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The Norwegian Offender Mental Health and Addiction study denotes the need for physical activity and anti-doping interventions in Norwegian prisons. We developed and evaluated the efficacy of such intervention-the Hercules prison program. The program combines theoretical anti-doping lessons with practical strength training. The study adopts a mixed-methods approach (pretest-posttest design) comprising a longitudinal survey, observation, informal conversations, and in-depth interviews. Survey respondents were 104 male prisoners aged 18-56 ( M = 34.81, SD = 9.34) years from seven Norwegian prisons. Of these, 52 provided both baseline and posttest responses. Participants completed questionnaires including demographic, doping use, and psychophysical items/measures. At the end of the intervention, in-depth interviews were conducted with 11 of the survey respondents. The survey data were analyzed using descriptive statistics, as well as independent and paired samples t -tests. The qualitative data were analyzed using Interpretative Phenomenological Analysis. A total of 7.5% and 33.3% of participants were current and former AAS users respectively, whereas 86.1% personally knew at least one current or former AAS user. Consistent with our expectation, there were increases in self-rated physical strength ( t = -4.1, p < 0.001, d = 0.46) and strength training self-efficacy ( t = -8.33, p < 0.001, d = 1.36), and a decrease in moral disengagement in doping ( t = -4.05, p < 0.001, d = 0.52) from baseline to posttest. These findings are supported by the qualitative data. Notable success factors are relationship-building, instructors' expertise and acceptability, and gatekeepers' navigation and co-creation. The program provides valuable evidence of the potential benefits of combining anti-doping education with practical strength training in doping prevention in correctional settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sagoe, Johnsen, Lindblad, Normann, Skogvoll, Heierdal and Lauritzen.)

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., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

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.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the proatherogenic cytokine osteopontin (OPN) in mouse arteries via local release of endothelin-1 and activation of CREB. Infusion of GIP increases plasma OPN concentrations in healthy individuals. Plasma endothelin-1 and OPN concentrations are positively correlated in patients with critical limb ischemia. Fasting GIP concentrations are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared with control subjects. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients, and expression associates with parameters that are characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration, and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from humans, mice, rats, and pigs, remarkable upregulation is observed in endothelial and smooth muscle cells upon culture conditions, yielding a "vascular disease-like" phenotype. Moreover, the common variant rs10423928 in the GIPR gene is associated with increased risk of stroke in patients with type 2 diabetes., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: The chimney graft (CG) technique was introduced to rescue accidentally covered aortic branches during aortic endovascular repair. It extends the sealing zone. There is concern about "gutter" type I endoleak (EL-I) and about the durability of CGs. The aim of the present report was to analyze the rapidly increasing existing data., Methods: A search was performed (PRISMA criteria) for all studies of visceral and thoracic/arch chimney grafts. Technical and clinical details and outcome were assessed., Results: The present review includes 831 patients who underwent EVAR/TEVAR (endovascular aneurysm repair/thoracic endovascular aneurysm repair) with one or more chimney, periscope, or sandwich grafts. For aortic visceral vessels 517 patients received 911 visceral CGs and 314 patients received 364 arch CGs. Most procedures (81% visceral and 69% arch CGs) were elective. Thirty day mortality was 4% for both groups. The rate of early EL-I was 13% (visceral CGs) and 11% (arch CGs). Most EL-I were handled conservatively (observation: 70% for visceral CG and 45% for arch CG). Early CG patency was high (97-99%) and remained high during follow up (median 17 months). Late (after 30 days) EL-I was reported in nine visceral (2%) and 12 arch (4%) CG cases. Few other late complications were reported, but those losing a kidney at the initial repair seemed to have a high risk of requiring permanent hemodialysis., Conclusion: Increasing amounts of data support the benefit of visceral and arch chimney graft techniques. In particular, the low early mortality and complication rates and high long-term patency seem advantageous; however, the majority of cases have been treated electively, and there is a high risk of bias in all studies. Mid- to long-term data suggest few late complications, except in cases where one renal artery was sacrificed. The CG technique is valuable for complex urgent patients and needs further documentation for other patient groups., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory angiopathy of unknown cause affecting medium-sized (most commonly renal) arteries and causing renovascular hypertension. The most common medial multifocal type of FMD (with the "string of beads" appearance) is more than four times more prevalent in females than in males. FMD accounts for up to 10% of cases of renovascular hypertension. Compared with patients with atherosclerotic renal artery stenosis, patients with FMD are younger, have fewer risk factors for atherosclerosis, and a lower occurrence of atherosclerosis in other vessels. The etiology is multifactorial, including vessel wall ischemia and smoking, as well as hormonal and genetic factors. Intra-arterial digital subtraction angiography is still the gold standard for exclusion or confirmation of renal artery stenosis caused by FMD, at least in young patients, who more often have lesions in branches of the renal artery. For FMD patients with atherosclerosis and those who are older (>50-55 years), significant renal artery stenosis may be confirmed or excluded with ultrasonography. The FMD lesion is typically truncal or distal, whereas atherosclerotic lesions are more often proximal or ostial. Treatment options are medical, endovascular (percutaneous transluminal renal angioplasty [PTRA]), and surgical. Invasive treatment should be considered when hypertension cannot be controlled with antihypertensive drugs and in patients with impaired renal function or ischemic nephropathy. PTRA has become the treatment of choice and normally yields good results, especially in unifocal disease and young patients. Pressure gradients are normally completely abolished, and there is no indication for stent placement. Surgical revascularization is indicated after PTRA complications; thrombosis, perforation, progressive dissection, repeated PTRA failure or restenosis. Centralization of handling is recommended.

