A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial.

BACKGROUND: Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. METHODS: Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. FINDINGS: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive). INTERPRETATION: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. FUNDING: UK National Institute of Health Research Health Technology Programme.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 Trial: Analysis of the Timing and Causes of Death in Participants Randomised to an Infrapopliteal Vein Bypass or Best Endovascular Treatment First Revascularisation Strategy.

OBJECTIVE: The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 trial enrolled participants with chronic limb threatening ischaemia who required an infrapopliteal, with or without a femoropopliteal, revascularisation procedure to restore limb perfusion. Participants randomised to a vein bypass (VB) first revascularisation strategy were over one third more likely than those randomised to a best endovascular treatment (BET) first revascularisation strategy to die from any cause during a median follow up of 40.0 (interquartile range 20.9, 60.6) months. The aim was to describe the timing and causes of death in BASIL-2 as a first step towards trying to better understand why randomisation to a VB first revascularisation strategy was associated with this excess mortality. METHODS: A 10 person international panel comprising vascular and endovascular surgeons as well as vascular interventional radiologists, who had all been principal investigators in BASIL-2, took part in a modified Delphi consensus exercise to adjudicate the primary cause of death and, in particular, whether the cause was primarily cardiac or non-cardiac. RESULTS: In 151/168 deaths (89.9%) the Delphi panel achieved a consensus regarding the cause of death being probably cardiac or non-cardiac. In the BET group, 16/77 deaths (21%) were classified as probably cardiac compared with 32/91 (35%) in the VB group (unadjusted subdistribution hazard ratio 2.16, 95% confidence interval [CI] 1.20 - 3.87; unadjusted cause specific hazard ratio 2.15, 95% CI 1.19 - 3.90). At the point of randomisation, 64/344 (18.6%), 37/344 (10.8%), and 40/342 (9%) participants had a previous myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG), respectively. There was no evidence of varying treatment effects for cause of death in subgroup analyses of previous PCI, CABG, or MI. CONCLUSION: The excess mortality observed in the VB first revascularisation strategy group in BASIL-2 was largely due to deaths that were adjudicated by the Delphi panel as probably primarily cardiac. These excess cardiac deaths were observed throughout follow up and there was no evidence of non-proportional hazards. Further work is ongoing to try to better understand the reasons for these findings.

Impact of injury mechanism on early wound closure in patients with acute conflict-related extremity wounds: A prospective cohort analysis from two civilian hospitals in Iraq and Jordan.

BACKGROUND: Gunshots and bomb blasts are important causes of extremity injuries in conflict zones, yet little research exists on the characteristics and outcomes of these injuries in civilian populations. METHODS: We performed a prospective cohort analysis utilizing data from a randomized trial conducted at two civilian hospitals in Jordan and Iraq in 2015-2019. Adults who presented ≤72 h of sustaining an extremity injury were included. We used mechanism of injury (gunshot/bomb blast) as the exposure and wound closure by day 5 as the primary outcome measure. RESULTS: The population predominantly comprised young men (n = 163, 94% male, and median age 29 years) injured by gunshots (61%) or bomb blasts (39%). Compared with the gunshot group, more participants in the bomb blast group had concomitant injuries (32/63 [51%] vs. 11/100 [11%], p < 0.001) and vascular injuries (9/63 [14%] vs. 4/100 [4%], p = 0.02). The wounds were larger in the bomb blast group compared with the gunshot group (median area 86 cm2 [IQR 24-161] vs. 21 cm2 [IQR 7-57], p < 0.001). Compared with the bomb blast group, significantly more participants in the gunshot group achieved wound closure by day 5 (74/100 [74%] vs. 16/63 [25%], p < 0.001). This difference remained after controlling for confounding factors (odds ratio 4.7, 95% confidence interval 1.6-13.7). CONCLUSIONS: In civilians with conflict-related extremity injuries, bomb blast wounds had a lower likelihood of achieving closure within 5 days than gunshot wounds, independent of other factors, such as wound size and vascular injuries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02444598. Registered 14-05-2015, https://classic. CLINICALTRIALS: gov/ct2/show/NCT02444598.

