Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.

BACKGROUND: The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease. METHODS: We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality. RESULTS: No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively). CONCLUSIONS: In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).

Long Term Mortality Rate in Patients Treated with Carotid Endarterectomy.

OBJECTIVE: Carotid endarterectomy (CEA) is an effective surgical method for stroke prevention in selected patients with carotid stenosis. Few contemporary studies report on the long term mortality rate in CEA treated patients, despite continuous changes in medication, diagnostics, and patient selection. Here, the long term mortality rate is described in a well characterised cohort of asymptomatic and symptomatic CEA patients, sex differences evaluated, and mortality ratio compared with the general population. METHODS: This was a two centre, non-randomised, observational study evaluating all cause, long term mortality in CEA patients from Stockholm, Sweden between 1998 and 2017. Death and comorbidities were extracted from national registries and medical records. Cox regression was adapted to analyse associations between clinical characteristics and outcome. Sex differences and standardised mortality ratio (SMR, age and sex matched) were studied. RESULTS: A total of 1 033 patients were followed for 6.6 ± 4.8 years. Of those, 349 patients died during follow up where the overall mortality rate was similar in asymptomatic and symptomatic patients (34.2% vs. 33.7%, p = .89). Symptomatic disease did not influence the mortality risk (adjusted HR 1.14, 95% CI 0.81 - 1.62). Women had lower crude mortality rate than men in the first 10 years (20.8% vs. 27.6%, p = .019). In women, cardiac disease was associated with increased mortality (adjusted HR 3.55, 95% CI 2.18 - 5.79), while in men, lipid lowering medication was protective (adjusted HR 0.61, 95% CI 0.39 - 0.96). Within the first five years after surgery, SMR was increased for all patients (men 1.50, 95% CI 1.21 - 1.86; women 2.41, 95% CI 1.74 - 3.35), as well as in patients < 80 years (SMR 1.46, 95% CI 1.23 - 1.73). CONCLUSION: Symptomatic and asymptomatic carotid patients have similar long term mortality rates after CEA, but men had worse outcome than women. Sex, age, and time after surgery were shown to influence SMR. These results highlight the need for targeted secondary prevention, to alter the long term adverse effects in CEA patients.

Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections.

OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort. METHODS: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality. RESULTS: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 - 1.5). CONCLUSION: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.

Effects of a person-centred, nurse-led follow-up programme on adherence to prescribed medication among patients surgically treated for intermittent claudication: randomized clinical trial.

BACKGROUND: Management of intermittent claudication should include secondary prevention to reduce the risk of cardiocerebrovascular disease. Patient adherence to secondary prevention is a challenge. The aim of this study was to investigate whether a person-centred, nurse-led follow-up programme could improve adherence to medication compared with standard care. METHODS: A non-blinded RCT was conducted at two vascular surgery centres in Sweden. Patients with intermittent claudication and scheduled for revascularization were randomized to the intervention or control (standard care) follow-up programme. The primary outcome, adherence to prescribed secondary preventive medication, was based on registry data on dispensed medication and self-reported intake of medication. Secondary outcomes were risk factors for cardiocerebrovascular disease according to the Framingham risk score. RESULTS: Some 214 patients were randomized and analysed on an intention-to-treat basis. The mean proportion of days covered (PDC) at 1 year for lipid-modifying agents was 79 per cent in the intervention and 82 per cent in the control group, whereas it was 92 versus 91 per cent for antiplatelet and/or anticoagulant agents. The groups did not differ in mean PDC (lipid-modifying P = 0.464; antiplatelets and/or anticoagulants P = 0.700) or in change in adherence over time. Self-reported adherence to prescribed medication was higher than registry-based adherence regardless of allocation or medication group (minimum P < 0.001, maximum P = 0.034). There was no difference in median Framingham risk score at 1 year between the groups. CONCLUSION: Compared with the standard follow-up programme, a person-centred, nurse-led follow-up programme did not improve adherence to secondary preventive medication. Adherence was overestimated when self-reported compared with registry-reported.

PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling.

