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Aim Diabetic foot ulcer (DFU) is a major complication of both Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D); however research into risk factors for DFU does not separate between these two types. The purpose of the present investigation was to identify risk factors for development of first time DFU (FTDFU) over a period of 15 years in patients with T1D and T2D separately. Methods This retrospective cohort study included 25,220 feet from 5588 patients with T1D and 7113 patients with T2D treated in the period 2001–2015. Data on baseline characteristics and comorbidities were collected from electronic patient records. Influences of various risk factors for the development of FTDFU were assessed by hazard ratios (HR) from Cox proportional hazard regression models on time from enrolment to FTDFU diagnosis or end-of-follow-up. Results In T1D independent risk factors were male sex, age >60 years, high HbA1c, long diabetes duration, history of cardiovascular disease, macro-albuminuria, decreased visual acuity, advanced diabetic retinopathy, decreased/absent vibration sense, presence of patient reported symptoms of neuropathy, and absence of foot pulses. In T2D the independent risk factors were the same except age >60 years, a history of cardiovascular disease, and long diabetes duration. Conclusions This study documents that much of the standard clinical information obtained as part of the routine follow-up are also independent risk factors for development of FTDFU. This may be used to create a basis for in which patient and when prevention should be started.

Aims Charcot foot is a rare but disabling complication to diabetic neuropathy, and can cause permanent, limb-threatening deformities. The aim of this study was to investigate a population of patients a Charcot foot on a case-by-case basis, in order to assess the consequences of an acute Charcot foot and its complications. Methods The study was conducted a retrospective study of patients admitted to the Copenhagen Wound Healing Center between 1996 and 2015 with the diagnosis of Charcot foot (DM14.6) and diabetes mellitus type 1 or 2 (DE10.X and DE11.X). Physical and electronic records were used, and compared to data from the Danish Diabetes Registry. Results In total 392 patients were identified of which 173 were included. There were 26% with type 1 diabetes (initial HbA1c 81.7 ± 21.4 mmol/mol) and 74% with type 2 diabetes (initial HbA1c 66.5 ± 20.3 mmol/mol). Primary off-loading was with a removable walker in 95% of the cases (average off-loading time 8.3 months). The 5-year mortality was 14% with a mean survival time of 12.7 years. There was an association between lack of compliance and occurrence of foot complications, as well as between having a Charcot foot and leaving the workforce. Conclusion More patients had type 1 diabetes compared to the background population, and they had a higher HbA1c than the general population of diabetes patients. A total of 67% developed complications such as ulcers, while patients non-compliant to treatment did significantly worse than those being compliant. The 5-year mortality was low, 14%, and comparable to diabetes patients without Charcot foot.

Objective Charcot foot is a severe complication to diabetes mellitus, associated with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress of neuropathy are still largely unexplored. The objective was to investigate whether a previous Charcot foot had any long-term effects on the progress of neuropathy. Results An 8.5-year follow-up case–control study of 49 individuals with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in 2005–2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart rate variability and venous occlusion plethysmography. Of the 49 baseline participants, 22 were able to participate in the follow-up. Twelve had passed away in the meantime. Heart rate variability was unchanged in both groups; from 9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p = 0.946), but a significantly worsened sensitivity in the control group (from 25.1 to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic or cardial autonomic neuropathy present at baseline had disappeared at follow-up after 8.5 years.

Background Treatment of Charcot osteoarthropathy (COA) requires restricted walking and offloading for several months, which lead to fat re-distribution and increased sarcopenia. Objectives/Aim To investigate whether subjects with COA have an altered body composition compared to controls. Methods Cross-sectional case-control study of people with diabetes with acute or chronic Charcot osteoarthropathy, matched with otherwise healthy people with diabetes. A total of 49 subjects (distribution ~ 1:1) had a total body DXA-scanning, measuring appendicular lean mass, android/gynoid and truncal/total body fat distribution ratios. Results Sarcopenia frequency was higher in the total population with diabetes overall (9–40%), compared to normal materials. Using two different models for correlating appendicular lean mass to sarcopenia, there were no differences in sarcopenia-rates between the groups (P = 0.413 and 0.948 respectively). There was no significant difference in lean tissue mass between the affected and the unaffected leg in the immobilised subject group (P = 0.830). The average fat percentage was (29.4–37.7%) in the population with diabetes, compared to a matching background population (24.5–31.9%), whereas there were no significant differences found between the groups (P = 0.065). Neither truncal/total fat percent nor android/gynoid fat percent ratios showed differences between the groups. Conclusion To our knowledge, this is the first published dataset investigating body composition in subjects with Charcot osteoarthropathy. The study population of diabetics were more fat and sarcopenic than normal subjects, whereas no statistically significant impact of Charcot osteoarthropathy was found.