Risk factors for reamputations in patients amputated after revascularization for critical limb-threatening ischemia.

OBJECTIVE: Despite vascular intervention, patients with critical limb-threatening ischemia (CLTI) have a high risk of amputation. Furthermore, this group has a high risk for stump complications and reamputation. The primary aim of this study was to identify risk factors predicting reamputation after a major lower limb amputation in patients revascularized because of CLTI. The secondary aim was to investigate mortality after major lower limb amputation. METHODS: There were 288 patients who underwent a major ipsilateral amputation after revascularization because of CLTI in Stockholm, Sweden, during 2007 to 2013. The main outcome was ipsilateral reamputation. RESULTS: Of 288 patients, 50 patients had a reamputation and 222 died during the 11-year follow-up. Patients with ischemic pain as an indication for primary amputation had nearly four times higher risk for a reamputation compared with those with a nonhealing ulcer (subdistribution hazard ratio, 3.55; confidence interval, 1.55-8.17). Higher age was associated with an increased risk for death in the multivariable analysis (hazard ratio, 1.03; confidence interval, 1.02-1.04). CONCLUSIONS: Patients with ischemic pain as an indication for amputation have an elevated risk of reamputation. Ischemic pain may be indicative of a more extensive and proximal ischemia compared with patients with foot tissue loss. An extended evaluation of the preoperative circulation before amputation may facilitate the choice of amputation level and could lead to a reduction of reamputations.

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.

Risk factors for amputation are influenced by competing risk of death in patients with critical limb ischemia.

OBJECTIVE: Patients with critical limb ischemia (CLI) have a high risk of amputation and death. Death is a competing risk that affects the estimated amputation risk. Our aim was to find the specific risk factors for amputation for patients with CLI using competing risk analyses and compared these results with those from standard Cox regression analysis. METHODS: Patients who had undergone revascularization for CLI (2009-2013, with follow-up data until 2017) in Stockholm were identified from the Swedish National Registry for Vascular Surgery. The main outcome was major amputation. The risk factors for amputation were assessed using competing risk analysis and compared with the risk factors for amputation-free survival identified using Cox proportional hazards regression analysis. RESULTS: Of 855 patients with CLI, 178 had required a major amputation and 415 had died during the 8-year follow-up period. In the competing risk regression, age (subdistribution hazard ratio [sub-HR], 0.98; 95% confidence interval [CI], 0.97-1.00), ambulatory status (independent vs bedridden; sub-HR, 4.10; 95% CI, 2.14-7.86), and ischemic wound vs rest pain (sub-HR, 3.03; 95% CI, 1.72-5.36) were associated with amputation, considering death as a competing risk. In contrast, Cox regression analysis identified female vs male (hazard ratio [HR], 0.77; 95% CI, 0.64-0.94), age (HR, 1.02; 95% CI, 1.01-1.03), renal impairment (HR, 2.08; 95% CI, 1.61-2.67), ambulatory status (independent vs bedridden; HR, 3.45; 95% CI, 2.30-5.18), and ischemic wound vs rest pain (HR, 2.41; 95% CI, 1.78-3.25) as risk factors. CONCLUSIONS: The risk factors associated with amputation differed when analyzing the data using competing risk regression vs Cox regression. The differences between the analyses indicated that a risk exists for biased estimates using standard survival methods when a strong competing risk such as death is present.

Infection with high proportion of multidrug-resistant bacteria in conflict-related injuries is associated with poor outcomes and excess resource consumption: a cohort study of Syrian patients treated in Jordan.