RATIONALE: PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens. OBJECTIVE: Here, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall. METHODS AND RESULTS: Genetic analyses revealed association of intronic PCSK6 variant rs1531817 with maximum internal carotid intima-media thickness progression in high-cardiovascular risk subjects. This variant was linked with PCSK6 mRNA expression in healthy aortas and plaques but also with overall plaque SMA+ cell content and pericyte fraction. Increased PCSK6 expression was found in several independent human cohorts comparing atherosclerotic lesions versus healthy arteries, using transcriptomic and proteomic datasets. By immunohistochemistry, PCSK6 was localized to fibrous cap SMA+ cells and neovessels in plaques. In human, rat, and mouse intimal hyperplasia, PCSK6 was expressed by proliferating SMA+ cells and upregulated after 5 days in rat carotid balloon injury model, with positive correlation to PDGFB (platelet-derived growth factor subunit B) and MMP (matrix metalloprotease) 2/MMP14. Here, PCSK6 was shown to colocalize and cointeract with MMP2/MMP14 by in situ proximity ligation assay. Microarrays of carotid arteries from Pcsk6-/- versus control mice revealed suppression of contractile SMC markers, extracellular matrix remodeling enzymes, and cytokines/receptors. Pcsk6-/- mice showed reduced intimal hyperplasia response upon carotid ligation in vivo, accompanied by decreased MMP14 activation and impaired SMC outgrowth from aortic rings ex vivo. PCSK6 silencing in human SMCs in vitro leads to downregulation of contractile markers and increase in MMP2 expression. Conversely, PCSK6 overexpression increased PDGFBB (platelet-derived growth factor BB)-induced cell proliferation and particularly migration. CONCLUSIONS: PCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling. Visual Overview: An online visual overview is available for this article.

Risk Factors for Abdominal Compartment Syndrome After Endovascular Repair for Ruptured Abdominal Aortic Aneurysm: A Case Control Study.

OBJECTIVE: Ruptured abdominal aortic aneurysms (rAAA) are treated by endovascular aneurysm repair (rEVAR) increasingly often. Despite rEVAR being a minimally invasive method, abdominal compartment syndrome (ACS) remains a significant post-operative threat. The aim of this study was to investigate risk factors for ACS after rEVAR, including aortic morphological features. METHODS: The Swedish vascular registry (Swedvasc) was assessed for ACS after rEVAR in the period 2008 - 2015. All patients identified were compared with controls (i.e., patients who did not develop ACS after rEVAR), matched by centre and repair date. Case records were reviewed, and radiology images analysed in a core laboratory. Comparisons were performed with respect to physiological and radiological risk factors. RESULTS: The study population consisted of 40 patients with ACS and 68 controls. Pre-operatively, patients with ACS had a lower blood pressure (BP) than controls (median 70 mmHg vs. 97 mmHg; p < .001). Intra-operatively, they had aortic balloon occlusion more often (55.0% vs. 10.3%; p < .001) and received more transfusions than controls (median nine units of packed red blood cells [pRBC] vs. two units; p < .001). Ninety-seven per cent of those who developed ACS had a pre-operative BP < 70 mmHg, aortic balloon occlusion, or received more than five pRBC unit transfusions. Treatment outside the instructions for use did not differ between patients and controls (57.5% vs. 54.4%; p = .84), and neither did the pre-operative patency of the inferior mesenteric artery (57.1% vs. 63.9%; p = .52) nor the number of visible lumbar arteries on pre-operative imaging (2 vs. 4; p = .014). In multivariable logistic regression, the number of intra-operative transfusions were predictive of ACS (p < .001), while pre-operative hypotension (p = .32) and aortic balloon occlusion (p = .018) were not. CONCLUSION: ACS after rEVAR is mainly associated with physiological factors and is unlikely to develop without the presence of a pre-operative BP < 70 mmHg, the need for an aortic occlusion balloon, or more than five intra-operative pRBC unit transfusions. Treatment outside the IFU or any other morphological factor were not associated with a risk of ACS.

Deep Femoral Vein Reconstruction for Abdominal Aortic Graft Infections is Associated with Low Aneurysm Related Mortality and a High Rate of Permanent Discontinuation of Antimicrobial Treatment.

