Diabetes and peripheral arterial disease

Background: Diabetes mellitus increases the risk for peripheral arterial disease (PAD) early in life and the disease is likely to progress to advanced stages. Mechanisms responsible for premature PAD in diabetes are partly unknown. Leg ischaemia from PAD, together with other diabetic complications, is the key player in the pathway from ulceration to gangrene and infection, which ultimately results in major amputation. Infrainguinal bypass surgery (IBS) is carried out to restore leg perfusion and avoid amputations. Whether outcomes for this procedure are less favourable in patients with diabetes than in patients without diabetes is unclear. Aims: ‒To explore the impact of hyperglycaemia on outcome after IBS in patients with diabetes. ‒To assess amputation-free survival (AFS) after IBS for critical limb ischaemia. ‒To assess amputation-free survival (AFS) in patients with diabetes but without PAD during long term follow up. ‒To investigate if receptor for advanced glycation end products (RAGE) and advanced glycation end products (AGE) are increased in plasma and vein grafts in diabetes patients. ‒To investigate if the AGE-RAGE system predicts AFS and development of PAD, and if it is associated with AFS after IBS in patients with diabetes. Results: In Paper I, we demonstrated an association between hyperglycaemia the first 48 hours after IBS and increased risk for wound complications, graft occlusion and amputation or death during the first 3 months in 91 patients with diabetes. Patients in the highest quartile of glucose exposure had an odds ratio of 13‒14 in multivariate logistic regression. In Paper II, we performed a nationwide, population-based cohort study and compared postoperative AFS in patients with and without diabetes. The analysis included data for 1 840 patients from the Swedish Vascular Registry who, during 2001–2003, underwent their first unilateral, below-knee, IBS procedure for critical limb ischaemia. Of these patients, 742 had diabetes and 1,098 did not. Patients were followed up until the end of 2005. Overall, 446 and 558 patients with and without diabetes, respectively, had undergone ipsilateral amputation or died by the end of the follow-up period. Patients with diabetes had a shorter AFS than patients without diabetes (2.3 years, 95% CI 1.9–2.8 years versus 3.4 years, 95% CI 3.1–3.7 years). The hazard ratio and incidence for ipsilateral amputation or death in patients with diabetes, adjusted for age, sex, smoking and other confounding variables, was 1.46 (95% CI 1.26–1.69) and 30.2 events per 100 person-years respectively. The incidence of amputation or death was 2.8 per 100 person-years, (95% CI 2.0 to 3.7) in the cohort of patients with type 2 diabetes who were free from PAD at start of follow up. In Paper III and IV we showed that S100A12, a ligand to RAGE, is associated with AFS after IBS in patients with (n=38) and without (n=30) diabetes, and with AFS as well as development of PAD in a prospective longitudinal (10-year) population-based cohort (n=146) of patients with type 2 diabetes, free from signs of PAD at inclusion. Presence of AGE, RAGE and S100A12 were demonstrated in saphenous vein tissue with no difference between patients with and without diabetes. Conclusions: Postoperative hyperglycaemia is associated with unfavourable outcome after IBS in patients with diabetes. Diabetes is associated with lower AFS after IBS for critical limb ischaemia. Plasma levels of S100A12 and RAGE components are elevated in PAD disease and markers of RAGE and its ligands are found in vein tissue used for bypass. This is consistent with a role for S100A12 in PAD complications by activation of the RAGE system. Higher plasma levels of S100A12 and the combined effect of RAGE components seem to be associated with AFS in patients with diabetes. Further study is needed to find methods of reducing this excess risk and prolonging AFS

Additional file 1: of 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

Table S1.Baseline characteristics for all patients in the original cohort. Data are means and SD (standard deviation) or n (%). a PAD defined as amputations or loss of foot pulse. b Albuminuria >300 mg/L or S-creatinine above 100 mmol/L in women and 110 mm/L in men. c Two patients had undergone both major and minor amputations. d P = .073 (Fisher’s Exact Test), e P = .072 (Fisher’s Exact Test), f P = .059 (Mann-Whitney U)

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

Abstract 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