BACKGROUND: Armed conflicts are a major contributor to injury and death globally. Conflict-related injuries are associated with a high risk of wound infection, but it is unknown to what extent infection directly relates to sustainment of life and restoration of function. The aim of this study was to investigate the outcome and resource consumption among civilians receiving acute surgical treatment due to conflict-related injuries. Patients with and without wound infections were compared. METHODS: We performed a cohort study using routinely collected data from 457 consecutive Syrian civilians that received surgical treatment for acute conflict-related injuries during 2014-2016 at a Jordanian hospital supported by Médecins Sans Frontières. We defined wound infection as clinical signs of infection verified by a positive culture. We used logistic regression models to evaluate infection-related differences in outcome and resource consumption. RESULTS: Wound infection was verified in 49/457 (11%) patients. Multidrug-resistance (MDR) was detected in 36/49 (73%) of patients with infection. Among patients with infection, 11/49 (22%) were amputated, compared to 37/408 (9%) without infection, crude relative risk = 2.62 (95% confidence interval 1.42-4.81). Infected patients needed 12 surgeries on average, compared to five in non-infected patients (p < .00001). Mean length of stay was 77 days for patients with infection, and 35 days for patients without infection (p = .000001). CONCLUSIONS: Among Syrian civilians, infected conflict-related wounds had a high prevalence of MDR bacteria. Wound infection was associated with poor outcomes and high resource consumption. These results could guide the development of antibiotic protocols and adaptations of surgical management to improve care for wound infections in conflict-related injuries. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02744144 ). Registered April 13, 2016. Retrospectively registered.

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.

The receptor for advanced glycation end products and risk of peripheral arterial disease, amputation or death in type 2 diabetes: a population-based cohort study.

BACKGROUND: Patients with type 2 diabetes have a high risk for early and extensive development of peripheral arterial disease (PAD) and this excess risk is not explained by increased burden of traditional atherosclerotic risk factors. Activation of the receptor for advanced glycation end products (RAGE) could be one additional mechanism for accelerated PAD and increased risk for amputation and death. We investigated the association between RAGE plasma components and the risk for PAD, amputation and death in patients with type 2 diabetes. We also estimated the rate of amputation-free survival and survival without PAD. METHODS: We investigated if plasma levels of carboxymethyl-lysine, S100A12 and endosecretory RAGE (esRAGE) were associated with two endpoints: survival without development of PAD and survival without amputation in a 12 years prospective population-based cohort of 146 patients with type 2 diabetes, free from PAD at inclusion. Influence of baseline plasma levels of RAGE ligands (individually and combined by a RAGE-score) were evaluated for both endpoints in the Cox-regression analysis. RESULTS: 106 patients survived without amputation and 93 survived without signs of PAD during follow up. Higher levels of S100A12 and RAGE-score were associated with increased risk for amputation or death, hazard ratios (HR) 1.29; 95% confidence interval (CI) [1.04, 1.59] and 1.79; 95% CI [1.07, 2.99] and with increased risk for PAD or death, HR 1.22; 95% CI [1.00, 1.49] and 1.56; [1.00, 2.44] after adjustment for age and sex. The effect was decreased after adjustment for Framingham cardiovascular disease score: risk for amputation or death, HR 1.17; 95% CI [0.94, 1.46] and 1.54; [0.95, 2.49], and risk for PAD or death, HR 1.12; 95% CI [0.91, 1.38] and 1.38; [0.91, 2.11] for S100A12 and RAGE-score respectively. The incidence for amputation or death was 2.8 per 100 person-years; 95% CI [2.0, 3.7] and the incidence rate for PAD or death was 3.6 per 100 person-years; 95% CI [2.7, 4.8]. CONCLUSION: Higher plasma levels of S100A12 and the combined effect (RAGE-score) of esRAGE, carboxymethyl-lysine and S100A12 seem to be associated with shorter PAD- and amputation-free survival in patients with type 2 diabetes. This may indicate a role for S100A12 in PAD by activation of the RAGE system.

Wound specific quality of life after blast or gunshot injury: Validation of the wound QoL instrument.

BACKGROUND: Acute blast or gunshot wounds have a negative effect on the patients' health related quality of life (HRQoL). No validated instrument exists to assess the HRQoL of patients with such wounds. Therefore, we aimed to test and validate a subscale of an existing HRQoL instrument among patients with acute blast or gunshot wounds. METHODS: We used data from a randomized controlled trial comparing negative pressure wound therapy with standard treatment of civilian adults with acute extremity blast or gunshot wounds. We evaluated the reliability (internal consistency, stability) and validity of the body subscale of the Wound QoL instrument using the World Health Organisation 20 question self-reporting questionnaire as gold standard. RESULTS: A total of 152 participants were included in the study. The participants were predominantly (93.4%) male, and median age was 29.0 years (IQR 21.0-34.0). The internal consistency was acceptable while a test-retest analysis indicated instability in the Wound QoL instrument. The content validity of the instrument was considered satisfactory; however, the criterion validity was found to be insufficient. CONCLUSIONS: Our results indicate that Wound QoL is a promising instrument for the assessment of wound specific HRQoL among patients with acute blast or gunshot wounds. Further testing and validation is needed.