Aims/hypothesis: Islet amyloid polypeptide (IAPP) is a beta cell hormone secreted together with insulin upon glucose stimulation. IAPP participates in normal glucose regulation, but IAPP is also known for its ability to misfold and form islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and deposited amyloid disrupts normal islet architecture. Even though IAPP and amyloid formation are much discussed in type 2 diabetes, our aim was to study the significance of IAPP in type 1 diabetes., Results: Plasma IAPP levels in children and adolescents with newly diagnosed type 1 diabetes (n = 224) were analysed and concentrations exceeding 100 pmol/L (127.2-888.7 pmol/L) were found in 11% (25/224). The IAPP increase did not correlate with C-peptide levels., Conclusions/interpretation: Plasma levels of IAPP and insulin deviate in a subpopulation of young with newly-diagnosed type 1 diabetes. The determined elevated levels of IAPP might increase the risk for IAPP misfolding and formation of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the list over putative pathological factors causing type 1 diabetes.

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.

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.

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).

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.

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., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Aim: Risk factors for development of peripheral arterial disease (PAD) are the same as for atherosclerotic coronary or precerebral disease, and patients with PAD have a high prevalence of concomitant atherosclerotic disease in coronary and precerebral arteries. However, these patients are still less likely to receive appropriate pharmacological secondary prevention than patients with coronary artery disease. The aim of this study was to evaluate the treatment of risk factors for patients undergoing open or endovascular surgery for PAD in our vascular department., Methods: We evaluated pharmacological treatment, lipid levels, blood pressures (BP), and smoking habits one month postoperatively in 953 patients (age [mean ± SD] 71±11 years, 524 [55%] men) undergoing open or endovascular surgical interventions for PAD., Results: We found that 89% of patients received statins and 98% received either platelet aggregation inhibitors or anticoagulants at the one month follow-up. Four hundred nineteen (70%) patients had achieved target level <4.5 mmol/L for s-total cholesterol, and 394 (67%) target level <2.5 mmol/L for s-LDL cholesterol. BP (mean ± SD) was 144±22/76±12 mmHg, systolic and diastolic target BPs (<140 mmHg and <90 mmHg, respectively) were achieved in 482 (51%) and 887 (95%) patients, respectively. The proportion of active smokers had been reduced from 41% preoperatively to 24% at the one month follow-up (P<0.0001)., Conclusion: Even though our practice has improved, there is still room for better follow-up of pharmacological risk factor treatment in PAD patients.

