Acute and chronic ischaemia of the lower limb

Limb ischaemia is an important clinical problem due to the high prevalence of peripheral arterial disease (PAD) in the UK. The main risk factors are smoking and diabetes mellitus. In young patients, alternative diagnoses of embolus, thrombosis, arteritis, congenital anomaly, fibrosis and traumatic (including iatrogenic) arterial injury must be considered. Intermittent claudication, critical ischaemia and acute ischaemia are clinical diagnoses easily confirmed by ankle–brachial pressure index (ABPI) measurement. Non-invasive arterial assessment by duplex, magnetic resonance angiography and computed tomographic angiography are used to confirm the diagnosis and to plan intervention. Angiography is usually reserved for therapeutic intervention. Best medical therapy for PAD includes smoking cessation, aspirin, blood pressure control (angiotensin-converting enzyme inhibitors) and statin therapy. These interventions are proven to reduce heart attack and stroke. For claudicants, structured exercise classes improve maximum and pain-free walking distance; in addition, percutaneous angioplasty may be considered if they have a suitable lesion in the iliac, femoral or popliteal arteries. Patients with critical limb ischaemia require intervention to avoid limb loss; arterial reconstruction (angioplasty or bypass) is preferable to primary amputation, as preservation of mobility is an important determinant of quality of life. The acutely ‘threatened’ limb is a surgical emergency and requires immediate intervention, best performed in a specialized vascular unit.     

Major limb amputation and mortality in patients with neuro‐ischaemic lower extremity wounds managed in a tertiary hospital: Focus on the differences among patients with diabetes,peripheral arterial disease and both

A majority of lower extremities neuro‐ischaemic wounds (NIU) are related to: (a) only diabetes (DM); (b) only peripheral artery disease (PAD); (c) co‐existing diabetes and peripheral artery disease (DM‐PAD). This study aims to characterise the major clinical outcomes of forementioned three groups of lower extremity wound patients in Singapore. Patients hospitalised for lower extremity NIU between January 2014 and October 2017 in a tertiary hospital in Singapore were analysed. Patients'' major limb amputation and mortality were assessed using Cox regression models. Cumulative survival and amputation‐free survival among the three classified groups were calculated using Kaplan‐Meier analysis. Compared with patients with only DM, those in the PAD group and the DM‐PAD group had higher risk of major limb amputation (adjusted hazard ratio: 2.47, 95% CI: 1.65‐3.70; adjusted hazard ratio: 2.01, 95% CI: 1.53‐2.65 respectively) and mortality (adjusted hazard ratio: 2.36, 95% CI: 1.57‐3.55; adjusted hazard ratio: 2.46, 95% CI: 1.86‐3.26 respectively). The 3‐year survival and amputation‐free survival were lowest in the DM‐PAD group (52.1% and 41.5% respectively), followed by the PAD group (53.3% and 44.6% respectively) and the DM group (74.2% and 68.5% respectively). Lower extremity NIU patients with PAD or DM‐PAD were found to have poorer clinical prognosis than those with DM only.     

Lowering homocysteine decreases levels and expression of VEGF(165) and endostatin

BACKGROUND: Homocysteine, vascular endothelial growth factor (VEGF), and endostatin have been implicated in angiogenesis and in the development and progression of atherothrombotic vascular disease. We sought to determine whether homocysteine modulates plasma levels of VEGF and endostatin and their expression in leukocytes in patients with peripheral arterial disease (PAD) or diabetes mellitus (DM). MATERIALS AND METHODS: Ten patients with PAD and 15 patients with type 2 DM were evaluated before and 6 wk after oral administration of folic acid and B vitamins. Evaluation included measurements of plasma levels of homocysteine, VEGF, and endostatin by enzyme-linked immunosorbent assay and the expression of VEGF and endostatin mRNAs in leukocytes using RT-PCR. The measurements were compared with baseline findings in 12 healthy subjects. RESULTS: Basal homocysteine (P < 0.001) and VEGF (P < 0.01) levels were elevated in all patients versus healthy subjects. Basal endostatin levels were lower in patients with PAD but were higher in patients with DM compared with healthy subjects (P < 0.001). In patients with PAD or DM, folic acid and B vitamins administration resulted in significant reduction (P < 0.001) of plasma levels of homocysteine (20.9% and 26.2%), VEGF (29.7% and 40.4%) and endostatin (9.4% and 5.7%), respectively. Moreover, VEGF and endostatin mRNA expression in leukocytes was down-regulated in all patients after B vitamins and folate treatment. CONCLUSION: These findings demonstrate that lowering of homocysteine with B vitamins and folic acid resulted in substantial reduction of plasma levels of VEGF but minimal reduction of endostatin and in down-regulation of their expression in leukocytes in patients with PAD or DM.     