Health-related quality of life and prosthesis use among patients amputated due to peripheral arterial disease - a one-year follow-up.

PURPOSE: A major amputation affects the patients' independence, well-being and HRQoL. However, prosthesis use and the impact on the patient's HRQoL are scarcely described. The aim was to compare HRQoL between walker and non-walker amputees. Secondary aim was to evaluate prosthesis use and habits. METHOD: Ninety-eight patients with a major amputation due to peripheral arterial disease were included during 2014-2018. They were interviewed using EQ-5D-3L (HRQoL), Stanmore Harold Wood mobility grade (prosthesis use) and Houghton scale (prosthesis habits). RESULTS: Seventy-three patients completed the one-year follow-up, out of them 56 got a prosthesis. Twenty-three used it to walk both inside and outside. EQ-5D-3L at follow-up was increased in all patients in comparison to baseline (0.16 versus 0.59, p < 0.001). Patients walking with prosthesis had the largest improvement (0.12 versus 0.78, p < 0.001). A sub-analysis aiming to study the importance of independent movement showed an improved HRQoL at follow-up among those classified as prosthesis-user (p<0.001) and walker (p<0.001), but not among non-prosthesis users (p = 0.245). CONCLUSION: Learning how to use, not exclusively to walk with, a prosthesis after an amputation is important for the patients' HRQoL. At follow-up, patients using their prosthesis to walk or to move to a wheelchair, showed an improved HRQoL compared to baseline.IMPLICATIONS FOR REHABILITATION Walking ability with a prosthesis is important for the patient's perceived HRQoL after an amputation.Rehabilitation of amputees should focus on independence and movability and not only on walking ability.Wider use of prescribing prostheses after an amputation also to those predicted as non-walkers, may increase the number of patients with independence and improved HRQoL.When using their prosthesis for independent movement, patients who were otherwise unable to walk due to their amputation were able to achieve HRQoL comparable to walking amputees.

Cost analysis of negative-pressure wound therapy versus standard treatment of acute conflict-related extremity wounds within a randomized controlled trial.

BACKGROUND: Clinical outcomes after negative-pressure wound therapy (NPWT) and standard treatment of conflict-related extremity wounds are similar. In resource-limited settings, cost affects the choice of treatment. We aimed to estimate treatment-related costs of NPWT in comparison with standard treatment for conflict-related extremity wounds. METHODS: We derived outcome data from a randomized, controlled superiority trial that enrolled adult (≥ 18 years) patients with acute (≤ 72 h) conflict-related extremity wounds at two civilian hospitals in Jordan and Iraq. Primary endpoint was mean treatment-related healthcare costs (adjusted to 2019 US dollars). RESULTS: Patients were enrolled from June 9, 2015, to October 24, 2018. A total of 165 patients (155 men [93.9%]; 10 women [6.1%]; and median [IQR] age, 28 [21-34] years) were included in the analysis. The cost per patient treated with NPWT was $142 above that of standard treatment. Overall, results were robust in a sensitivity analysis. CONCLUSIONS: With similar clinical outcomes compared to standard care, our results do not support the use of NPWT in routine treatment of conflict-related extremity wounds at civilian hospitals in resource scarce settings. Trial registration NCT02444598.

Negative pressure wound therapy versus standard treatment in patients with acute conflict-related extremity wounds: a pragmatic, multisite, randomised controlled trial.