Aims/hypothesis: We studied the decline of C-peptide during the first year after diagnosis of Type 1 diabetes (T1D), and its relation to various factors., Methods: 3824/4017 newly diagnosed patients (95%) were classified as T1D in a national study. In a non-selected subgroup of 1669 T1D patients we determined non-fasting C-peptide both at diagnosis and after 1 year, and analyzed decline in relation to clinical symptoms and signs, initial C-peptide and occurrence of auto-antibodies., Results: Younger children lost more C-peptide (p<0.001) and the higher the C-peptide at diagnosis the larger the decline during the first year (p<0.0000). Patients with higher BMI had higher C-peptide at diagnosis but lost more (p<0.01), and those with lower HbA1c, without symptoms and signs at diagnosis, and with higher BMI, had higher C-peptide at diagnosis, but lost more during the first year (p<0.001). Finally, patients diagnosed during autumn had higher C-peptide at diagnosis, but lost more during the coming year (p<0.001). Occurrence of auto-antibodies did not correlate with C-peptide decline, except possibly for a more rapid loss in IAA-positive patients., Conclusions/interpretation: Even in a restricted geographical area and narrow age range (<18 years), the natural course of Type 1 diabetes is heterogeneous. This should be considered in clinical trials., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA)., Methods: We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA)., Results: ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 1-3 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (p < 0.0001). All three ZnT8A were associated with DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2)., Conclusions: Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer., (© 2012 John Wiley & Sons A/S.)

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., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: There are seasonal variations and gender differences in incidence of type 1 diabetes (T1D), metabolic control and responses to immune interventions at onset of the disease. We hypothesized that there are seasonal and gender differences in residual insulin secretion already at diagnosis of T1D., Methods: In 2005, a national study, the Better Diabetes Diagnosis, was started to classify all newly diagnosed children and adolescents with diabetes. About 95% (3824/4017) of the patients were classified as T1D, and our analyses are based on the patients with T1D., Results: C-peptide was lower in younger children, 0-10 years of age (0.23 ± 0.20 nmol/L) than in older children, 11-18 years of age (0.34 ± 0.28 nmol/L) (p < 0.000 ). There was a seasonal variation in non-fasting serum C-peptide, significantly correlated to the seasonal variation of diagnosis (p < 0.01). Most children were diagnosed in January, February and March as well as in October when C-peptide was highest, whereas fewer patients were diagnosed in April and May when serum C-peptide was significantly lower (p < 0.01). The seasonal variation of C-peptide was more pronounced in boys than in girls (p < 0.000 and p < 0.01, respectively). Girls had higher C-peptide than boys (p < 0.05), especially in early puberty., Conclusions: Both seasonal and gender differences in residual beta cell function exist already at diagnosis of T1D. These observations have consequences for treatment and for randomizing patients in immune intervention clinical trials., (Copyright © 2012 John Wiley & Sons, Ltd.)

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., (© 2012 John Wiley & Sons A/S.)

The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.

We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (≥1 islet autoantibody) type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.

Objectives: The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components., Background: It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis., Methods: The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (n(e) = 4,572); venous thromboembolism (n(e) = 4,607); intracranial aneurysm (n(e) = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588)., Results: LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 × 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 × 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 × 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 × 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 × 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15)., Conclusions: LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: The etiology of abdominal aortic aneurysm (AAA) includes inflammation, coagulation, and endothelial dysfunction. We have prospectively evaluated relations between these mechanisms and AAA growth. Tumour necrosis factor (TNF)-α, interleukin (IL)-6, endothelin (ET)-1, CD40 ligand and the complex formed between activated protein C (APC) and protein C inhibitor (PCI) were measured annually and related to AAA growth during up to 5 years in 206 patients with conservatively followed AAA., Methods: We evaluated 163 patients up to 1 year, 126 patients up to 2 years, 83 patients up to 3 years, 53 patients up to 4 years, and 33 patients up to 5 years. The total number of patient follow-up years was 458., Results: ET-1 remained unchanged except for a tendency to increase in the third and fourth years of follow-up. TNF-α decreased significantly during the first year and thereafter increased back to baseline values. There were no changes in IL-6, CD40 ligand, and APC-PCI complex. When patients in the highest and lowest quartiles of AAA growth up to 5 years follow-up were compared, APC-PCI complex levels tended to be higher (P=0.06) in the highest quartile of growth at three years (0.45 µg/l [i.q.r. 0.40-0.77] versus 0.28 µg/L [i.q.r. 0.14-0.36]). Δ-values of ET-1 and TNF-α did not show any correlation to growth. The 14 AAA patients that ruptured during follow-up did not differ from patients with non-ruptured AAA regarding biomarkers., Conclusion: In conclusion, none of the investigated mediators could be used to predict growth or rupture, or help to prolong intervals between ultrasound examinations in follow-up of AAA patients.

