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1.
Eur J Vasc Endovasc Surg ; 66(3): 397-406, 2023 09.
Article in English | MEDLINE | ID: mdl-37356704

ABSTRACT

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.


Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Prosthesis-Related Infections , Humans , Blood Vessel Prosthesis/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Conservative Treatment/adverse effects , Risk Factors , Retrospective Studies , Endovascular Procedures/adverse effects , Postoperative Complications/etiology , Prosthesis-Related Infections/surgery , Prosthesis-Related Infections/etiology , Treatment Outcome , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/complications
2.
Eur J Vasc Endovasc Surg ; 65(6): 778-786, 2023 06.
Article in English | MEDLINE | ID: mdl-36871924

ABSTRACT

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.


Subject(s)
Carotid Stenosis , Endarterectomy, Carotid , Stroke , Humans , Female , Male , Endarterectomy, Carotid/adverse effects , Risk Factors , Treatment Outcome , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Carotid Arteries , Stroke/epidemiology , Retrospective Studies , Risk Assessment , Stents
3.
Br J Surg ; 109(9): 846-856, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35848783

ABSTRACT

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.


Subject(s)
Intermittent Claudication , Nurse's Role , Follow-Up Studies , Humans , Intermittent Claudication/drug therapy , Intermittent Claudication/surgery , Lipids , Medication Adherence , Secondary Prevention
6.
Eur J Vasc Endovasc Surg ; 62(6): 918-926, 2021 12.
Article in English | MEDLINE | ID: mdl-34782231

ABSTRACT

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.


Subject(s)
Aorta, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis/adverse effects , Endovascular Procedures/adverse effects , Prosthesis-Related Infections/surgery , Aged , Aorta, Abdominal/diagnostic imaging , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/mortality , Endovascular Procedures/instrumentation , Endovascular Procedures/mortality , Female , Humans , Male , Middle Aged , Prosthesis-Related Infections/diagnostic imaging , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Registries , Reoperation , Retrospective Studies , Risk Assessment , Risk Factors , Sweden , Time Factors , Treatment Outcome
7.
Eur J Vasc Endovasc Surg ; 62(6): 927-934, 2021 12.
Article in English | MEDLINE | ID: mdl-34686449

ABSTRACT

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.


Subject(s)
Aorta, Abdominal/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis/adverse effects , Femoral Vein/surgery , Prosthesis-Related Infections/surgery , Aged , Anti-Infective Agents/administration & dosage , Aorta, Abdominal/diagnostic imaging , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Female , Humans , Male , Middle Aged , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Registries , Reoperation , Retrospective Studies , Risk Assessment , Risk Factors , Sweden , Time Factors , Treatment Outcome
8.
Eur J Vasc Endovasc Surg ; 62(3): 400-407, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34244093

ABSTRACT

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.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/surgery , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures , Intra-Abdominal Hypertension/etiology , Postoperative Complications/etiology , Adult , Aged , Aged, 80 and over , Balloon Occlusion , Case-Control Studies , Female , Humans , Intra-Abdominal Hypertension/diagnosis , Intra-Abdominal Hypertension/epidemiology , Logistic Models , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome
9.
Cancers (Basel) ; 13(10)2021 May 18.
Article in English | MEDLINE | ID: mdl-34070092

ABSTRACT

BACKGROUND: Cure proportion represents the proportion of patients who experience the same mortality rate as the general population and can be estimated together with the survival of the proportion experiencing excess mortality (the uncured). The aim was to estimate the cure proportions and survival among uncured stage II-III cutaneous melanoma (CM) patients. METHODS: 1- and 5-year relative survival ratios, cure proportions and the median survival times of uncured stage II-III CM patients in Sweden (n = 6466) were calculated based on data from the nationwide population-based Swedish Melanoma Register 2005-2013 with a follow-up through 2018. RESULTS: Stages IIB and IIC showed significant differences in standardized cure proportions vs. stage IIA CM (0.80 (95% CI 0.77-0.83) stage IIA; 0.62 (95% CI 0.59-0.66) stage IIB; 0.42 (95% CI 0.37-0.46) for stage IIC). Significant differences in standardized cure proportions were found for stages IIIB and IIIC-D CM vs. stage IIIA (0.76 (95% CI 0.68-0.84) stage IIIA; 0.52 (95% CI 0.45-0.59) stage IIIB; 0.35 (95% CI 0.30-0.39) for stage IIIC-D). CONCLUSIONS: The results are emphasizing the poor prognosis with low proportions cured by surgery only for sub-groups of stage II-III CM, specifically within stages IIB-C CM.

10.
N Engl J Med ; 383(26): 2538-2546, 2020 12 24.
Article in English | MEDLINE | ID: mdl-33296560

ABSTRACT

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.).