Diabetes Mellitus,Hyperhomocystinemia and Atherosclerotic Vascular Disease in Taiwanese Chronic Hemodialysis Patients: A Retrospective Study

Aim: Diabetic patients with hemodialysis (HD) have a high mortality rate from atherosclerotic vascular disease (ASVD). However, the extent of the role of hyperhomocystinemia as a risk factor of ASVD is uncertain in diabetic HD patients. We investigated whether there was an association with ASVD events in diabetics and non‐diabetics where these were chronic hyperhomocystinemia HD patients. Methods: Two hundred patients undergoing HD were included in the study. About 50% of the patients had diabetes mellitus (DM). They had predialysis blood work performed for total homocysteine. A history of DM was elicited using information from the patients' questionnaires and verified by careful inpatient and outpatient chart review. Results: A total of 196 patients had hyperhomocystinemia and were enrolled this study. Mean homocysteine concentration was 29.7 ± 6.6 µmol/L overall. DM was present in 50.0% of patients. The mean homocysteine concentration was 29.4 ± 9.5 µmol/L and 29.9 ± 9.7 µmol/L in diabetic HD patients (n = 98) and non‐diabetic HD patients (n = 98), respectively (P = 0.71). There was no association with hyperhomocystinemia between diabetic and non‐diabetic in chronic HD patients. There were significant differences including age, sex, HDL cholesterol, triglycerides, hypertension, smoking, serum creatinine, dialysis duration and glucose intolerance in the two groups (P < 0.05). There were also significant differences in ASVD (P = 0.0027) and CVD (P = 0.0017) between diabetics and non‐diabetics in cases of chronic hyperhomocystinemia HD patients. The adjusted odds ratio for ASVD was 3.02 (95%CI, 1.63 to 5.59) for those subjects with a DM in the highest quartile compared with the lowest 3 quartiles. Conclusions: There were associations with ASVD and CVD in diabetics and non‐diabetics in cases of chronic hyperhomocystinemia HD patients. There was no association with hyperhomocystinemia between diabetic and non‐diabetic in Taiwanese chronic HD patients. This study found that the presence of DM and advanced age were the major determinants for ASVD events in chronic HD patients, rather than the levels of homocysteine.     

Quantifying comorbidity in peritoneal dialysis patients and its relationship to other predictors of survival.

BACKGROUND: Comorbidity is the single most important determinant of outcome in patients on renal replacement therapy. The aims of this study were to evaluate a semi-quantitative approach to comorbidity scoring in predicting survival of patients commencing peritoneal dialysis (PD), and to establish the interaction between this and other known predictors of patient outcome, in particular membrane function, residual renal function (RRF) and plasma albumin. METHODS: Comorbidity was recorded in a prospective, single centre cohort study of 303 patients commencing on PD. Using seven disease domains, chosen to reflect the dominance of cardiovascular morbidity in the end-stage renal failure population, comorbidity was graded as '0' when absent, '1' when one or two, and '2' when three or more conditions were present. The Wright comorbidity index, which includes age within the scoring method, was also evaluated. RRF, plasma albumin and peritoneal solute transport were measured every 6 months. Patients were censored at death. RESULTS: Median survival according to grade of comorbidity was 105, 42 and 29 months, respectively (P<0.0001), with good separation of the actuarial survival curves. Using Cox regression, the addition of age and the grade of comorbidity to Kt/V(urea), solute transport and plasma albumin increased the predictive power of the model. All were independent predictors of outcome with the exception of albumin. The Wright comorbidity index also enhanced the Cox model, although was not as powerful as when age and comorbidity were considered independently. At baseline, RRF was not different according to comorbidity unless diabetes was considered separately. Diabetics started with higher RRF, but after 6 months on PD this was the same as non-diabetic patients. Otherwise, initial rate of decline of RRF was similar across the comorbid grades, although the impact of higher drop-out due to earlier loss in patients with more comorbidity may have disguised earlier loss in these patients. Peritoneal solute transport tended to be higher in patients with increased comorbidity at baseline, chi(2) 13.8, P=0.032, and this was sustained with time on treatment. CONCLUSION: Comorbidity has a quantitative effect on survival that is independent of age, RRF and membrane function in PD patients. Comorbidity also appears to be associated with increased solute transport at the start of treatment, which is sustained. With the exception of diabetes, grade of comorbidity does not have a profound effect on loss of RRF.     