Aim: To determine the reliability of the disabled children's quality-of-life measure (DISABKIDS) chronic generic questionnaire and diabetes module in children. The questionnaire is being evaluated for repeated routine health-related quality-of-life (HrQoL) assessment and in association with the Swedish national paediatric diabetes registry (Swediabkids), which is a tool for regular clinical use., Methods: Children and parents completed the questionnaire during a routine visit to the diabetes clinic. In total, 120 families completed the test and retest. Split-half reliability correlation and intraclass correlation (ICC) coefficients were calculated. Bland & Altman plots were calculated on the generic HRQoL domain., Results: Both child and parent versions showed good internal consistency. Test-retest ICC coefficients for the generic HrQoL module were 0.913 for the children and 0.820 for the parent version. All generic domains independently showed good reliability. The diabetes module had a score of 0.855 for children and 0.823 for parents. Split-half correlation for generic and diabetes modules was 0.930 and 0.848 for children, 0.953 and 0.903 for parents. Bland and Altman plots showed substantial agreement between the two administrations for both children and parents., Conclusion: The DISABKIDS questionnaire is a reliable instrument for the repeated measurements of HrQoL in children with diabetes., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Objective: Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes human leukocyte antigen DQ (HLA-DQ) risk genotypes may be associated with increased body mass index (BMI)., Design: The type 1 diabetes high-risk HLA-DQ A1*05:01-B1*02:01/A1*03:01-B1*03:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by PCR and hybridization with allele-specific probes. BMI was determined after diabetes was stabilized., Subjects: A total of 2403 incident type 1 diabetes children below 18 years of age were ascertained in the Swedish national Better Diabetes Diagnosis (BDD) study between May 2005 to September 2009. All children classified with type 1 diabetes, including positivity for at least one islet autoantibody, were investigated., Results: Overall, type 1 diabetes HLA-DQ risk was negatively associated with BMI (P<0.0008). The proportion of the highest risk A1*05:01-B1*02:01/A1*03:01-B1)03:02 genotype decreased with increasing BMI (P<0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese (P<0.0001). Indeed, the proportion of patients with the low-risk A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype increased with increasing BMI (P<0.003). The magnitude of association on the multiplicative scale between the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and increased BMI was significant (P<0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% confidence interval 1.21-2.61; P<0.006). The increased proportion of overweight type 1 diabetes children with the A1*05:01-B1*02:01 haplotype was most pronounced in children diagnosed between 5 and 9 years of age., Conclusions: Susceptibility for childhood type 1 diabetes was unexpectedly found to be associated with the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and an increased BMI. These results support the hypothesis that overweight may contribute to the risk of type 1 diabetes in children positive for HLA-DQ A1*05:01-B1*02:01.

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.

Aim: To report C-peptide results in newly diagnosed patients and the relation to clinical diagnosis of diabetes., Methods: A nation-wide cohort, the Better Diabetes Diagnosis study was used to determine serum C-peptide at diagnosis in 2734 children and adolescents. Clinical data were collected at diagnosis and follow-up. C-peptide was determined in a validated and controlled time-resolved fluoroimmunoassay., Results: The clinical classification of diabetes, before any information on human leukocyte antigen, islet autoantibodies, or C-peptide was received, was type 1 diabetes (T1D) in 93%, type 2 diabetes (T2D) in 1.9%, maturity onset diabetes of the young (MODY) in 0.8%, secondary diabetes (0.6%), while 3.3% could not be classified. In a random, non-fasting serum sample at diagnosis, 56% of the patients had a C-peptide value >0.2 nmol/L. Children classified as T2D had the highest mean C-peptide (1.83 + 1.23 nmol/L) followed by MODY (1.04 ± 0.71 nmol/L) and T1D (0.28 ± 0.25 nmol/L). Only 1/1037 children who had C-peptide <0.2 nmol/L at diagnosis was classified with a type of diabetes other than T1D. Predictive value of C-peptide >1.0 nmol/L for the classification of either T2D or MODY was 0.46 [confidence interval 0.37-0.58]., Conclusions: More than half of children with newly diagnosed diabetes have clinically important residual beta-cell function. As the clinical diagnosis is not always straightforward, a random C-peptide taken at diagnosis may help to classify diabetes. There is an obvious use for C-peptide determinations to evaluate beta-cell function in children with diabetes., (© 2011 John Wiley & Sons A/S.)

Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD≤2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes., Methodology/principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, p<9.8×10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (p<0.002, p<0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas., Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.

Aim: Continuous glucose monitoring system (CGMS) provides detailed information on glucose fluctuations. The aim was to establish whether CGMS could be used during physical exercise and whether it detects more episodes of hypoglycaemia and hyperglycaemia than frequent blood glucose measurements., Methods: Adolescents with type 1 diabetes (12 girls and 47 boys) participated in three annual sports camps that lasted for 3-4 days and included different types of exercise: soccer, floorball + cross-country skiing and golf. During the study, blood glucose values, mean 8.7 ± 3.3 per day, were obtained with Hemocue in parallel with the CGMS., Results: Ninety-eight per cent of the participants used the sensor at all times during the camps. Eighty-seven per cent of the sensors gave adequate signals for 24 h and 66% for 48 h. Median durations of hypoglycaemia and hyperglycaemia were 1.7 h per day and 3.8 h per day, respectively. The CGMS identified significantly more episodes of hypoglycaemia (p < 0.005) and hyperglycaemia (p < 0.005) during the day and night than frequent blood glucose tests., Conclusion: We demonstrate that, even during days that included episodic strenuous physical exercise, CGMS could provide useful information on glucose fluctuations during day and night, albeit with significant failure rates., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Objective: Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type 1 diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged <2 and <5 years compared with population-based incidence studies and registries., Research Design and Methods: Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register)., Results: A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children <2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P < 0.0001; Swediabkids, P = 0.02; SEARCH, P < 0.0001; Finnish Register, P < 0.0001). The prevalence of DKA in TEDDY children diagnosed at <5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P < 0.0001) and the German DPV Register (32.2%) (P < 0.0001) but not compared with Swediabkids or the Finnish Register., Conclusions: Participation in the TEDDY study is associated with reduced risk of DKA at diagnosis of type 1 diabetes in young children.