Subject(s)
Angioplasty, Balloon , Drug-Eluting Stents/adverse effects , Paclitaxel/administration & dosage , Peripheral Arterial Disease/therapy , Aged , Aged, 80 and over , Angioplasty, Balloon/adverse effects , Female , Follow-Up Studies , Humans , Ischemia/therapy , Male , Paclitaxel/adverse effects , Peripheral Arterial Disease/mortality , Proportional Hazards Models , Stents/adverse effects
12.
J Plast Reconstr Aesthet Surg ; 73(8): 1540-1546, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32467082

ABSTRACT

BACKGROUND: Completion lymph node dissection (CLND) for malignant melanoma is performed for regional cancer control and is associated with a high complication rate. It is unknown whether post-operative complications influence cancer recurrence or survival. Our aim was to evaluate the risk factors for short- and long-term complications after CLND, and to determine whether complications affect recurrence or survival. METHOD: We performed a retrospective cohort study including all melanoma patients who underwent CLND in the Stockholm region during 2005-2014. Patient and cancer characteristics were collected from medical records, as were clinical outcomes. Assessment was performed by multivariate logistic regression. RESULTS: Among 144 patients, the risk of any post-operative one year complication was 68.8%. Lymphedema (41.0%), infection (37.5 %), and seroma (31.3 %) were the most common complications. Diabetes and inguinal CLND were associated with nine- and ten-fold increased risks of post-operative complications (p<0.05), respectively. Complications were linked to an increased risk of recurrent cancer (p<0.05), median follow-up time of 49 months, but did not appear to affect five-year survival. CONCLUSION: Post-operative complications are common in melanoma patients undergoing CLND. Strong risk factors for complications are diabetes and inguinal CLND. Post-operative complications appear to be associated with increased risks of recurrent cancer, but the mechanism is unknown.


Subject(s)
Lymph Node Excision/statistics & numerical data , Melanoma/pathology , Melanoma/surgery , Postoperative Complications/epidemiology , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Adult , Aged , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Sentinel Lymph Node Biopsy , Sweden/epidemiology , Melanoma, Cutaneous Malignant
13.
Circ Res ; 126(5): 571-585, 2020 02 28.
Article in English | MEDLINE | ID: mdl-31893970

ABSTRACT

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.


Subject(s)
Myocytes, Smooth Muscle/metabolism , Proprotein Convertases/genetics , Serine Endopeptidases/genetics , Vascular Remodeling , Animals , Carotid Arteries/metabolism , Carotid Arteries/pathology , Cell Movement , Cell Proliferation , Cells, Cultured , Male , Matrix Metalloproteinases/genetics , Matrix Metalloproteinases/metabolism , Mice , Mice, Inbred C57BL , Myocytes, Smooth Muscle/physiology , Polymorphism, Single Nucleotide , Proprotein Convertases/metabolism , Proto-Oncogene Proteins c-sis/metabolism , Rats , Rats, Sprague-Dawley , Serine Endopeptidases/metabolism , Transcriptome
14.
Cardiovasc Res ; 116(2): 450-456, 2020 02 01.
Article in English | MEDLINE | ID: mdl-31135888

ABSTRACT

AIMS: To evaluate if ticagrelor, an effective platelet inhibitor without known non-responders, could inhibit growth of small abdominal aortic aneurysms (AAAs). METHODS AND RESULTS: In this multi-centre randomized controlled trial, double-blinded for ticagrelor and placebo, acetylic salicylic acid naïve patients with AAA and with a maximum aortic diameter 35-49 mm were included. The primary outcome was mean reduction in log-transformed AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12 months compared with baseline. Secondary outcomes include AAA-diameter growth rate and intraluminal thrombus (ILT) volume enlargement rate. A total of 144 patients from eight Swedish centres were randomized (72 in each group). MRI AAA volume increase was 9.1% for the ticagrelor group and 7.5% for the placebo group (P = 0.205) based on intention-to-treat analysis, and 8.5% vs. 7.4% in a per-protocol analysis (P = 0.372). MRI diameter change was 2.5 mm vs. 1.8 mm (P = 0.113), US diameter change 2.3 mm vs. 2.2 mm (P = 0.778), and ILT volume change 12.9% vs. 10.4% (P = 0.590). CONCLUSION: In this RCT, platelet inhibition with ticagrelor did not reduce growth of small AAAs. Whether the ILT has an important pathophysiological role for AAA growth cannot be determined based on this study due to the observed lack of thrombus modulating effect of ticagrelor. TRIAL REGISTRATION: The TicAAA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02070653.