OBJECTIVE Infection commonly complicates diabetic foot ulcers and is associated with a poor outcome. In a cohort of individuals with an infected diabetic foot ulcer, we aimed to determine independent predictors of lower-extremity amputation and the predictive value for amputation of the International Working Group on the Diabetic Foot (IWGDF) classification system and to develop a risk score for predicting amputation. RESEARCH DESIGN AND METHODS We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries. RESULTS Among these patients, 159 (28%) underwent an amputation. Independent risk factors for amputation were as follows: periwound edema, foul smell, (non)purulent exudate, deep ulcer, positive probe-to-bone test, pretibial edema, fever, and elevated C-reactive protein. Increasing IWGDF severity of infection also independently predicted amputation. We developed a risk score for any amputation and for amputations excluding the lesser toes (including the variables sex, pain on palpation, periwound edema, ulcer size, ulcer depth, and peripheral arterial disease) that predicted amputation better than the IWGDF system (area under the ROC curves 0.80, 0.78, and 0.67, respectively). CONCLUSIONS For individuals with an infected diabetic foot ulcer, we identified independent predictors of amputation, validated the prognostic value of the IWGDF classification system, and developed a new risk score for amputation that can be readily used in daily clinical practice. Our risk score may have better prognostic accuracy than the IWGDF system, the only currently available system, but our findings need to be validated in other cohorts.

BACKGROUND AND AIMS: Charcot foot is a rare but severe complication to diabetes and peripheral neuropathy. It is still unclear if an acute Charcot foot has long-term effects on the bone metabolism. To investigate this, we conducted a follow-up study to examine if a previously acute Charcot foot has any long-term effects on bone mineral density (BMD) or local or systemic bone metabolism.METHODS: An 8.5-year follow-up case-control study of 44 individuals with diabetes mellitus, 24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005-2007, who were followed up in 2015 with DXA scans and blood samples.RESULTS: 21 of the 44 baseline participants participated in the follow-up. There were no difference in the change in total hip BMD from baseline to follow-up in either the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of osteoporosis in the previous Charcot feet either. From baseline to follow-up, there was a significant difference in the change in levels of fsRANK-L in the Charcot group, but not in the control group (p = 0.002 and 0.232, respectively). At follow-up, there were no differences in fsRANK-L between the groups. The fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3 versus 1.1) (p = 0.302).CONCLUSION: We found that diabetes patients with an acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level decreased from baseline to follow-up to be comparable to the level in diabetes patients without previous or current Charcot foot. We found no permanent effect of an acute Charcot foot on hip or foot BMD.

Background Healing of heel ulcers in patients with diabetes is considered to be poor, but there is relatively little information on the influence of ulcer location on ulcer healing. Methods The influence of ulcer location on time to healing of diabetic foot ulcers was analysed by multivariate Cox regression analysis for 1000 patients included in the Eurodiale study, a prospective cohort study of patients with diabetic foot disease. Results Median time to healing was 147 days for toe ulcers [(95% confidence interval (CI) 135–159 days)], 188 days for midfoot ulcers (95% CI 158–218 days) and 237 days for heel ulcers (95% CI 205–269 days) (p

Aims: Diabetic complications, and in particular diabetic foot ulcers (DFUs), are associated with low health-related quality of life (HRQoL). We evaluated whether the presence of diabetic complications also influenced the improvement of HRQoL during DFU treatment.Methods: 1088 patients presenting for DFU treatment at the centers participating in the Eurodiale study were followed prospectively up to one year. HRQoL was measured both at presentation and after healing or at end of follow up, using EQ-5D: a standardized instrument consisting of five domains and a summary index. The influence of diabetic comorbidity on the course of HRQoL was evaluated for each of the EQ-5D outcomes in multi-level linear regression analyses, adjusting for baseline characteristics.Results: HRQoL improved in all EQ-5D outcomes over the course of treatment for those DFUs that healed. The few significant differences in the development of HRQoL between patients with and without comorbidity showed a more beneficial development for patients with comorbidity in DFUs that did not heal or healed slowly.Conclusions: Comorbidity does not hamper improvement of HRQoL in DFU treatment. On the contrary, HRQoL improved sometimes more in patients with certain comorbidity with hard-to-heal ulcers. (C) 2017 Elsevier Inc. All rights reserved.

Objective Recent literature on acute diabetic Charcot osteoarthropathy (CA) reports unusually long periods of off-loading. Data suggest that this might increase the re-currence rate. Subsequently we evaluated the influence of duration of off-loading on the risk of required re-casting. Research Design and Methods In this retrospective consecutive series from 2000 to 2005, 56 people with diabetes and an acute Charcot foot were included. The inclusion criteria were an initial persistent temperature difference more than 2°C between the two feet, oedema, and typical hot spots on a bone scintigram, radiology, and a typical clinical course. Treatment was off-loading in a removable cast and 2 crutches. In-door walking was allowed. Gradually augmented weight bearing was prescribed when the skin temperature difference had decreased to a level less than 2°C and edema had subsided. Re-casting was required for immediate exacerbation during re-load as well as for recurrence — defined as new swelling and skin temperature difference of more than 2°C in the same foot occurring after a stable interval of at least one month after full weight bearing. Results The duration of off-loading for all patients was 141±21days (mean±SD). Three patients (5%) were re-casted immediately for exacerbation after re-load and 7 patients (12 %) after recurrence of the CA. Duration of re-casting was 79±44days. The primary period of off-loading was not statistically significantly different for those not requiring versus those requiring re-casting: 142±24days compared to 134±41days. Neither were the differences in demographic data, metabolic regulation, BMI or localization of CA. Conclusions Patients with risk of exacerbation or recurrence of CA could not be identified in the present study and there was no relation to the duration of off-loading. Nevertheless off-loading periods with immobilisation should be kept as short as possible, due to other side effects. This can be obtained by early gradual augmented re-loading.

