Outcome of visceral chimney grafts after urgent endovascular repair of complex aortic lesions.

OBJECTIVE: Endovascular abdominal aortic repair requires an adequate sealing zone. The chimney graft (CG) technique may be the only option for urgent high-risk patients who are unfit for open repair and have no adequate sealing zone. This single-center experience provides long-term results of CGs with endovascular repair for urgent and complex aortic lesions. METHODS: Between July 2006 and October 2012, 51 patients (16 women) with a median age of 77 years (interquartile range, 72-81 years), were treated urgently (within 24 hours [61%]) or semiurgently (within 3 days [39%]) with endovascular aortic repair and visceral CGs (n = 73). Median follow-up was 2.3 years (interquartile range, 0.8-5.0 years) for the whole cohort, 3 years for 30-day survivors, and 4.8 years for patients who are still alive. RESULTS: Five patients (10%) died within 30 days. All of them had a sacrificed kidney. All-cause mortality was 57% (n = 29), but the chimney- and procedure-related mortality was 6% (n = 3) and 16% (n = 8), respectively. Chimney-related death was due to bleeding, infection, renal failure, and multiple organ failure. There were two postoperative ruptures; both were fatal although not related to the treated disease. The primary and secondary long-term CG patencies were 89% (65 of 73) and 93% (68 of 73), respectively. Primary type I endoleak (EL-I) occurred in 10% (5 of 51) of the patients, and only one patient had recurrent EL-I (2%; 1 of 51). No secondary endoleak was observed. Chimney-related reintervention was required in 16% (8 of 51) of the patients because of EL-I (n = 3), visceral ischemia (n = 4), and bleeding (n = 2). The reinterventions included stenting (n = 5), embolization (n = 3), and laparotomy (n = 2). Thirty-one visceral branches were sacrificed (9 celiac trunks, 9 right, and 13 left renal arteries). Among the 30-day survivors, 8 of 17 patients (47%) with a sacrificed kidney required permanent dialysis; of these, seven underwent an urgent index operation. The aneurysm sac shrank in 63% (29 of 46) of cases. CONCLUSIONS: The 6% chimney-related mortality and 93% long-term patency seem promising in urgent, complex aortic lesions of a high-risk population and may justify a continued yet restrictive applicability of this technique. Most endoleaks could be sealed endovascularly. However, sacrifice of a kidney in this elderly cohort was associated with permanent dialysis in 47% of patients.

Decreasing incidence of ruptured abdominal aortic aneurysm already before start of screening.

BACKGROUND: The aim of this study was to evaluate whether screening for abdominal aortic aneurysm (AAA) has led to a decrease in ruptured AAA (rAAA) incidence. METHOD: The Malmö population was evaluated regarding the incidence of rAAA and elective AAA surgery 4 years before and after start of AAA-screening in 2010. Data from 1971 to 1986 (J Vasc Surg 18:74-80, 1993) and 2000-2004 (J Vasc Surg 44:237-43, 2006), enabled analysis of trends over time. RESULTS: Analysis of time-periods 1971-1986, 2000-2004, 2006-2010 and 2010-2014 showed an incidence of rAAA of 5.6 (4.9-6.3), 10.6 (8.9-12.4), 6.1 (4.6-7.6) and 4.0 (2.9-5.1), respectively. In men aged 60-69 years the incidences were 16.0 (10.7-21.3), 45.6 (27.7-63.4), 19.3 (9.2-35.3) and 8.9 (2.8-20.6), respectively. The incidences of elective AAA surgery in men aged 60-69 years were 22.9 (16.5-29.2), 34.6 (19.1-50.2), 9.7 (1.2-18.5) and 44.2 (27.0-61.6), respectively. CONCLUSIONS: A decrease in incidence of rAAA in men was evident before the implementation of screening. We were yet not able to demonstrate a certain reduction in rAAA incidence after the start of screening.