BACKGROUND: In armed conflict, injuries among civilians are usually complex and commonly affect the extremities. Negative pressure wound therapy (NPWT) is an alternative to standard treatment of acute conflict-related extremity wounds. We aimed to compare the safety and effectiveness of NPWT with that of standard treatment. METHODS: In this pragmatic, randomised, controlled superiority trial done at two civilian hospitals in Jordan and Iraq, we recruited patients aged 18 years or older, presenting with a conflict-related extremity wound within 72 h after injury. Participants were assigned (1:1) to receive either NPWT or standard treatment. We used a predefined, computer-generated randomisation list with three block sizes. Participants and their treating physicians were not masked to treatment allocation. The primary endpoint was wound closure by day 5. The coprimary endpoint was net clinical benefit, defined as a composite of wound closure by day 5 and freedom from any bleeding, wound infection, sepsis, or amputation of the index limb. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02444598, and is closed to accrual. FINDINGS: Between June 9, 2015, and Oct 24, 2018, 174 patients were randomly assigned to either the NPWT group (n=88) or the standard treatment group (n=86). Five patients in the NPWT group and four in the standard treatment group were excluded from the intention-to-treat analysis. By day 5, 41 (49%) of 83 participants in the NPWT group and 49 (60%) of 82 participants in the standard treatment group had closed wounds, with an absolute difference of 10 percentage points (95% CI -5 to 25, p=0·212; risk ratio [RR] 0·83, 95% CI 0·62 to 1·09). Net clinical benefit was seen in 33 (41%) of 81 participants in the NPWT group and 34 (44%) of 78 participants in the standard treatment group, with an absolute difference of 3 percentage points (95% CI -12 to 18, p=0·750; RR 0·93, 95% CI 0·65 to 1·35). There was one in-hospital death in the standard treatment group and none in the NPWT group. The proportion of participants with sepsis, bleeding leading to blood transfusion, and limb amputation did not differ between groups. INTERPRETATION: NPWT did not yield superior clinical outcomes compared with standard treatment for acute conflict-related extremity wounds. The results of this study not only question the use of NPWT, but also question the tendency for new and costly treatments to be introduced into resource-limited conflict settings without supporting evidence for their effectiveness. This study shows that high-quality, randomised trials in challenging settings are possible, and our findings support the call for further research that will generate context-specific evidence. FUNDING: The Stockholm County Council, the Swedish National Board of Health and Welfare, and Médecins Sans Frontières.

Aortic dissection in pregnancy: a life-threatening disease and a diagnosis of worth considering.

Acute aortic dissection is a life-threatening disease. To increase the awareness of this diagnosis as a cause of feto-maternal mortality during pregnancy, we have analyzed risk factors using information from five pregnant women admitted for acute aortic dissection to the Karolinska University Hospital over an eight-year period (1999-2007). Four of the women died and only one survived. One fetus was stillborn and all newborn infants showed signs of asphyxia at birth. Of the women, who were on average five years above the mean age for delivery in Sweden, three had hypertension, two had first-degree relatives with aortic dissection which had occurred during the second half of pregnancy (gestational age at diagnosis 26-41 weeks). The most common presenting symptoms were severe back, abdominal and leg pain, and confusion. If a rapid diagnosis is not made, the risk of mortality for both mother and fetus is high. The incidence of aortic rupture during pregnancy in Sweden appears to be 14.5/1,000,000 and the case maternal fatality ratio 4.4/1,000,000.

High 18F-FDG Uptake in synthetic aortic vascular grafts on PET/CT in symptomatic and asymptomatic patients.

UNLABELLED: Graft infection is a serious complication to vascular surgery. The aim of this study was to assess (18)F-FDG uptake in vascular grafts in patients with or without symptoms of graft infection. METHODS: In all 2,045 patients examined by PET/CT at our clinic, 16 patients with synthetic aortic grafts were identified and reevaluated for (18)F-FDG accumulation. Clinical and biochemical data were obtained from patient records. RESULTS: High (18)F-FDG uptake was found in 10 of 12 grafts in the patients who underwent open surgery and in 1 of 4 grafts in patients who underwent endovascular aneurysm repair. On the basis of biochemical and clinical data, it was concluded that 1 of the 16 patients had a graft infection at the time of investigation. CONCLUSION: (18)F-FDG uptake in vascular grafts was found in the vast majority of patients without graft infection. The risk of a false-positive diagnosis of graft infection by (18)F-FDG PET/CT is evident.