Objectives The incidence of minor amputation may vary significantly, and determinants of minor amputation have not been studied systematically. We evaluated minor amputation rate, the determinants of minor amputation and differences in amputation rate between European centres. Methods In the Eurodiale study, a prospective cohort study of 1232 patients (1088 followed until end-point) with a new diabetic foot ulcer were followed on a monthly basis until healing, death, major amputation or up to a maximum of 1 year. Ulcers were treated according to international guidelines. Baseline characteristics independently associated with minor amputation were examined using multiple logistic regression modelling. Based on the results of the multivariable analysis, a disease severity score was calculated for each patient. Results One hundred and ninety-four (18%) patients underwent a minor amputation. Predictors of minor amputation were depth of the ulcer (odds ratio 6.08, confidence interval 4.10-9.03), peripheral arterial disease (odds ratio 1.84, confidence interval 1.30-2.60), infection (odds ratio 1.56, confidence interval 1.05-2.30) and male sex (odds ratio 1.42, confidence interval 0.99-2.04). Minor amputation rate varied between 2.4 and 34% in the centres. Minor amputation rate in centres correlated strongly with disease severity score at the moment of presentation to the foot clinic (r = 0.75). Conclusions Minor amputation is performed frequently in diabetic foot centres throughout Europe and is determined by depth of the ulcer, peripheral arterial disease, infection and male sex. There are important differences in amputation rate between the European centres, which can be explained in part by severity of disease at presentation. This may suggest that early referral to foot clinics can prevent minor amputations.

Aims/hypothesis Outcome data on individuals with diabetic foot ulcers are scarce, especially in those with peripheral arterial disease (PAD). We therefore examined the clinical characteristics that best predict poor outcome in a large population of diabetic foot ulcer patients and examined whether such predictors differ between patients with and without PAD. Methods Analyses were conducted within the EURODIALE Study, a prospective cohort study of 1,088 diabetic foot ulcer patients across 14 centres in Europe. Multiple logistic regression modelling was used to identify independent predictors of outcome (i.e. non-healing of the foot ulcer). Results After 1 year of follow-up, 23% of the patients had not healed. Independent baseline predictors of non-healing in the whole study population were older age, male sex, heart failure, the inability to stand or walk without help, end-stage renal disease, larger ulcer size, peripheral neuropathy and PAD. When analyses were performed according to PAD status, infection emerged as a specific predictor of non-healing in PAD patients only. Conclusions/interpretation Predictors of healing differ between patients with and without PAD, suggesting that diabetic foot ulcers with or without concomitant PAD should be defined as two separate disease states. The observed negative impact of infection on healing that was confined to patients with PAD needs further investigation.

Background and aim The bone-related peptide osteoprotegerin has been linked to vascular calcification and peripheral vascular disease. We investigated the association between osteoprotegerin and development of foot complications in persons with type 1 diabetes. Materials and methods Prospective observational study of 573 persons with type 1 diabetes, 225 women; age [mean±SD] 42.3±10.3years. Plasma osteoprotegerin was measured by ELISA. Results Median (IQR) osteoprotegerin was 2.80(2.35–3.63)μg/L and follow-up time (median (range)) was 12.7(0.1–15.6)years. Endpoints included: new foot ulceration ( n =153), Charcot foot ( n =14), vascular surgery/amputation ( n =53), loss of foot pulse ( n =57), and peripheral neuropathy ( n =99). In unadjusted analyses, higher osteoprotegerin was associated with development of all endpoints ( p ≤0.026). Higher osteoprotegerin remained associated with development of foot ulcer, and the combination of vascular surgery/amputation, loss of foot pulse and neuropathy ( p ≤0.001) in a sex and age adjusted model. After further adjustment (nephropathy status, smoking, HbA 1c , systolic blood pressure, serum cholesterol, high sensitivity C-reactive protein, eGFR, and presence of neuropathy and/or claudication and/or foot ulcer at baseline), higher osteoprotegerin remained associated with development of foot ulcer (HR (95% CI) per doubling: 1.75 (1.04–2.97); p =0.037). Conclusion Higher osteoprotegerin levels were associated with development of foot ulcer, even after comprehensive adjustment.