Efficacy and durability of the chimney graft technique in urgent and complex thoracic endovascular aortic repair.

OBJECTIVE: This study reports the early and midterm to long-term experience of chimney grafts (CGs) in urgent endovascular repair of complex lesions in the thoracic aorta. METHODS: Twenty-nine high-risk patients (20 men) who were unfit for open repair were treated using CG technique for ruptured (n = 14) or symptomatic (n = 15) aortic lesions engaging the aortic arch itself (n = 9), the descending aorta (n = 10), or the thoracoabdominal aorta (n = 10). Twenty-two patients (76%) were treated urgently (≤24 hours) and seven were semiurgent (≤3 days). Of 41 chimneys used, 24 were placed in supra-aortic branches and 17 in visceral branches. Median follow-up (interquartile range) for the entire cohort was 2 years (0.6-3.8 years), 2.5 years (1-4 years) for 30-day survivors, and 3.5 years (1.9-6.4 years) for those who were still alive. RESULTS: Four patients (14%) died ≤30 days of cerebral infarction (n = 1), visceral ischemia secondary to the initial rupture (n = 1), multiple organ failure (n = 1), or heart failure (n = 1). There were 11 late deaths (38%); however, only two deaths were related to the CG technique. The primary and secondary technical success rates were 86% (25 of 29) and 97% (28 of 29), respectively. The secondary patency rate of CGs was 98%. Seventeen (68%) of the aortic lesions shrank significantly. Three patients (10%) had primary type I endoleak and another three (10%) had secondary type I endoleak. The endoleaks were managed with Onyx (ev3 Endovascular, Inc, Plymouth, Minn) or coil embolization (n = 2), restenting (n = 1), and conversion to open repair (n = 2). One secondary endoleak is still under observation after >20 months. All primary endoleaks and one secondary endoleak originated from CGs in the brachiocephalic trunk (4 of 6 [67%]). CONCLUSIONS: The midterm to long-term results of the CG technique for urgent and complex lesions of the thoracic aorta in high-risk patients are promising, with low early mortality and long durability of the CGs. More patients with longer follow-up are still needed.

Inflammatory mediators after endovascular aortic aneurysm repair.

OBJECTIVE: To evaluate patterns of inflammatory mediators before and after elective endovascular aortic aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: Inflammatory mediators including soluble urokinase plasminogen activator (suPAR), endothelin (ET)-1, tumour necrosis factor (TNF)-α, interleukin (IL)-6, CD40 ligand (CD40L) and IgM antibodies against phosphorylcholine (IgM anti-PC), were evaluated before and after elective EVAR in 21 patients. Five patients undergoing open AAA repair (OR) were evaluated for comparison. RESULTS: SuPAR (p<0.001), ET-1 (p=0.003) and IL-6 (p=0.02) increased whereas IgM anti-PC decreased (p<0.001) after EVAR. Both suPAR (p=0.04) and IL-6 (p=0.03) increased in the five patients with unchanged/expanded aneurysm sac after EAR, whereas only suPAR increased (p=0.04) and IL-6 remained unchanged (p=0.2) among the 16 patients with shrinking aneurysm sac. No difference was noted between patients undergoing EVAR and OR regarding levels or changes of studied markers. CONCLUSIONS: These changes in plasma biomarker profile are compatible with on-going inflammatory activation in AAA patients after EVAR. The potential role of IL-6 as a plasma biomarker for treatment failure in surveillance programs after EVAR needs to be further evaluated.

Equal access to health care may diminish the differences in outcome between native and immigrant patients with type 1 diabetes.