OBJECTIVE: Aortic prosthesis infection is a devastating complication of aortic surgery. In situ reconstruction with the neo-aorto-iliac system (NAIS) bypass technique has become increasingly used and is recommended in recent treatment guidelines. The main aim was to evaluate NAIS procedural outcomes when undertaken after previous open or endovascular aortic repair in Sweden. METHODS: In this retrospective study, The National Quality Registry for Vascular Surgery (Swedvasc) was used to identify Swedish centres that offered the NAIS bypass procedure for aortic prosthesis infection between 2008 and 2018. Variables of special interest were procedural details, short and long term survival, renal and other complications, and the durtion of antimicrobial treatment. RESULTS: Forty patients (36 males, four females [mean age 69 years], 32 open repairs, seven endovascular aortic repairs [EVAR] and one fenestrated EVAR; 21 presented with aorto-enteric fistula) operated on with NAIS bypass were reviewed. The median time from the primary aortic intervention to the NAIS bypass procedure was 32 months (range 0 - 252 months). Mean ± standard deviation operating time was 645 ± 160 minutes, mean blood loss was 6 277 ± 6 525 mL, mean length of intensive care unit stay was 5.3 ± 3.7 days, and mean length of overall hospital stay was 21.2 ± 11.4 days. Thirty-five patients (88%) had a positive microbial culture; the most commonly isolated pathogen was Candida spp. The majority of patients survived for 30 days (n = 35 [88%]), and 33 (83%) and 32 (80%) patients survived for 90 days and one year, respectively. The number of surviving patients free from antimicrobial treatment at 90 days, six months, and one year was 19 (58%), 29 (88%), and 30 (94%). After a mean long term follow up of 69.9 ± 44.7 months, 20 patients were still alive. CONCLUSION: The NAIS bypass procedure offered reasonable survival and functional outcomes, and was associated with a high cure rate, defined as freedom from any antimicrobial treatment.

Editor's Choice - Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study.

OBJECTIVE: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study. METHODS: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017. The primary aim was to compare short and long term survival, as well as complications for EAB and ISR. RESULTS: Some 126 radically surgically treated AGI patients were identified - 102 graft infections and 24 endograft infections - treated by EAB: 71 and ISR: 55 (23 neo-aorto-iliac systems, NAISs). No differences in early 30 day (EAB 81.7% vs. ISR 76.4%, p = .46), or long term five year survival (48.2% vs. 49.9%, p = .87) were identified. There was no survival difference comparing NAIS to other ISR strategies. The frequency of recurrent graft infection during follow up was similar: EAB 20.3% vs. ISR 17.0% (p = .56). Survival and re-infection rates of the new conduit did not differ between NAIS and other ISR strategies. Age ≥ 75 years (odds ratio [OR] 4.0, confidence interval [CI] 1.1 - 14.8), coronary artery disease (OR 4.2, CI 1.2 - 15.1) and post-operative circulatory complications (OR 5.2, CI 1.2 - 22.5) were associated with early death. Prolonged antimicrobial therapy (> 3 months) was associated with reduced long term mortality (HR 0.3, CI 0.1 - 0.9). CONCLUSION: In this nationwide multicentre study comparing outcomes of radically treated AGI, no differences in survival or re-infection rate could be identified comparing EAB and ISR.

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: long-term follow-up of a multicentre, randomised trial.

BACKGROUND: The optimal surgical excision margins are uncertain for patients with thick (>2 mm) localised cutaneous melanomas. In our previous report of this multicentre, randomised controlled trial, with a median follow-up of 6·7 years, we showed that a narrow excision margin (2 cm vs 4 cm) did not affect melanoma-specific nor overall survival. Here, we present extended follow-up of this cohort. METHODS: In this open-label, multicentre randomised controlled trial, we recruited patients from 53 hospitals in Sweden, Denmark, Estonia, and Norway. We enrolled clinically staged patients aged 75 years or younger diagnosed with localised cutaneous melanoma thicker than 2 mm, and with primary site on the trunk or upper or lower extremities. Patients were randomly allocated (1:1) to treatment either with a 2-cm or a 4-cm excision margin. A physician enrolled the patients after histological confirmation of a cutaneous melanoma thicker than 2 mm. Some patients were enrolled by a physician acting as responsible for clinical care and as a trial investigator (follow-up, data collection, and manuscript writing). In other cases physicians not involved in running the trial enrolled patients. Randomisation was done by telephone call to a randomisation office, by sealed envelope, or by computer generated lists using permuted blocks. Patients were stratified according to geographical region. No part of the trial was masked. The primary outcome in this extended follow-up study was overall survival and the co-primary outcome was melanoma-specific survival. All analyses were done on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT03638492. FINDINGS: Between Jan 22, 1992, and May 19, 2004, 936 clinically staged patients were recruited and randomly assigned to a 4-cm excision margin (n=465) or a 2-cm excision margin (n=471). At a median overall follow-up of 19·6 years (235 months, IQR 200-260), 621 deaths were reported-304 (49%) in the 2-cm group and 317 (51%) in the 4-cm group (unadjusted HR 0·98, 95% CI 0·83-1·14; p=0·75). 397 deaths were attributed to cutaneous melanoma-192 (48%) in the 2-cm excision margin group and 205 (52%) in the 4-cm excision margin group (unadjusted HR 0·95, 95% CI 0·78-1·16, p=0·61). INTERPRETATION: A 2-cm excision margin was safe for patients with thick (>2 mm) localised cutaneous melanoma at a follow-up of median 19·6 years. These findings support the use of 2-cm excision margins in current clinical practice. FUNDING: The Swedish Cancer Society, Stockholm Cancer Society, the Swedish Society for Medical Research, Radiumhemmet Research funds, Stockholm County Council, Wallström funds.