The unstable or misaligned Charcot ankle with or without chronic foot ulceration is a major clinical challenge. When it cannot be accommodated with an ankle foot orthosis, surgical treatment is indicated in order to avoid leg amputation. This requires extensive soft tissue release and bony resection to realign the foot and arthrodesis with internal or external fixation. The guidance in the literature favors internal fixation. This article reports results with external fixation in 11 patients (12 feet) over a period of 12 years. External fixation was chosen as the surgical option because of the presence of foot ulcers with the attendent risk of infection. There were 7 tibio-talar and 5 tibio-calcaneal fusions. Compression was applied for 6 weeks with an external frame according to Charnley, followed by 6 weeks with total-contact cast. Weight bearing with a rigid leather brace was allowed after 12 weeks. In one case, transtibial amputation was required due to loosening of the distal pins from osteopenic disintegrating bone. In 11 cases (92%), the foot was successfully realigned and independent walking with a brace retained during the follow-up of median 48 months (10-102 months). Bony union took place in 5 out of 7 cases with tibio-talar fusion and in 1 out of 5 with tibio-calcaneal fusion. The functional result in cases with fibrous union was, however, satisfactory. Although meaningful comparisons of series are difficult to conduct and interpret from, the limb salvage rate was similar to results with internal fixation. The authors consider the results to be encouraging and to be used to develop a higher level of evidence.

Chronic wounds and in particular diabetic foot ulcers (DFUs) are a growing clinical challenge, but the underlying molecular pathophysiological mechanisms are unclear. Recently, we reported reduced levels of the immunomodulating and antimicrobial S100A8/A9 in non-healing venous leg ulcers (VLUs), while another study found increased S100A8/A9 in DFUs. To clarify these apparently contradictory findings, we compared S100A8/A9 as well as an inducer, lipopolysaccharide (LPS) and selected innate immune response mediators in wound fluids from non-healing DFUs and VLUs with healing wounds. Wound fluids were collected from neuropathic DFUs (n = 6) and VLUs (n = 9) of median 2-year duration, and split-thickness skin graft donor site wounds (n = 10) by standardized method. None of the patients had ischaemic extremities or clinically infected wounds. LPS was determined by limulus amoebocyte lysate test, and S100A8/A9, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-10 and vascular endothelial growth factor (VEGF) by immunospecific quantitative assays. LPS levels were median 8.7 (interquartile range 5.4-21.2) ng/ml in DFUs compared with 121 (22-2000) ng/ml in VLUs. S100A8/A9 was higher (p = 0.020) in DFUs [718 (634-811) µg/ml] than in VLUs [303 (252-533) µg/ml]. Neither G-CSF nor IL-10 wound fluid levels differed significantly between the chronic wound groups. VEGF levels correlated with LPS (r = 0.758, p = 0.011, n = 10) and were higher (p = 0.024) in VLU wound fluids. LPS (p

Background Recent reports on Achilles tendon lengthening (ATL) have documented rapid healing of chronic plantar neuropathic forefoot ulcers. Methods Sixty-eight patients with 75 ulcerated neuropathic feet (63 patients with diabetes with 69 ulcerated feet) underwent ATL and were retrospectively studied for chronic plantar ulceration in the forefoot and reduced dorsiflexion range of motion at the ankle. Median duration of ulcers was 48 months (range 11-84 months) in 16 forefoot amputation stumps and 11 months (range 3-84 months) for the rest of the patients. Results Healing of the ulcers was obtained in 68/75 feet (91%). At a median follow-up of 12 months (3-26 months), 4 had never healed, 5/10 recurrent ulcers and 6/11 transfer ulcers (localized to the heel) had not healed, that is, a healing rate of 60/75 (80%). Acute transfer ulcers to the heel occurred in 47% of patients with complete anaesthesia of the heel pad. Late heel ulceration occurred in 14% of those with extreme ankle dorsiflexion (>15 degrees). Failure to heal or ulcer recurrence occurred more frequently at dorsiflexion

Aims/hypothesis. To assess the results of the strategy used in avoiding major amputations in patients with diabetes mellitus. Methods. A retrospective study for the years 1981 to 1995 in a central district hospital in Copenhagen with a catchment area population of about 178000. Results. There were 463 major leg amputations and the incidence decreased from 27.2 to 6.9/100000 population (minus 75%). The decrease in patients with Type I diabetes mellitus was from 10.0 to 4.1 (minus 59%) and in Type II diabetes mellitus from 17.2 to 2.8/100000 people (minus 84% ). Analysis showed that the diabetic population remained constant despite a considerable fall in the number of older people. During the study period infra-popliteal arterial bypass was introduced for the treatment of critical lower limb ischaemia and in diabetic patients the number of bypasses increased from 0 to 13/100000 population. The total number of revascularisation procedures in people with diabetes increased from 2.6 to 19.2/100000 population. Moreover, a multidisciplinary diabetic foot clinic was established. Conclusion/interpretation. A 75% reduction in the incidence of major amputations coincided with a sevenfold increase in revascularization procedures and the establishment of a multidisciplinary diabetic foot clinic suggesting these measures are important in the prevention of diabetic leg amputations.