BACKGROUND/OBJECTIVE: Previous studies have found that ethnicity influences glycemic control. We hypothesized that differences between Nordic and non-Nordic patients are less pronounced for children with type 1 diabetes in high incidence countries in Northern Europe. RESEARCH DESIGN AND METHODS: We investigated patients aged 0-15 yr in national pediatric registers in Denmark (D), Iceland (I), Norway (N), and Sweden (S) (2006-2009). Ethnic origin was defined by maternal country of birth as being Nordic or non-Nordic (other countries). RESULTS: The cohort (n = 11,908, 53.0% boys, onset age 7.7 (3.9) yr, diabetes duration 6.1 (3.6) yr, [mean, (SD)]) comprised 921 (7.7%) non-Nordic patients. The frequencies of non-Nordic patients according to country of residence were: 5.7% (D), 2.7% (I), 5.5% (N), and 9.4% (S). Sex distribution and BMI z-score did not differ between Nordic and non-Nordic patients, but non-Nordic patients were 0.5 yr younger at onset than Nordic patients (p < 0.0006). Non-Nordic patients had a lower number of daily insulin bolus injections and higher daily insulin doses compared to their Nordic peers. Patients of non-Nordic origin had slightly higher HbA1c levels (0.6-2.9 mmol/mol, p < 0.001) and, with the exception of Norway, were less frequently treated with CSII (p = 0.002) after adjusting for confounders. CONCLUSIONS: The reported differences in glycemic regulation between Nordic and non-Nordic type 1 diabetes children and adolescents in four Nordic countries are diminutive, but persist after accounting for treatment intensity.

Islet cell antibodies (ICA) identify autoimmunity in children with new onset diabetes mellitus negative for other islet cell antibodies.

AIMS: The aim of this study was to explore whether islet cell antibodies (ICA) could be identified in children with newly onset diabetes mellitus but negative for autoantibodies against glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), insulin (IAA), or any of the three variants with arginine (R), tryptophan (W), or glutamine (Q) at position 325 of the zinc transporter 8 (ZnT8A). METHODS: A population-based analysis of autoantibodies was performed from 1 May 2005 to 2 September 2010 in Swedish children newly diagnosed with diabetes. ICA was analyzed with an enzyme-linked immunosorbent assay and if positive, reanalyzed in the classical ICA immunofluorescence assay, in 341 samples among 3545 children who had been tested negative for all of GADA, IA-2A, IAA, or ZnT8A (R, W, Q). RESULTS: An isolated positivity for ICA was identified in 5.0% (17/341) of the newly diagnosed children. The levels of ICA in positive subjects ranged from 3 to 183 JDF-U (median 30). This finding increased the diagnostic sensitivity of islet autoimmunity as 3204/3545 patients (90.4%) were islet autoantibody positive without the ICA analyses and 3221 patients (90.9%) were positive with the inclusion of ICA. CONCLUSIONS: The finding of an isolated positivity for ICA despite negativity for GADA, IA-2A, IAA, and ZnT8A (R, W, Q) suggests that still another yet unidentified autoantigen(s) may contribute to the ICA immunofluorescence. Hence, ICA is important to analyze in type 1 diabetes children and adolescents that would otherwise be islet autoantibody negative.

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.

Chimney grafts preserve visceral flow and allow safe stenting of juxtarenal aortic occlusion.

OBJECTIVE: Chimney grafts have proven useful for urgent endovascular repair of juxtarenal aortic aneurysms. Stenting of juxtarenal aortic occlusive disease is not routinely advocated due to the risk of visceral artery obstruction. We report on the potential applicability of chimney grafts in 10 patients with juxtarenal aortic stenosis or occlusion. To our best knowledge, chimney grafts have not been applied previously in this challenging setting. METHODS: Ten high-risk female patients (mean age, 68 years) with severe stenosis or occlusion of the aorta at the level of the visceral arteries were offered stenting. "Chimney" stents or stent grafts (20-40 mm long) were implanted from a brachial approach into visceral arteries that needed to be covered by the aortic stent. The chimney stents were then temporarily obstructed by balloon catheters to prevent visceral embolization until the aortic stent or stent graft was deployed. RESULTS: All procedures were technically successful, and patency was obtained in all visceral arteries and the aorta without distal embolization. One patient died after 9 days of acute heart failure. The nine surviving patients presented no complications, and all stented vessels remained patent at up to 6 years. Another patient died after 5.5 years due to lung cancer. All three patients with renal impairment have improved renal function, and a reduction in antihypertensive medication has been possible. CONCLUSIONS: Chimney grafts may allow stenting of juxtarenal aortic occlusive disease by protecting the patency of visceral arteries. Further evaluation with more patients and longer follow-up is required.