Subject(s)
Aortic Aneurysm, Abdominal/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Thrombosis/prevention & control , Ticagrelor/therapeutic use , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Disease Progression , Double-Blind Method , Female , Hemorrhage/chemically induced , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Sweden , Thrombosis/diagnostic imaging , Thrombosis/etiology , Ticagrelor/adverse effects , Time Factors , Treatment Outcome
15.
JACC Basic Transl Sci ; 4(4): 480-494, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31468003

ABSTRACT

Human dendritic cells were differentiated from blood monocytes and treated with malondialdehyde (MDA) conjugated with human serum albumin (HSA). Autologous T cells from human plaques or blood were co-cultured with the pre-treated dendritic cells or treated directly. MDA modifications were studied by mass spectrometry. MDA-HSA induced a pro-inflammatory DC-mediated T-cell activation and also a strong direct effect on T cells, inhibited by an inhibitor of oxidative stress and antibodies against MDA. Atherogenic heat shock protein-60 was strongly induced in T cells activated by MDA-HSA. Two peptide modifications in atherosclerotic patients' HSA were similar to those present in in vitro MDA-modified HSA.

16.
Lancet ; 394(10197): 471-477, 2019 08 10.
Article in English | MEDLINE | ID: mdl-31280965

ABSTRACT

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.


Subject(s)
Lower Extremity/pathology , Melanoma/mortality , Melanoma/surgery , Skin Neoplasms/mortality , Skin Neoplasms/surgery , Torso/pathology , Upper Extremity/pathology , Aged , Denmark , Estonia , Female , Humans , Intention to Treat Analysis , Lower Extremity/surgery , Male , Margins of Excision , Melanoma/pathology , Middle Aged , Mortality , Norway , Skin Neoplasms/pathology , Survival Analysis , Sweden , Torso/surgery , Treatment Outcome , Upper Extremity/surgery , Melanoma, Cutaneous Malignant
18.
Eur J Vasc Endovasc Surg ; 57(2): 239-246, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30340857

ABSTRACT

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.


Subject(s)
Aneurysm, Infected/surgery , Aortic Aneurysm, Thoracic/microbiology , Aortic Rupture/microbiology , Endovascular Procedures/methods , Staphylococcal Infections/surgery , Aged , Aged, 80 and over , Aneurysm, Infected/epidemiology , Aortic Aneurysm, Thoracic/epidemiology , Aortic Aneurysm, Thoracic/surgery , Aortic Rupture/epidemiology , Aortic Rupture/surgery , Female , Humans , Male , Middle Aged , Registries , Reoperation/statistics & numerical data , Retrospective Studies , Staphylococcal Infections/epidemiology , Survival Analysis , Sweden/epidemiology , Treatment Outcome
19.
JACC Basic Transl Sci ; 3(4): 464-480, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30175270

ABSTRACT

Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.

20.
J Vasc Access ; 19(6): 535-541, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29614907

ABSTRACT

INTRODUCTION:: Thrombosis is one of the most common complications of dialysis vascular access and is a significant source of morbidity and healthcare-associated costs. In this retrospective study, outcomes for surgical thrombectomy and thrombolysis after access thrombosis in patients with arteriovenous fistulas or prosthetic grafts (arteriovenous grafts) were analysed. METHODS:: All patients with a primary episode of dialysis access thrombosis between 2005 and 2013 were included which yielded 131 patients with 149 episodes of access thrombosis (108 arteriovenous grafts; 41 arteriovenous fistulas). In all, 18 patients had two separate accesses during the study. Patient demographics, access anatomy, surgical and radiological procedural data were recorded. Kaplan-Meier estimates and Poisson regression were used for statistical analysis of access patency. RESULTS:: In total, 107 underwent surgical thrombectomy and 42 were treated with catheter-directed thrombolytic infusion. Technical success was 60% for surgical thrombectomy and 73% for thrombolysis (p = 0.18). There were no major complications and no deaths within 30 days of the procedure. More patients had adjunctive procedures in the thrombolysis group (65/107 vs 37/42; p = 0.002). There was an increasing risk of rethrombosis or a further access-related event for both arteriovenous fistulas and arteriovenous grafts after open thrombectomy compared with catheter-directed thrombolytic infusion, and arteriovenous fistulas exhibited a lower risk than arteriovenous grafts with an average increase in risk of 23.9% (95% confidence interval: 3.1-49) between each treatment group. CONCLUSION:: Thrombolysis for thrombosis of native and prosthetic dialysis accesses appears to yield better assisted primary patency compared to surgical thrombectomy. Our results suggest that thrombolysis may be considered the first-choice method for treating the thrombosed dialysis access.


Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Fibrinolytic Agents/administration & dosage , Graft Occlusion, Vascular/therapy , Renal Dialysis , Thrombectomy , Thrombolytic Therapy , Thrombosis/therapy , Adult , Aged , Aged, 80 and over , Female , Fibrinolytic Agents/adverse effects , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Infusions, Intravenous , Male , Middle Aged , Retrospective Studies , Sweden , Thrombectomy/adverse effects , Thrombolytic Therapy/adverse effects , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/physiopathology , Time Factors , Treatment Outcome , Vascular Patency/drug effects
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