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0.5-1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the 133Xewashout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8.0 +/- 1.0 mmol l-1 vs. 8.5 +/- 1.1 mmol l-1) (P < 0.02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3.2 +/- 0.2 mmol l-1 vs. 2.1 +/- 0.3 mmol l-1) (P < 0.01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.

AimTo identify the factors responsible for the low health-related quality of life associated with foot ulcers and the relative importance of these factors. MethodsA total of 1232 patients with a new foot ulcer, who presented at one of the 14 centres in 10 European countries participating in the Eurodiale study, were included in this cross-sectional study. Patient and ulcer characteristics were obtained as well as results from the Euro-Qol-5D questionnaire, a health-related quality of life instrument with five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). To analyse the relative importance of comorbidities and ulcer- and patient-related factors for health-related quality of life, linear regression models were used to calculate the relative contributions of each factor to the fit (R-2) of the model. ResultsPatients reported poor overall health-related quality of life, with problems primarily in the mobility and pain/discomfort domains. Among the comorbidities, the inability to stand or walk without help was the most important determinant of decreased health-related quality of life in all five domains. Among ulcer-related factors, ulcer size, limb-threatening ischaemia and elevated C-reactive protein concentration also had high importance in all domains. The clinical diagnosis of infection, peripheral arterial disease and polyneuropathy were only important in the pain/discomfort domain. ConclusionsThe factors that determine health-related quality of life are diverse and to an extent not disease-specific. To improve health-related quality of life, treatment should not only be focused on ulcer healing but a multifactorial approach by a specialized multidisciplinary team is also important. What's new? The inability to stand or walk without help is the most important determinant of poor health-related quality of life. Other factors with high importance are ulcer size, elevated C-reactive protein concentration and limb-threatening ischaemia. To improve health-related quality of life, treatment should not only be focused on ulcer healing but a multifactorial approach by a specialized multidisciplinary team is also important.

Background: Health-related quality of life (HRQoL) is poor in patients with persistent diabetic foot ulcers and poor HRQoL predicts worse outcomes in these patients. Amputation is often considered a treatment failure, which is why conservative treatment is generally preferred over amputation. However, it is unclear whether minor amputation negatively affects HRQoL compared with conservative treatment in patients with diabetic foot ulcers. Methods: In the cohort of the multicenter, prospective, observational Eurodiale study, we determined difference in change of HRQoL measured by EQ-5D between patients with a diabetic foot ulcers that healed after conservative treatment (n = 676) and after minor amputation (n = 145). Propensity score was used to adjust for known confounders, attempting to overcome lack of randomization. Results: Baseline HRQoL was not significantly different between patients treated conservatively and undergoing minor amputation. In addition, there was no difference in the change of HRQoL between these groups. In patients who healed 6 to 12 months after the first visit, HRQoL on the anxiety/depression subscale even appeared to improve more in those who underwent minor amputation. Conclusions: Minor amputation was not associated with a negative impact on HRQoL in patients with a diabetic foot ulcers. It may therefore not be considered treatment failure in terms of HRQoL but rather a viable treatment option. A randomized controlled trial is warranted to further examine the influence of minor amputations on health-related quality of life. (Less)

Aim The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA). Methods Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest was the patients with acute Charcot foot ( n =17) or chronic Charcot foot ( n =7). The inclusion criterion for an acute Charcot foot was a temperature difference of more than 2° between the two feet, oedema of the affected foot, typical hotspots in a bone scintigram and a typical clinical course. In addition, patients with first toe amputation ( n =5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with ( n =9) or without somatic neuropathy ( n =11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic neuropathy was done by the Neuropathy Disability Score and modified Neuropathy Symptom Score. Quantitation of autonomic neuropathy was done by measurements of local venoarteriolar sympathetic axon reflex in the feet and of heart rate variability during deep breathing and orthostatic challenge. Results The patients with acute Charcot foot and first toe amputation had an increased blood flow in the affected foot and weakened but not absent venoarteriolar sympathetic axon reflex. In the other patient groups, a normal venoarteriolar sympathetic axon reflex in the feet was found. Conclusions Peripheral sympathetic neuropathy is not likely to be the pathophysiologic mechanism behind the hyperemia in the foot during an acute attack of CA. The hyperemia is more likely secondary to local inflammatory events.