The importance of socioeconomic factors for compliance and outcome at screening for abdominal aortic aneurysm in 65-year-old men.

OBJECTIVE: To evaluate compliance with screening and prevalence of abdominal aortic aneurysm (AAA) in relation to background data regarding area-based socioeconomic status. METHODS: Our department annually invites 4300 65-year-old men from the city of Malmö and 15 neighboring municipalities to ultrasound AAA screening. In a cross-sectional cohort study, compliance and AAA prevalence among 8269 men were related to background socioeconomic data such as mean income, proportion of immigrants, percentage of subjects on welfare, smoking habits, and unemployment rate in the different municipalities. The 10 different administrative areas in Malmö were evaluated separately. RESULTS: Compliance with screening in the entire area was 6630/8269 (80.2%) but varied between 64.4% and 89.3% in different municipalities (P < .001). In univariate analysis, compliance increased with increasing mean income (r = 0.873; P < .001) but decreased with increasing proportion of immigrants (r = -0.685; P =.005) and subjects on welfare (r = -0.698; P = .004). Compliance in 10 different administrative parts of Malmö (P = .002) also increased with increasing mean income (r = 0.948; P < .001), and decreased with increasing proportion of immigrants (r = -0.650; P = .042) and increasing unemployment rate (r = -0.796; P = .006). Altogether, 117 (1.8%) AAAs were found, the prevalence differing between both different municipalities (P =.003) and the 10 different administrative parts of Malmö (P =.02). The prevalence of AAA in the 10 administrative parts of Malmö increased with increasing percentage of smokers (r = 0.784; P = .007), percentage of immigrants (r = 0.644; P = .044), and unemployment rate (r = 0.783; P =.007) but decreased with increasing mean income (r = -0.754; P = .012). CONCLUSIONS: Compliance with ultrasound screening for AAA differed between different geographical areas. In areas with low socioeconomic status, compliance rates were lower, whereas AAA prevalence was higher. The identification of contextual factors associated with low compliance is important to be able to allow targeted actions to increase efficacy of ultrasound screening for AAA. Targeted actions to increase compliance in those areas are being scientifically investigated and implemented.

External quality assessment of HbA1c and its effect on comparison between Swedish pediatric diabetes clinics. Experiences from the Swedish pediatric diabetes quality register (Swediabkids) and Equalis.

BACKGROUND: To explore to what extent measurement error can explain the variation of mean patient HbA(1c) between clinics. METHODS: For each year 2005-2010 data from 5380-6985 children, age <18 years, in 35-43 Swedish pediatric clinics was analyzed. Each year 13,000-19,000 HbA(1c) analyses were evaluated. Year mean HbA(1c) for each patient was calculated for HbA(1c) values when insulin dose was ≥0.5 U/kg. In Sweden HbA(1c) values were during the study period standardized to the Mono S level, HbA(1c)(Mono S)%, but are given also in the international unit HbA(1c)(IFCC), mmol/mol. Performance of locally measured HbA(1c) is monitored by Equalis through monthly external quality assessment (EQA) schemes. RESULTS: The yearly mean bias term for each clinic varied from -0.54 to 0.41 HbA(1c)(Mono S)%. The bias between clinic HbA(1c) and target value improved during the 6 years and the mean bias was for 79%-88% of clinics within the recommended level ±0.14 HbA(1c)% the last 2 years. Inter-clinic mean HbA(1c) had a wide interquartile range, 0.30-0.43 HbA(1c)(Mono S)% [3.2-4.5 HbA(1c)(IFCC)mmol/mol]. CONCLUSIONS: Regular participation in EQA schemes is necessary when comparing HbA(1c) values. The measurement error decreased during the 6-year period and explained from 28% to <10% of the inter-clinic variation in year mean clinic HbA(1c).

APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] µg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 µg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

APC resistance due to Factor V Leiden is not related to baseline inflammatory mediators or survival up to 10 years in patients with critical limb ischemia.

To prospectively evaluate the potential influence of resistance to activated protein C (APC-resistance) on the initial inflammatory response, amputation rate and survival during 10 years of follow-up in patients with critical limb ischemia (CLI). Two hundred and fifty-six consecutive CLI patients were analyzed for APC-ratio, the Factor V Leiden mutation and inflammatory mediators and then prospectively followed for 10 years. Inflammatory mediators, amputation rate, morbidity and mortality were compared between patients with and without APC resistance. Of the 256 CLI patients, 35 (14 %) were heterozygotes and 2 (1 %) homozygotes for the Factor V gene mutation, whereas 219 (86 %) patients were non-APC resistant. No significant differences were found between APC resistant and non-APC resistant patients regarding inflammatory mediators. Non-APC resistant patients more often had infrainguinal atherosclerosis (172 [79 %] vs 22 [59 %]; p = 0.017). Amputation rate at 1 year did not differ. Furthermore, there were no significant differences between groups regarding 1-, 3-, 5-, or 10-year survival. APC resistance in patients with CLI was not related to inflammatory activity, and had no impact on limb salvage or rate of amputation or long-term mortality. APC-resistant CLI-patients less frequently had infrainguinal arteriosclerosis, however.

Socioeconomic factors and concomitant diseases are related to the risk for venous thromboembolism during long time follow-up.

While the risk for arterial vascular disease has been shown to be influenced by socioeconomic status (SES), there is limited information whether SES also influences the risk for venous thromboembolism (VTE). To evaluate whether there is an association between SES and VTE incidence. In 1990, all 730,050 inhabitants (379,465 women and 350,585 men) above 25 years of age in the County of Skåne in Sweden were evaluated with regard to age, household income, marital status, country of birth, number of years of residence in Sweden, educational level, and concomitant diseases. The cohort was hereafter prospectively investigated regarding diagnosis of, or death from VTE (deep venous thrombosis or pulmonary embolism ), during 1991-2003. The association between socioeconomic data and concomitant diseases at the baseline investigation 1990 and incidence of VTE during follow-up was examined by Cox proportional hazard models. During the 13 years prospective follow-up, 10,212 women and 7,922 men were diagnosed with VTE. In both genders, age above 40 years at baseline, low income, single status, and a lower level of education were associated with an increased risk of VTE. However, both men and women born outside of Sweden have a lower risk for VTE during follow-up, however. Age above 40 years, low income, single marital status, and lower level of education were independently related to an increased risk of VTE diagnosis during 13 years of prospective follow-up.

Hormonal response during physical exercise of different intensities in adolescents with type 1 diabetes and healthy controls.

