new direct thrombin inhibitors, was an optimal regimen for thromboprophylaxis in major orthopaedic surgery. In a double-blind study, 2788 patients undergoing total hip or knee replacement were randomly assigned to receive for 8 to 11 days either 3 mg of subcutaneous melagatran started 4-12 h postoperatively, followed by 24 mg of oral ximelagatran twice-daily or 40 mg of subcutaneous enoxaparin once-daily, started 12 h preoperatively. Ximelagatran was to be initiated within the first two postoperative days. The primary efficacy endpoint was venous thromboembolism (deep-vein thrombosis detected by mandatory venography, pulmonary embolism or unexplained death). The main safety endpoint was bleeding. Venous thromboembolism occurred in 355/1146 (31.0%) and 306/1122 (27.3%) patients in the ximelagatran and enoxaparin group, respectively, a difference in risk of 3.7% in favour of enoxaparin (p = 0.053). Bleeding was comparable between the two groups.

Prophylaxis of venous thromboembolism with subcutaneous melagatran in total hip or total knee replacement: results from Phase II studies.

The first clinical studies evaluating the safety and efficacy of melagatran, a novel, direct thrombin inhibitor, given subcutaneously as prophylaxis for venous thromboembolism (VTE) following total hip (THR) or total knee replacement (TKR) are reported. In Study I, 66 patients received subcutaneous melagatran (1.5-6 mg bid) in a poloxamer depot formulation, and in Study II, 104 patients received subcutaneous melagatran (2-4 mg bid) in saline or as a depot formulation in cyclodextrin. Treatment was given for 8-11 days, with the first dose administered immediately before surgery. Deep vein thrombosis (DVT) was assessed using mandatory bilateral venography on the last day of treatment, and pulmonary scintigraphy was performed if required. Bleeding complications occurred in the only patient who received melagatran 6 mg, and this dose-arm was discontinued. The frequency of VTE was low (12/129=9%, 95% confidence interval [CI]: 5-16%). Eight patients (6%) had distal DVT, three (2%) had proximal DVT, and in one patient (1%) pulmonary embolism (PE) was verified. In conclusion, subcutaneous melagatran 1.5-4.5 mg bid in saline or depot formulation was well tolerated and resulted in a low frequency of VTE.