Summary Objective: To measure bone mineral density in patients with diabetes mellitus and the complication Charcot osteoarthropathy (CA). Research design and methods: A total of 49 patients with diabetes were investigated. The population consisted of patients with an acute CA (n = 17) or chronic CA (n = 7). Control groups consisted of diabetes patients with (n = 9) and without neuropathy (n = 11) and who had an amputation of the first toe (n = 5). Values measured were bone mineral density (BMD) in lumbar spine, hip and calcaneus, using lunar DEXA scanner. The bone turnover markers CTX-1 and N-MID were measured. Results: There were no differences in BMD measured in the spine and hip. There was an increase in the markers of bone turnover in the patients with acute CA. The BMD of the calcaneus was statistically lower in the affected foot in patients with chronic Charcot (P

The aim of this study was to describe the epidemiology of chronic wounds in a large cohort of patients from a tertiary hospital out-patient clinic, and examine the significance of serum mannan-binding lectin for the occurrence and clinical presentation of such wounds. The study comprised 489 consecutive patients with chronic foot and leg ulcers. A clinical classification of wound- aetiology was performed, and mannan-binding lectin was measured in the sera of patients and healthy controls. The patients presented with 639 wounds altogether; diabetic foot ulcers (309), venous leg ulcers (188), arterial ulcers (109), and vasculitis (33). The mannan-binding lectin levels of patients with venous leg ulcer, alone or in combination with other types of wounds, differed significantly from the control group, and the frequency of values100 ng/ml was significantly higher. In diabetic and arterial ulcer patients the frequency of valuesor= 3000 ng/ml was significantly higher than that of the control group. This suggests a role for the innate immunity in the pathology of venous leg ulcers, and indicates different roles for mannan-binding lectin in the development of ulcers with different aetiologies; it further suggests that mannan-binding lectin substitution should be tested in a controlled clinical trial.

In an attempt to establish the prevalence of abdominal aortic aneurysm (AAA) in outpatients with intermittent claudication (IC), 295 patients had ultrasonic screening of their abdominal aorta. There were 123 women and 172 men, median age sixty-eight years range from thirty-eight to eighty-six years. Prevalence of AAA was 5.5% (16/291 patients; examination was inconclusive in 4). All of the AAAs except 1 were found in patients older than sixty years. The prevalence in women was high and there was no significant difference between the sexes in number of AAAs: men, 12/172; women, 4/123 (p > 0.16). Of all patients, 71% were smokers and 13 AAAs were in smokers. No AAAs were found in nons mokers. 3 AAAs were found among 27 patients with unknown smoking status. The percentage of smokers was about equal in the two sexes. Because only one third of the AAAs were identified by abdominal palpation, it was insufficient as a screening procedure. The authors conclude that patients of both sexes and more than sixty years old with IC should be offered ultrasonic screening for AAA.

Removal of fibrin from the site of a newly dilated femoro-popliteal occlusion may be an attractive way of preventing rethrombosis. A double balloon catheter with a dilating tip balloon and an occlusive balloon 10, 15 or 20 cm approximately were introduced percutaneously. Following successful dilatation of femoro-popliteal occlusions, the balloons were inflated on both sides of the lesion. The dilated segment was then isolated from the circulation. Through a sideport between the balloons 5 mg of tissue type plasminogen activator and 1000 IU of heparin were installed within the segment for 30 min. The authors report the results of 53 technically successful dilatations of femoro-popliteal occlusions followed by enclosed thrombolysis. A 100% patency at 3 months was noted in 33 patients having one to three run-off arteries, and the one year patency was 90%. In 20 patients, with no infrapopliteal run-off artery, four rethrombosis occurred within 24 h, and the one year patency was 62%. This difference is significant. (Log rank test, Chi-square = 4.73, p less than 0.05). We conclude that enclosed thrombolysis prevents early reocclusion following PTA of femoro-popliteal occlusions provided that at least one infra-popliteal artery is patent.

Charcot's arthropathy is a rare complication to diabetes with peripheral neuropathy. The diagnosis is based on a red, oedematous foot with 2 degrees C difference in skin temperature between the affected foot compared to the unaffected foot. The condition is characterised by fractures, dislocation of joints and deformity. The treatment is off-loading. When the off-loading treatment is completed, the patient should gradually adjust to wearing bespoken shoes. Lifelong control of the feet and shoes is necessary.

Aims To determine current management and to identify patient-related factors and barriers that influence management strategies in diabetic foot disease. Methods The Eurodiale Study is a prospective cohort study of 1232 consecutive individuals presenting with a new diabetic foot ulcer in 14 centres across Europe. We determined the use of management strategies: referral, use of offloading, vascular imaging and revascularization. Results Twenty-seven percent of the patients had been treated for > 3 months before referral to a foot clinic. This varied considerably between countries (6-55%). At study entry, 77% of the patients had no or inadequate offloading. During follow-up, casting was used in 35% (0-68%) of the plantar fore- or midfoot ulcers. Predictors of use of casting were male gender, large ulcer size and being employed. Vascular imaging was performed in 56% (14-86%) of patients with severe limb ischaemia; revascularization was performed in 43%. Predictors of use of vascular imaging were the presence of infection and ischaemic rest pain. Conclusion Treatment of many patients is not in line with current guidelines and there are large differences between countries and centres. Our data suggest that current guidelines are too general and that healthcare organizational barriers and personal beliefs result in underuse of recommended therapies. Action should be undertaken to overcome these barriers and to guarantee the delivery of optimal care for the many individuals with diabetic foot disease.