Nationwide Study on Treatment of Mycotic Thoracic Aortic Aneurysms.

OBJECTIVE: Mycotic aortic aneurysms are rare, life threatening, and complex. This nationwide study aimed to assess outcome after repair of mycotic thoracic aortic aneurysms (MTAAs). METHODS: Patients treated in Sweden for MTAAs between 2000 and 2016 were identified in the Swedish vascular registry (2010-16) and local patient registries (2000-09). Primary outcome was survival, and secondary outcomes included surgical strategy, rate of infection related complications (IRC), and re-operations. RESULTS: Fifty-two patients (median age 71 ± 8.1 years; 28 [54%] men, 13 [25%] ruptured) were identified (3.6% of all thoracic aortic aneurysm repairs in Sweden). Aneurysm location was aortic arch (n = 6; 11%), descending aorta (n = 42; 81%), and multiple locations (n = 4; 8%). Twenty-nine (56%) patients had positive cultures; the most prevalent agent was Staphylococcus aureus (n = 16; 31%). Operative techniques included thoracic endovascular aortic repair (TEVAR; n = 35 [67%]), fenestrated/branched TEVAR (n = 8; 15%), hybrid repair (n = 7; 14%), and open patch repair (n = 2; 4%). Survival was 92% (95% confidence interval [CI] 88-96) at 30 days, 88% (95% CI 84-93) at three months, 78% (73-84) at one year, and 71% (64-77) at five years. The mean follow up among survivors (> 90 days) was 45 months (range 4-216 months). Antibiotics were administered for a median of 15 weeks (range 0-220 weeks). IRCs occurred in nine patients (17%): sepsis (n = 3), graft infection (n = 3), recurrent mycotic aneurysm (n = 1), aorto-oesophageal/bronchial fistula (n = 2). Six (67%) IRCs were fatal; 80% occurred within the first year. Re-operations were performed in nine patients (17%). CONCLUSIONS: TEVAR was often used as treatment for MTAAs, with acceptable short- and long-term survival when compared with open cohorts in the literature. IRCs are of concern and warrant follow up and long-term antibiotic treatment.

Nationwide Study of the Treatment of Mycotic Abdominal Aortic Aneurysms Comparing Open and Endovascular Repair.