Prognostic Significance of Vascular Endothelial Growth Factor,Basic Fibroblast Growth Factor,and Angiogenin in Patients With Resectable Hepatocellular Carcinoma After Surgery

Background: Hepatocellular carcinoma (HCC) is a hypervascular malignancy. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG) are important angiogenic factors of neoangiogenesis. This study investigated the predictive value of serum VEGF, bFGF, and ANG in tumor recurrence, disease-free survival (DFS), and overall survival (OS) in HCC patients.Methods: Preoperative serum VEGF, bFGF, and ANG were measured in 98 patients with resectable HCC and in 15 healthy controls. The median follow-up time was 43 months.Results: Preoperative serum VEGF was increased in patients with resectable HCC compared with healthy controls (P < .05). Increased serum VEGF was correlated with tumor recurrence (P = .001). Univariate analysis showed that serum VEGF, tumor-node-metastasis stage, tumor size and number, macroscopic portal vein invasion, and microscopic vascular invasion were correlated with OS and DFS. Serum bFGF and ANG were not associated with survival. Multivariate analysis showed that serum VEGF was the most significant predictor of DFS (relative risk, 2.35; 95% confidence interval, 1.26–4.39; P = .007) and OS (relative risk, 3.44; 95% confidence interval, 1.81–6.57; P < .001) in HCC patients after surgical resection.Conclusions:Preoperative serum VEGF is a significant independent predictor of tumor recurrence, DFS, and OS in patients with resectable HCC.     

Level Selection in Leg Amputation for Arterial Occlusive Disease: A Comparison of Clinical Evaluation and Skin Perfusion Pressure

In 102 leg amputations for arterial occlusion including 84 below-knee (BK), 16 above-knee (AK) and 2 through-knee (TK) amputations, the amputation level was determined by means of clinical criteria. The healing results and the selection of levels were then compared with sealed preoperative measurements of the skin perfusion pressure (SPP). Out of 62 BK amputations with an SPP above 30 mmHg wound healing failed in only 2 cases (3 per cent). Out of 13 BK amputations with an SPP between 20 and 30 mmHg 7 cases (54 per cent) failed and out of 9 BK amputations with an SPP below 20 mmHg no less than 8 cases (89 per cent) failed to heal. The difference in failure rate is significant (P < 0.0001). Out of the 15 failed BK amputations at low pressures (below 30 mmHg) only one case had local signs of ischaemia, which might have warned the surgeons. On the other hand, in 13 out of the 18 cases of primary AK (or TK) amputations there were clinical signs of ischaemia of the calf, comprising temperature demarcation, cyanosis and/or necrotic skin lesion. The SPP below the knee appeared in all these cases to lie below 30 mmHg. In the 5 other cases of primary AK (or TK) amputation the knee was sacrificed for reasons other than signs of local ischaemia, e.g. poor physical or mental condition. It was moreover found that the presence of pulsations in the popliteal artery indicated an 89 per cent chance of healing of BK amputations. Infection was present in 24 BK amputations (28 per cent) and equally frequent among diabetic and non-diabetic cases. The postoperative SPP measured on the stumps averaged only 5 mmHg (P <0.05) higher than the preoperative SPP explaining why the preoperative SPP related closely to the postoperative course. It is concluded that ischaemia at the BK election site cannot be ruled out by clinical assessment alone and that preoperative determination of the SPP can be used in determining the chance of healing in BK amputations.