The aim of the present study was to investigate resource utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in resource utilisation between individuals with or without peripheral arterial disease (PAD) and/or infection.Data on resource utilisation were collected prospectively in a European multicentre study. Data on 1,088 patients were available for the analysis of resource use, and data on 821 patients were included in the costing analysis. Costs were calculated for each patient by multiplying the country-specific direct and indirect unit costs by the number of resources used from inclusion into the study up to a defined endpoint. Country-specific costs were converted into purchasing power standards.Resource use and costs varied between outcome groups and between disease severity groups. The highest costs per patient were for hospitalisation, antibiotics, amputations and other surgery. All types of resource utilisation and costs increased with the severity of disease. The total cost per patient was more than four times higher for patients with infection and PAD at inclusion than for patients in the least severe group, who had neither.Important differences in resource use and costs were found between different patient groups. The costs are highest for individuals with both peripheral arterial disease and infection, and these are mainly related to substantial costs for hospitalisation. In view of the magnitude of the costs associated with in-hospital stay, reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease.

One hundred and thirty-seven consecutive percutaneous transluminal angioplasties (PTA) were performed for femoropopliteal vascular disease including 58 stenoses and 79 total occlusions. Nine occlusions could not be crossed with the guidewire, but in the remaining 128 the haemodynamic and clinical success as well as vascular patency were evaluated. The results were grouped into the following subsets: the indication for PTA, the severity of the vascular lesion, the crural run-off and the length of lesion. The results were in every respect poor with total occlusions when compared with stenoses. This was explained by a high incidence (41%) of rethrombosis within hours of dilatation. Early rethrombosis was seen with all lengths of occlusion (1–27 cm) with no statistically significant difference from other subsets. This study concludes that conventional PTA in femoropopliteal occlusions should be reserved for cases of limb salvage, preferably in patients who are technically inoperable. We suggest a new technique of segmentally enclosed thrombolysis to prevent early rethrombosis after PTA in femoropopliteal occlusions.

This article describes the rationale and protocol of a large data collection study in patients with new diabetic foot ulcers by the Eurodiale study group, a consortium of centers of expertise in the field of diabetic foot disease within Europe. This study is a multicenter, observational, prospective data collection study. Its main aim is to determine the major factors determining clinical outcome and outcome in terms of health-related quality of life and health care consumption. Between September 1, 2003, and October 1, 2004, in 14 European centers, all consecutive patients with diabetes and a new foot ulcer were included in the study and followed until the end point or for a maximum of 1 year. End points were healing of the foot, major amputation, or death. Data were collected on patient, foot, and ulcer characteristics and on diagnostic and management procedures. Furthermore, data were collected on health care organization, quality of life, and resource use. A total of 1232 patients were included in the study. Sixty-three percent of the patients were referred by their general practitioner or were self-referrals. Twenty-seven percent of the patients were admitted at the time of inclusion; 1088 patients were followed until the end point. “Optimal Organization of Health Care in Diabetic Foot Disease” is one of the first large multicenter studies in the field of diabetic foot disease on clinical presentation, clinical outcome, quality of life, resource utilization, and health care organization and their interrelationships. These data will provide us with new insights that enable us to improve care for these patients and guide the development of new studies in this area. The results of this study are the subject of a separate presentation.

Large clinical studies describing the typical clinical presentation of diabetic foot ulcers are limited and most studies were performed in single centres with the possibility of selection of specific subgroups. The aim of this study was to investigate the characteristics of diabetic patients with a foot ulcer in 14 European hospitals in ten countries. The study population included 1,229 consecutive patients presenting with a new foot ulcer between 1 September 2003 and 1 October 2004. Standardised data on patient characteristics, as well as foot and ulcer characteristics, were obtained. Foot disease was categorised into four stages according to the presence or absence of peripheral arterial disease (PAD) and infection: A: PAD -, infection -; B: PAD -, infection +; C: PAD +, infection -; D: PAD +, infection +. PAD was diagnosed in 49% of the subjects, infection in 58%. The majority of ulcers (52%) were located on the non-plantar surface of the foot. With regard to severity, 24% had stage A, 27% had stage B, 18% had stage C and 31% had stage D foot disease. Patients in the latter group had a distinct profile: they were older, had more non-plantar ulcers, greater tissue loss and more serious comorbidity. According to our results in this European cohort, the severity of diabetic foot ulcers at presentation is greater than previously reported, as one-third had both PAD and infection. Non-plantar foot ulcers were more common than plantar ulcers, especially in patients with severe disease, and serious comorbidity increased significantly with increasing severity of foot disease. Further research is needed to obtain insight into the clinical outcome of these patients.