BACKGROUND: No reliable comparative data exist between open repair (OR) and endovascular aneurysm repair (EVAR) for mycotic abdominal aortic aneurysms (MAAAs). This nationwide study assessed outcomes after OR and EVAR for MAAA in a population-based cohort. METHODS: All patients treated for MAAAs in Sweden between 1994 and 2014 were identified in the Swedish vascular registry. The primary aim was to assess survival after MAAA with OR and EVAR. Secondary aims were analyses of the rate of recurrent infections and reoperations, and time trends in surgical treatment. Survival was analyzed using Kaplan-Meier and log-rank tests. A propensity score-weighted correction for risk factor differences in the 2 groups was performed, including the operation year to account for differences in treatment and outcomes over time. RESULTS: We identified 132 patients (0.6% of all operated abdominal aortic aneurysms in Sweden). Mean age was 70 years (standard deviation, 9.2), and 50 presented with rupture. Survival at 3 months was 86% (95% confidence interval, 80%-92%), at 1 year 79% (72%-86%), and at 5 years 59% (50%-68%). The preferred operative technique shifted from OR to EVAR after 2001 (proportion EVAR 1994-2000 0%, 2001-2007 58%, 2008-2014 60%). Open repair was performed in 62 patients (47%): aortic resection and extra-anatomic bypass (n=7), in situ reconstruction (n=50), and patch plasty (n=3); 2 patients died intraoperatively. EVAR was performed in 70 patients (53%): standard EVAR (n=55), fenestrated/branched EVAR (n=8), and visceral deviation with stent grafting (n=7); no deaths occurred intraoperatively. Survival at 3 months was lower for OR than for EVAR (74% versus 96%, P<0.001), with a similar trend present at 1 year (73% versus 84%, P=0.054). A propensity score-weighted risk-adjusted analysis confirmed the early better survival associated with EVAR. During median follow-up of 36 and 41 months for OR and EVAR, respectively, there was no difference in long-term survival (5 years 60% versus 58%, P=0.771), infection-related complications (18% versus 24%, P=0.439), or reoperation (21% versus 24%, P=0.650). CONCLUSION: This study demonstrates a paradigm shift in treatment of MAAA in Sweden, with EVAR being the preferred treatment modality. EVAR was associated with improved short-term survival in comparison with OR, without higher associated incidence of serious infection-related complications or reoperations.

Primary tumor sites in relation to ultraviolet radiation exposure and skin visibility correlate with survival in cutaneous melanoma.

The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976-2003 (n = 5,973). We followed the patients from date of diagnosis until death, emigration or December 31st 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors. We found that melanoma on chronic UVR exposure sites (face, dorsum of hands; adjusted HR 0.6; CI 0.4-0.7) and moderately intermittent UVR sites (lateral arms, lower legs, dorsum of feet; HR 0.7; CI 0.6-0.8) were associated with a favorable prognosis compared with highly intermittent sites (chest, back, neck, shoulders and thighs). Further, melanoma on poorly visible skin sites upon self-examination (scalp, retroauricular area, back, posterior upper arms and thighs, buttocks, pubic area; HR 1.3; CI 1.1-1.5) had a worse prognosis than those on easily visible sites (face, chest, abdomen, anterior upper arms and thighs, lower arms and legs, dorsum of hands and feet, palms). In conclusion, highly intermittent UVR exposure sites and poor skin visibility presumably correlate with reduced melanoma survival, independent of established tumor characteristics. A limitation of the study was the lack of information on actual individual UVR exposure.

Long-Term Outcome After Carotid Artery Stenting: A Population-Based Matched Cohort Study.

BACKGROUND AND PURPOSE: Long-term outcome after carotid artery stenting (CAS), a less invasive technique than carotid endarterectomy (CEA), for prevention of stroke, is unclear. The aim was to assess long-term outcomes after CAS, compared with CEA, in a nationwide cohort study. METHODS: All patients registered in the national Swedish Vascular Registry (Swedvasc) treated with primary CAS between 2005 and 2012 were identified. For every CAS, 2 CEA controls, matched for sex, age, procedure year, and indication (symtomatic/asymtomatic), were chosen. Postoperative stroke was identified by cross-matching the cohort with the InPatient Registry and charts review. Primary end point was ipsilateral stroke or death >30 days postoperatively. RESULTS: A total of 1157 patients were included, 409 CAS and 748 CEA; 73% men with mean age 70 years and 69% were symptomatic. Risk factor profile was similar between the 2 groups. Median follow-up time was 4.1 years. Ipsilateral stroke or death of >30 days postoperatively occurred in 95 of 394 in the CAS group versus 120 of 724 in the CEA group (adjusted hazard ratio, 1.59; 95% confidence interval, 1.15-2.18). The corresponding adjusted rates for death, ipsilateral stroke of >30 days, and any stroke or death of >30 days were 25.7% versus 18.6% (hazard ratio, 1.20; 95% confidence interval, 0.84-1.72), 9.4% versus 2.9% (hazard ratio, 3.40; 95% confidence interval, 1.53-7.53), 34.2% versus 23.6% (hazard ratio, 1.49; 95% confidence interval, 1.10-2.00) for the CAS group versus CEA group, respectively. CONCLUSIONS: In this nationwide cohort study, CAS was associated with an increased long-term risk of ipsilateral stroke and death during after the perioperative phase when compared with CEA.