Background and Aims: Autoantibodies against the zinc transporter 8 (ZnT8A) are common in type 1 diabetes (T1D). ZnT8A analyses are complicated by the fact that there are three variants of the autoantigen at amino acid position 325 representing ZnT8-R (Arginine), ZnT8-W (Tryptophan) and ZnT8-Q (Glutamin). The aims of the study were: 1) to develop an autoantigen triple mix Radio-Binding Assay (RBA) for ZnT8A; 2) to identify the individual ZnT8-R,-W,-QA reactivity and 3) to validate the triple mix ZnT8A RBA in children with newly diagnosed T1D., Methods: Serum samples were obtained from 2664 (56% males, n=1436) patients in the Swedish nationwide Better Diabetes Diagnosis (BDD) study representing patients with T1D (97%, n=2582), T2D (1.7%, n=46), MODY (1.0%, n=28) and secondary diabetes (0.3%, n=8). cDNA coding for the C-terminal end of each variant was prepared by site-directed mutagenesis and subcloned into a high efficiency in vitro transcription translation vector. The ZnT8 variants were labeled with 35S-methionine and used in a standard RBA separating free from autoantibody-bound autoantigen with Protein A-Sepharose., Results: ZnT8-TripleA was detected in 1678 (65%) patients with T1D, 4 (9%) T2D, 3 (11%) MODY and in none (0%) of the patients with secondary diabetes. Among the T1D patients ZnT8-RA was detected in 1351 (52%) patients, ZnT8-WA in 1209 (47%) and ZnT8-QA in 790 (31%) demonstrating that 1661 (64%) had one or several ZnT8A. The ZnT8-TripleA assay showed a false positive rate of 1.9% (n=49). Only 1.2% (n=32) of the T1D patients were false negative for ZnT8-TripleA compared to 0/46 (0%) of the T2D patients. The precision (intra assay CV) and reproducibility (inter assay CV) of the ZnT8-TripleA assay did not differ from the RBA of the individual ZnT8 variants., Conclusion: We conclude that the ZnT8-TripleA assay had low false positive and false negative rates. The ZnT8-TripleA assay would therefore be highly suitable not only to analyze patient with newly diagnosed diabetes but also for screening the general population since this assay demonstrated high sensitivity and very high specificity., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Introduction: Mer and Tyro3 are receptor tyrosine kinases important for the phagocytosis of apoptotic cells. Together with Axl, they constitute the TAM receptor family. These receptors can be shed from the cell membrane and their soluble extracellular regions can be found in plasma. The objective of this study was to elucidate whether the plasma levels of soluble Mer (sMer) and Tyro3 (sTyro3) were increased in systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), or critical limb ischemia (CLI)., Methods: ELISA kits were used to test plasma concentrations in controls and in patients with SLE, RA or CLI., Results: Increased levels of, in particular, sMer and, to some extent, sTyro3, were found in patients with SLE or RA, but not in patients with CLI. Patients with SLE demonstrated the highest sMer levels and there was a strong correlation to higher SLE disease activity score (SLEDAI). In contrast, in patients with RA, the sMer levels did not correlate with the disease activity score (DAS). In SLE, sMer levels were particularly high in those with lupus nephritis, patients who also had decreased C1q levels and increased titers of anti-DNA antibodies. After therapy, the plasma concentrations of sMer decreased in parallel to the decrease in SLEDAI score., Conclusions: The plasma concentrations of sMer and sTyro3 were significantly increased in patients with active SLE and RA, suggesting the TAM receptor shedding was affected by these autoimmune diseases. In particular, sMer was increased in SLE, the plasma levels of sMer reflecting disease activity.

Assessment of clinical risk factors for haemorrhagic complications in patients undergoing intra-arterial thrombolysis for lower limb ischaemia. Retrospective reviews of consecutive patients subjected to intra-arterial thrombolysis due to lower limb ischemia at the Vascular Center, Malmö University Hospital, during a 5-year period from 2001 to 2005. Two hundred and twenty intra-arterial thrombolytic procedures were carried out in 195 patients (46% women), median age 73 years. Haemorrhagic complications were recorded in 72 procedures (33%), of which 13 were discontinued. Haemorrhage at the introducer and distant sites occurred in 53 and 32 procedures, respectively. Thrombolysis for occluded synthetic grafts was associated with higher risk of haemorrhage (P = 0.043). The platelet count was lower (P = 0.017) and the dose of alteplas higher (P = 0.041) in bleeders than in non-bleeders. Age was not associated with haemorrhage (P = 0.30). Two patients died during thrombolysis, one of them due to intracerebral haemorrhage. The grade of thrombolysis was an independent predictor of both in-hospital amputation (P < 0.001; OR 3.5 [95% CI 2.1-5.8]) and mortality (P = 0.021; OR 3.0 [95% CI 1.2-7.9]). The in-hospital amputation-free survival rate was 85% (188/220). Haemorrhage associated with thrombolysis is common, but does seldom require discontinuation of treatment. Insertion of introducers for local thrombolysis through synthetic grafts, lower platelet count and higher alteplas dose were found to be risk factors for haemorrhage. An algorithm for clinical management of haemorrhage has been proposed.