BACKGROUND: Physical activity is a critical component in the care of diabetes. Although it offers health benefits it presents challenges. OBJECTIVE: To investigate differences between adolescent boys and girls with type 1 diabetes and healthy controls in terms of maximal work capacity (VO(2) max) and hormonal response to physical exercise of different intensities. SUBJECTS: Twelve individuals (six boys and six girls; age 14-19 yr, pubertal stage 4-5) with type 1 diabetes (duration, 6.3 ± 4.4 yr; hemoglobin A1c, 63 ± 10 mmol/mol) were compared with 12 healthy controls matched for age, sex, pubertal stage, body mass index standard deviation score, and amount of regular physical activity. METHODS: During consecutive days, three different workloads; maximal, endurance, and interval, were performed on an Ergometer cycle. During the tests, levels of lactate, glucose, insulin, and regulatory hormones [glucagon, cortisol, growth hormone (GH), adrenaline, and noradrenaline] were measured in blood. Subcutaneous glucose was measured continuously. RESULTS: VO(2) max did not differ between the groups, diabetes 49.8 ± 9.9 vs. control 50.7 ± 12.0 mL/min/kg. Hormonal responses did not differ between the groups except for mean peak GH level during the interval test, diabetes 63.2 ± 27.0 vs. control 33.8 ± 20.9 mU/L, p < 0.05. CONCLUSIONS: Physical capacity and hormonal regulation of blood glucose in connection with physical exercise of different intensities did not differ between adolescents with diabetes and healthy controls. Thus, adolescents with type 1 diabetes can participate in physical activity on the same terms as healthy peers.

Catheter-directed foam sclerotherapy treatment of saphenous vein incompetence.

BACKGROUND: The aim of this study is to report the short-term results of catheter-directed foam sclerotherapy (CDFS) in the treatment of axial saphenous vein incompetence. PATIENTS AND METHODS: Data of all patients undergoing CDFS for symptomatic primary incompetence of the great or small saphenous vein were prospectively collected. Treatment results in terms of occlusion rate and patients' grade of satisfaction were analysed. All successfully treated patients underwent clinical and duplex follow-up examinations one year postoperatively. RESULTS: Between September 2006 and September 2010, 357 limbs (337 patients) were treated with CDFS at our institution. Based on the CEAP classification, 64 were allocated to clinical class C3 , 128 to class C4, 102 to class C5 and 63 to class C6. Of the 188 patients who completed the one year follow up examination, 67 % had a complete and 14 % a near complete obliteration of the treated vessel. An ulcer-healing rate of 54 % was detected. 92 % of the patients were satisfied with the results of treatment. We registered six cases of thrombophlebitis and two cases of venous thromboembolism, all requiring treatment. CONCLUSIONS: The short-term results of CDFS in patients with axial vein incompetence are acceptable in terms of occlusion and complications rates.

Impact of intrasac thrombus and a patent inferior mesenteric artery on EVAR outcome.

PURPOSE: To assess the significance of a patent inferior mesenteric artery (IMA) and presence of intrasac thrombus on the outcome of endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA). METHODS: Between June 2004 and June 2007, 114 AAA patients (100 men; mean age 75 years, range 56-87) treated electively with a bifurcated stent-graft were assessed with computed tomography pre- and postoperatively. Incidences of type II endoleaks and reinterventions were compared with preoperative intrasac thrombus and IMA patency. RESULTS: Over a mean follow-up of 19 months (range 6-38), there was no aneurysm rupture. Eleven (11%) of 101 patients with and 7 (54%) of 13 patients without preoperative intrasac thrombus presented with a type II endoleak (p<0.01). The postoperative change in aneurysm diameter was 0 mm (-20 to 16) in 18 patients with type II endoleak and -9 mm (-30 to 18) in sealed aneurysms (p<0.001). Fourteen (78%) type II endoleaks originated from lumbar arteries and 4 (22%) from the IMA in spite of the fact that most patients (69%) had a patent IMA. There were 5 reinterventions for type II endoleak with expansion of the sac. The reinterventions did not seem related to intrasac thrombus or a patent IMA. Prophylactic embolization of the IMA was unsuccessful in 4 (33%) cases. CONCLUSION: In this series, type II endoleaks inhibited sac shrinkage and occurred more frequently in aneurysms without intrasac thrombus. Most type II endoleaks originated from lumbar arteries and not from the IMA. Prophylactic embolization of the IMA does not seem justified and is not always technically successful.

Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies.