Sentinel node location in trunk and extremity melanomas: uncommon or multiple lymph drainage does not affect survival.

BACKGROUND: Patients with cutaneous melanoma (CM) on the trunk have a worse prognosis than those with extremity CM. One reason could be multiple or uncommon (outside axilla or groin) sentinel node locations (SNLs). METHODS: We identified 859 patients who underwent sentinel node biopsy for trunk (n = 465) or extremity (n = 394) CM in three Swedish healthcare regions from 2000 to 2008. We collected patient, tumor, and sentinel node characteristics through clinical registers and medical records. We investigated the distribution of SNLs in a logistic regression model, and risk of overall and melanoma-specific death through 2011 in a multivariable Cox regression model. RESULTS: Trunk CM was associated with multiple SNLs (31 vs. 7 %; odds ratio [OR] 7.1; 95 % confidence interval [CI] 4.6-11.5; p < 0.001) but not uncommon SNLs (8 vs. 7 %; OR 1.1; 95 % CI 0.6-1.9; p = 0.75) compared with extremity CM. The increased risk of melanoma-specific death was confirmed for trunk CM (hazard ratio [HR] 1.9; 95 % CI 1.3-2.9; p = 0.003), especially on the upper back (HR 2.3; 95 % CI 1.4-3.6; p < 0.001) compared with extremity CM. Uncommon SNLs (HR 0.5; 95 % CI 0.2-1.4; p = 0.21) or multiple SNLs (HR 1.1; 95 % CI 0.4-2.9; p = 0.81) were not associated with melanoma-specific death compared with those with common/single SNL. CONCLUSIONS: Trunk melanomas were associated with multiple lymph drainage, but the worse prognosis of trunk melanomas could not be explained by the increased frequency of multiple or uncommon SNLs.

Profiling of atherosclerotic lesions by gene and tissue microarrays reveals PCSK6 as a novel protease in unstable carotid atherosclerosis.

OBJECTIVE: Carotid plaque instability is a major cause of ischemic stroke, but detailed knowledge about underlying molecular pathways is still lacking. Here, we evaluated large-scale transcriptomic and protein expression profiling in a biobank of carotid endarterectomies followed by characterization of identified candidates, as a platform for discovery of novel proteins differentially regulated in unstable carotid lesions. APPROACH AND RESULTS: Genes highly upregulated in symptomatic versus asymptomatic plaques were selected from Affymetrix microarray analyses (n=127 plaques), and tissue microarrays constructed from 34 lesions were assayed for 21 corresponding proteins by immunohistochemistry. Quantification of stainings demonstrated differential expression of CD36, CD137, and DOCK7 (P<0.05) in unstable versus stable lesions and the most significant upregulation of a proprotein convertase, PCSK6 (P<0.0001). Increased expression of PCSK6 in symptomatic lesions was verified by quantitative real-time polymerase chain reaction (n=233), and the protein was localized to smooth muscle α-actin positive cells and extracellular matrix of the fibrous cap by immunohistochemistry. PCSK6 expression positively correlated to genes associated with inflammation, matrix degradation, and mitogens in microarrays. Stimulation of human carotid smooth muscle cells in vitro with cytokines caused rapid induction of PCSK6 mRNA. CONCLUSIONS: Using a combination of transcriptomic and tissue microarray profiling, we demonstrate a novel approach to identify proteins differentially expressed in unstable carotid atherosclerosis. The proprotein convertase PCSK6 was detected at increased levels in the fibrous cap of symptomatic carotid plaques, possibly associated with key processes in plaque rupture such as inflammation and extracellular matrix remodeling. Further studies are needed to clarify the role of PCSK6 in atherosclerosis.

The role of procalcitonin in postimplantation syndrome after EVAR: a pilot study.