Outcomes of endovascular abdominal aortic aneurysm repair compared with open surgical repair in high-risk patients: results from the Swedish Vascular Registry.

BACKGROUND: The management of infrarenal aortic aneurysms in high-risk patients remains a challenge. Endovascular aneurysm repair (EVAR) is associated with superior short-term mortality rates but unclear long-term results and has not been shown to improve survival in patients unfit for open repair (OR). The aim of this population-based study was to evaluate the outcome after elective EVAR compared with OR in a high-risk patient cohort. METHODS: Prospectively collected data from January 2000 to December 2006 were retrieved from the Swedish Vascular Registry. The high-risk cohort was defined as age >or=60 years, American Anesthesiologists Association (ASA) class 3 or 4, and at least one cardiac, pulmonary, or renal comorbidity. These criteria were met by 217 of 1000 EVAR patients and 483 of 2831 OR patients. Primary end points were 30-day and 1-year all-cause mortality. Kaplan-Meier curves for survival and multivariate Cox regression analyses were performed. RESULTS: The crude 30-day and 1-year all-cause mortality rates for EVAR vs OR for the whole treatment group (n = 3831) were 1.8% vs 2.8% and 8.0% vs 7.2%, respectively. In the high-risk cohort (n = 700), EVAR patients were approximately 2 years older and renal insufficiency and diabetes mellitus were more common, and smoking was more prevalent in the OR group. About two-thirds of EVAR procedures were performed at university hospitals and one-half of OR procedures were performed at county hospitals. In the high-risk cohort, there was no difference in mortality at 30-days (EVAR, 4.6% vs OR, 3.3%), but OR had lower 1-year mortality (8.5% vs 15.9%; P = .003). More bleeding complications occurred in the EVAR group, but more pulmonary complications occurred in the OR group; however, there was no difference in cardiac, cerebrovascular, or renal complications. The mean follow-up was 3.4 years. EVAR was associated with increased mortality risk after adjusting for age, ASA class, and comorbidities (hazard ratio, 1.50; 95% confidence interval, 1.07-2.12; P = .02). Kaplan-Meier survival analysis showed a lower mortality rate for patients undergoing OR, which remained during follow-up (P = .001). CONCLUSIONS: Elective OR of aortic aneurysms seems to have a better outcome compared with EVAR in this specific, population-based, high-risk patient cohort after adjusting for covariates. We cannot confirm the benefit of EVAR from previous registry studies with a similar high-risk definition. In clinical practice, OR may be at least as good as EVAR in high-risk patients fit for surgery.

Negative-Pressure Wound Therapy Versus Standard Treatment of Adult Patients With Conflict-Related Extremity Wounds: Protocol for a Randomized Controlled Trial.

BACKGROUND: In armed conflict, injuries commonly affect the extremities and contamination with foreign material often increases the risk of infection. The use of negative-pressure wound therapy has been described in the treatment of acute conflict-related wounds, but reports are retrospective and with limited follow-up. OBJECTIVE: The objective of this study is to investigate the effectiveness and safety of negative-pressure wound therapy use in the treatment of patients with conflict-related extremity wounds. METHODS: This is a multisite, superiority, pragmatic randomized controlled trial. We are considering for inclusion patients 18 years of age and older who are presenting with a conflict-related extremity wound within 72 hours after injury. Patients are block randomly assigned to either negative-pressure wound therapy or standard treatment in a 1:1 ratio. The primary end point is wound closure by day 5. Secondary end points include length of stay, wound infection, sepsis, wound complications, death, and health-related quality of life. We will explore economic outcomes, including direct health care costs and cost effectiveness, in a substudy. Data are collected at baseline and at each dressing change, and participants are followed for up to 3 months. We will base the primary statistical analysis on intention-to-treat. RESULTS: The trial is ongoing. Patient enrollment started in June 2015. We expect to publish findings from the trial by the end of 2019. CONCLUSIONS: To the best of our knowledge, there has been no randomized trial of negative-pressure wound therapy in this context. We expect that our findings will increase the knowledge to establish best-treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02444598; http://clinicaltrials.gov/ct2/show/NCT02444598 (Archived by WebCite at http://www.webcitation.org/72hjI2XNX). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12334.