AIM: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients. METHODS: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients <18 yr registered within the Better Diabetes Diagnosis (BDD) study (May 2005 to September 2008) were included. Participants were classified into three groups: Swedish, non-Swedish, and Mixed-origin patients according to country of origin of two generations (parents and grandparents). These groups were compared with respect to T1DM HLA markers and islet autoantibodies [glutamic acid decarboxylase autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and islet antigen-2 autoantibodies (IA-2Ab)]. RESULTS: Only 30 (1.5%) patients were born outside Sweden. Swedish patients constituted 66%, non-Swedish patients 8%, Mixed origins 17%, and 9% were of uncertain origin. Confirmed T1DM in patients within the study was 22 (95% CI: 21-23) patients/10(5)/yr rate for Swedish patients compared with 14 (95% CI: 13-15) among non-Swedish patients. The HLA-DQ8 haplotype (p < 0.0001) and DQ2/8 genotype (p < 0.02) predominated among Swedish compared with non-Swedish patients. In contrast, DQ2 was the most frequent haplotype among non-Swedish patients [OR = 1.5 (95% CI: 1.0-2.0), p < 0.04]. Multiple (≥2) autoantibodies (p < 0.04) and specifically IA-2Ab (p < 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p < 0.001). CONCLUSION: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA-DQ2 genetic markers and are diagnosed more often with GAD65Ab.

The effect of low molecular weight heparin (dalteparin) on duration and initiation of labour.

It has recently been reported that women treated with low molecular weight heparin (LMWH) during pregnancy had 3 h shorter duration of delivery. The aim of the present study was to evaluate whether LMWH (dalteparin) affects labour. From January 1996 to December 2005, 217 consecutive pregnancies, out of 34 216 newborn (prevalence 0.6%) that were given thromboprophylaxis with dalteparin (usually 5,000 IU once daily). These 217 consecutive pregnancies were compared to an unselected control group (n = 1,499) of gravidae. Main outcome was time in first and second stage of labour and gestational age at delivery. Among nulliparous women, there were significantly fewer women with prolonged first stage of labour as compared to controls (4.1% vs. 8.5%, P = 0.047). In addition, the duration of first stage of labour was 1 h shorter among those treated with LMWH (5.2 vs. 6.2 h, P = 0.06). There were no such differences among parous women. The risk of prematurity, profuse blood loss, and postpartum anaemia was almost doubled among those treated with LMWH (11.5% vs. 5.9%, P = 0.002, 10.6% vs. 5.9%, P < 0.001, and 12.9% vs. 8.7%, P = 0.048, respectively). Treatment with a prophylactic dose of LMWH (dalteparin) during pregnancy was related to fewer women with prolonged first stage of labour, but also to an increased risk of prematurity and blood loss complications.

Activated protein C-protein C inhibitor complex in peripheral arterial disease.

BACKGROUND: Thrombin activation measured by the levels of the complex between activated protein C (APC) and the protein C inhibitor (PCI) is elevated in several atherosclerotic disorders. The aim of this study was to evaluate whether levels of the APC-PCI complex are related to the prognosis in peripheral arterial disease (PAD). Longitudinal study performed at the Vascular Centre, Malmö University Hospital, Sweden. METHODS: APC-PCI complex levels were analyzed in 268 consecutive patients hospitalized for PAD and in 42 healthy controls (median age, 74 years). Patients (n = 35) with warfarin treatment less than 4 weeks before APC-PCI sampling were excluded from analysis. Data-based medical records of all 233 remaining patients (median age, 72 [64-79] years) were searched for vascular events such as hospitalization because of atherosclerotic disease, operative or endovascular recanalization of peripheral arteries, transtibial or transfemoral amputation because of PAD, acute coronary syndrome, stroke, or death. RESULTS: Median duration of follow-up was 16 months (interquartile range, 12-23 months). APC-PCI complex levels were higher in PAD patients than in controls (0.240 [0.180-0.320] microg/L vs. 0.140 [0.190-0.220] microg/L; p < 0.0001) but not associated with an increased risk for death (p = 0.2054) or events during follow-up (p = 0.2850). Independent predictors of future events were low b-hemoglobin (p = 0.0084), high b-leukocytes (p = 0.0034), and history of a previous vascular event (p = 0.0032). Age (p = 0.0286), high p-creatinine (p = 0.0165), and history of a previous event (p = 0.0311) were independent predictors of death. CONCLUSION: APC-PCI complex levels were higher in PAD patients than in controls, but did not predict the clinical outcome. The effect of a possible prethrombotic state, as reflected in increased APC-PCI levels, on prognosis and severity of atherosclerotic disease has to be further investigated.