BACKGROUND: After endovascular aortic repair (EVAR) for treatment of aortoiliac aneurysms, patients commonly develop an inflammatory reaction: Postimplantation syndrome (PIS). Clinically, it may be hard to separate PIS from an infectious complication. Procalcitonin (PCT) is a diagnostic marker for severe bacterial infections and sepsis. We hypothesize that low-PCT levels facilitate the PIS diagnosis after EVAR. METHODS: Sixty-nine elective EVAR patients were included. Tympanic temperature, C-reactive protein (CRP), white blood cell count (WBC), and PCT were measured on days -1 and +1, +3 and +5. Complications, in-hospital stay, and infections were recorded. PIS was defined by a body temperature of ≥38°C and WBC ≥12,000/µL combined with no other detected complication or surgical event explaining the inflammatory response. Three cohort subgroups were compared: the noncomplication group, those with PIS, and the patients with complications or additional open surgical events. RESULTS: All patients developed various extents of postoperative inflammatory responses including a rise in WBC, CRP, and/or temperature. PIS was diagnosed in 12 patients. Forty patients had no complication and seventeen suffered complications or had an additional open surgical event. All PIS patients showed low-PCT levels. On day +3, in the PIS group, median PCT was 0.22 ng/mL (95% confidence interval [CI]: 0.15-0.28), WBC 13.2 × 10(9)/L (11.4-15.6), and CRP 196 mg/L (149-243). High PCT was observed in 6 patients, out of which 4 had complications or additional open surgical procedures. CONCLUSIONS: In patients with PIS after EVAR, there was a strong inflammatory reaction. In the PIS condition, PCT remains low. This pilot study shows that PCT may be useful for the PIS diagnosis.

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial.

BACKGROUND: Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin. METHODS: We undertook a randomised controlled trial in nine European centres. Patients with cutaneous melanoma thicker than 2 mm, at clinical stage IIA-C, were allocated to have either a 2-cm or a 4-cm surgical resection margin. Patients were randomised in a 1:1 allocation to one of the two groups and stratified by geographic region. Randomisation was done by sealed envelope or by computer generated lists with permuted blocks. Our primary endpoint was overall survival. The trial was not masked at any stage. Analyses were by intention to treat. Adverse events were not systematically recorded. The study is registered with ClinicalTrials.gov, number NCT01183936. FINDINGS: 936 patients were enrolled from Jan 22, 1992, to May 19, 2004; 465 were randomly allocated to treatment with a 2-cm resection margin, and 471 to receive treatment with a 4-cm resection margin. One patient in each group was lost to follow-up but included in the analysis. After a median follow-up of 6·7 years (IQR 4·3-9·5) 181 patients in the 2-cm margin group and 177 in the 4-cm group had died (hazard ratio 1·05, 95% CI 0·85-1·29; p=0.64). 5-year overall survival was 65% (95% CI 60-70) [corrected] in the 2-cm group and 65% (40-70) in the 4-cm group (p=0·69). INTERPRETATION: Our findings suggest that a 2-cm resection margin is sufficient and safe for patients with cutaneous melanoma thicker than 2 mm. FUNDING: Swedish Cancer Society and Stockholm Cancer Society.

Outcome after nitinol stenting in the superficial femoral and popliteal artery in an elderly population.

BACKGROUND: To assess outcomes in an elderly and diseased population after stenting in the femoropopliteal segment and evaluate risk factors for poor prognosis. METHODS: Retrospective study of femoropopliteal stents placed between March 2006 and January 2008. Patency was verified by duplex scanning. Risk factors associated with amputation or death and patency were analyzed using Cox regression. RESULTS: A total of 117 limbs in 112 patients were observed for a median of 18 months. Median age of the patients was 79 years; 68% were treated for critical limb ischemia and 85% had occlusive lesions. Mean lesion length was 15.4 cm (SD: 9.2) and mean stented length was 19.7 cm (standard deviation: 9.8). At 1 year, primary patency was 63%, primary-assisted patency was 67%, and secondary patency was 69%. Stent diameter ≤6 versus 7 mm was a risk factor for loss of patency with a hazard ratio (HR) of 2.9 (95% CI: 1.1-7.7). Significant risk factors for death or amputation were as follows: HR for rest pain versus claudication was 5.9 (1.1-32.8), HR for tissue loss versus claudication was 5.8 (1.1-29.6), HR for stent diameter ≤6 versus 7 mm was 3.6 (1.0-12.3), and HR for 3-4 stents versus 1-2 was 2.6 (1.1-6.1). CONCLUSION: Rutherford status is associated with death or amputation after stenting in the femoropopliteal segment. In addition, a smaller stent diameter and number of stents depict poorer prognosis independent of gender and anatomic level.