Aims: To examine biomarkers of oxidative stress (oxs), and endothelin (ET)-1, in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) and to evaluate the effect of percutaneous transluminal renal angioplasty (PTRA)., Methods: Baseline measurements were made immediately before renal angiography in patients with suspected ARAS (significant ARAS, n = 83, and non-RAS, n = 59) and in 20 healthy, matched controls. In patients with ARAS, analyses were repeated 4 weeks after PTRA. All patients were treated with statins and acetylsalicylic acid throughout., Results: At baseline there were no significant differences between groups in biomarkers of oxs, whereas high-sensitivity C-reactive protein and blood leukocytes were significantly elevated in group ARAS versus both healthy controls and group non-RAS. Plasma levels of ET-1 and uric acid were significantly increased in group ARAS versus healthy controls prior to angiography and were significantly reduced compared to baseline 4 weeks after PTRA. PTRA had no significant effects on biomarkers of oxs, inflammation or serum creatinine concentrations., Conclusions: ARAS patients on treatment with antihypertensive agents, acetylsalicylic acid and statins showed elevated inflammatory indices but no increase in oxs. PTRA had no significant effects on inflammatory indices 4 weeks after intervention but reduced plasma ET-1 and uric acid., (Copyright © 2011 S. Karger AG, Basel.)

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., (© 2010 John Wiley & Sons A/S.)

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.

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.

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

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., (Copyright (c) 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Critical limb ischemia (CLI) is a severe peripheral arterial disease, characterized by rest pain, ulcers and gangrene in the legs. Gas6 is a vitamin K-dependent protein, which binds and activates the tyrosine kinase receptor Axl. Gas6-mediated Axl-signaling influences endothelial activation, neointima formation and immune regulation. Axl can be cleaved and soluble Axl (sAxl) is detectable in circulation., Design and Methods: We quantified plasma concentrations of Gas6 and sAxl in 189 CLI patients and 204 controls., Results: Gas6 and sAxl concentrations were increased in the CLI patients (p<0.0001) and correlated to C-reactive protein, interleukin-6, tumor necrosis factor alpha and neopterin. Patients who died within 3years of sampling (n=84) had increased concentrations of Gas6 and sAxl as compared to survivors (p=0.0009 and p=0.0011)., Conclusions: Plasma concentrations of Gas6 and sAxl correlate to inflammation and predict survival. This indicates that Gas6 and sAxl have a role in CLI, presumably connected to the inflammatory process., (Copyright 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Deep venous thrombosis (DVT) is much less common in the upper than in the lower extremity. Furthermore, there is limited information on risk factors for and the prognosis of upper extremity (UE)DVT in the general population., Aims: To estimate incidence, risk factors, and prognosis in UEDVT., Material and Methods: Among a total of 1203 patients with venous thromboembolism (VTE) diagnosed during 1998-2006 in the prospective population-based Malmö thrombophilia study, 63 (5%, 33 men [52%, age 54+/-17years], and 30 women [48%, age 55+/-22years]) had UEDVT and were evaluated concerning risk factors, treatment, recurrent VTE, and mortality., Results: At diagnosis, 19(30%) patients had known malignancy and 6(10%) had VTE heredity. Among female UEDVT patients 4(13%) used hormone therapy, 1(3%) was pregnant, while none was in the postpartum period. Of all 63 UEDVT patients, 12(19%) were heterozygous, and 3(5%) homozygous for the Factor V Leiden (FVL)-mutation. Two (3%) patients were heterozygous for the prothrombin mutation, and 1 patient (1.6%) showed both heterozygous FVL-mutation and lupus anticoagulant antibodies. Phlebography had been used for diagnosis in 48(76%), ultrasonography in 16(25%), and computer tomography (CT) in 9(14%) patients. Twenty-two patients (35%) were treated in hospital, and the remaining 41(65%) as out-patients. Sixty-two (98%) was treated with low molecular weight heparin (LMH), 60(95%) with oral anticoagulants (OAC), 3(5%) with unfractionated heparin, and 3(5%) with thrombolysis. VTE recurrence rate during median 62 (range 31-117) month of follow-up was 8/63(13%). Fifteen (24%) UEDVT patients died during follow-up; 9(47%) of the 19 patients with known malignancy at diagnosis and 6(14%) of the other patients. Yearly incidence of UEDVT was 3.6/100.000 (95% confidence interval [CI], 3.3 - 4.03)., Conclusion: Malignancies and the FVL mutation were common among patients with UEDVT. Mortality during follow-up vas high., (Copyright 2010 Elsevier Ltd. All rights reserved.)