Complement activation and plasma levels of C4b-binding protein in critical limb ischemia patients.

OBJECTIVE: Critical limb ischemia (CLI) is a peripheral arterial disease manifested by drastically diminished blood flow to the legs, pain at rest, nonhealing wounds, and gangrene caused by atherosclerosis. Significant tissue necrosis is associated with late stage CLI and the patients have a poor prognosis. Necrotic and apoptotic cells activate complement and bind complement inhibitor C4b-binding protein (C4BP). The major isoform of C4BP is composed of seven identical alpha-chains and one beta-chain, here termed C4BP(beta), whereas upon inflammation a normally less abundant isoform is upregulated that is exclusively composed of alpha-chains. Measuring the alpha-chains of C4BP includes both isoforms and is termed total C4BP (C4BP(tot)). The hypothesis of this study was that levels of complement activation and C4BP are predictive for the severity of the disease and that their measurement might be of clinical advantage. METHODS: This was a prospective, single-center study of 259 consecutive patients with CLI admitted to a secondary referral center for vascular diseases. Interventions included evaluation of soluble terminal complement complexes (C5b-9), C4BP(tot) and C4BP(beta), lipid levels, the inflammatory mediators tumor necrosis factor-alpha, interleukin-6, 8-iso-prostaglandin F(2alpha), high-sensitivity C-reactive protein, neopterin, plasma homocysteine, and plasma endothelin-1 in plasma as well as resistance to activated protein C and ankle blood pressure. All data were compared with an age-matched population based control group of 219 currently healthy individuals. RESULTS: The data are presented as mean +/- SEM/median. CLI patients showed systemic complement activation (1.17 +/- 0.06/1.13 AU/mL vs 0.69 +/- 0.07/0.59 AU/mL in healthy controls, P < .0001), which was even higher in patients with gangrene (1.33 +/- 0.11/1.28 AU/mL vs 1.1 +/- 0.08/1.0 AU/mL, P = .0264), who also showed increased C4BP levels (421 +/- 28.6/386 microg/mL vs 341 +/- 10.8/318 microg/mL for C4BP(tot), P = .0248; 374 +/- 25.4/332 microg/mL vs 305 +/- 9.5/285 microg/mL for C4BP(beta), P = .0581). C4BP plasma levels were significantly elevated in CLI patients in comparison to healthy controls (351 +/- 8.1/322 microg/mL vs 297 +/- 8.0/288 microg/mL for C4BP(tot), P = .0001; 314 +/- 7.0/287 microg/mL vs 265 +/- 7.0/263 microg/mL for C4BP(beta), P = .0004) and correlated to levels of interleukin-6 (P(tot/beta) = .0048/.0019), high-sensitivity C-reactive protein (P < .0001), leukocyte (P(tot/beta) = .0086/.0043) and platelet count (P = .0001), LDL/HDL ratio (P(tot) = .0151) and HDL (P(tot/beta) = .0047/.0177), but not to tumor necrosis factor-alpha. CONCLUSIONS: Increased complement activation and C4BP plasma levels are related to the degree of tissue necrosis and disease severity of critical limb ischemia. This knowledge in combination with the found correlations to other biomarkers is useful for understanding the pathophysiology of the disease.