A consecutive series of 89 patients (95 limbs) with gangrene were operated on with amputation of toes or some distal part of the foot after arterial reconstruction. 43 patients had diabetes. Healing was achieved in 81/82 feet when the reconstruction was open. Amputation below or above the knee was required in 4/5 limbs when the reconstruction failed. 8 patients died before healing. The median time to healing was 30 (17-452) days, after a single amputation, and 115 (36-466) days, when more than one procedure had been necessary. We concluded that amputations on the feet for gangrene usually heal after arterial reconstruction, in patients with diabetes as well as in those with arteriosclerosis. No weight bearing and control of infection are important during the early postoperative period.

Healing and recurrence rates were compared in leg ulcers of different aetiology in 385 patients with 406 chronic leg ulcers. Standard treatment was excision of the ulcer followed by meshed split-skin grafting and correction of superficial venous insufficiency in the area. The median age of the patients was 75 years (range 16-95). After one year 345 patients with 357 leg ulcers were alive. Overall healing rate was 64% (227 in 357 legs) after one year. The best results were achieved in traumatic ulcers (31 in 36 ulcers) and worst for the arterial ulcers (4 in 20 ulcers). Recurrence rate in venous and venous/ischaemic ulcers was 14% (33 in 235 legs) and 8% (n=3) in the traumatic ulcers. Vasculitic ulcers tend to recur 59% (n=10), but the graft does relieve pain.

This study followed 115 patients with diabetes--who between them had 140 feet with Charcot's arthropathy--over six to 114 months (median: 48). A total of 43 patients (37%) developed ulcers in 53 feet. Their treatment was multifactorial. An offloading regimen was adopted, with the use of crutches and therapeutic sandals with soft, individually moulded insoles, followed by adjusted or bespoke shoes. Recalcitrant ulcers were treated with surgery in 16 patients (37%). Antibiotics were needed by 21 patients (49%). The incidence of ulceration was 17% per year. The median time interval between the acute component of Charcot's arthropathy and ulcer development was 36 months (range: 0-120 months). In seven patients, the ulcer developed during the acute phase. In 12 patients the ulcers were localised to the rockerbottom deformity in the mid-foot region, but in 31 patients other regions were affected. Dynamic footprint analysis was used to help adjust the offloading shoe/insole on the rockerbottom deformity. Such ulcers took twice as long to heal as other ulcers. Surgical treatment comprised: major amputation (two patients), arthrodesis for unstable ankle (three patients), toe amputations (seven patients), resection of the rockerbottom deformity (one patient) and other revisions (three patients). One patient died with an unhealed ulcer. There is a four-fold risk of ulcers in diabetic Charcot deformity compared with the overall risk of foot ulcers in diabetic feet. Healing was achieved in 40 patients (93%). The surgical intervention rate of 37% in ulcer cases in Charcot feet was low compared with the literature.

Hypothesis Type 1 and type 2 diabetes mellitus and glycemic control influence wound healing in humans. Design Experimental study using a human wound-healing model. Setting Collaboration among a multidisciplinary wound-healing department, department of medicine, and research laboratories. Patients, Control Subjects, and Methods In 34 patients with type 1 (insulin-dependent) and 25 with type 2 (non–insulin-dependent) diabetes and 5 nondiabetic control subjects matched with the type 2 diabetic patients, wound-healing capacity was determined as subcutaneous accumulation of collagen measured as hydroxyproline. Two expanded polytetrafluoroethylene tubes were implanted and removed 10 days later. The hydroxyproline level was determined by means of high-performance liquid chromatography; the collagenase activity, by using a radiolabeled collagen substrate. Proliferation of fibroblasts cultured from the wounds was studied in patient groups. Results The deposition of hydroxyproline decreased by 40% ( P = .03) in type 1 compared with type 2 diabetes (median, 0.70 vs 1.16 nmol/mg; interquartile range, 0.48-1.04 vs 0.56-1.63 nmol/mg), which in turn did not differ significantly from that of controls (median, 1.35 nmol/mg; interquartile range, 0.72-1.88 nmol/mg). The decreased collagen deposition in type 1 diabetes was not caused by increased collagenase activity. The deposition of hydroxyproline did not correlate significantly ( r s = 0.07; P = .63) with glycosylated hemoglobin levels in either diabetic group. Fibroblast growth was also decreased in type 1 compared with type 2 diabetic patients and controls. Conclusions Collagen deposition in acute wounds is impaired in type 1 diabetes, possibly due to a decreased fibroblast proliferation. In type 2 diabetes, collagen deposition is normal. Glycemic control does not influence collagen deposition in acute wound repair in type 1 or in type 2 diabetes mellitus.

Hypothesis An independent, multidisciplinary wound healing center in an accepted national expert function of wound healing is the optimal way to improve prophylaxis and treatment of patients with problem wounds. Design A clinical perspective analysis. Setting An independent, multidisciplinary wound healing center focusing on all types of problem wounds, organized as a university hospital department, and integrated in an expert function in the national health care organization of Denmark. Patients and Methods Patients with all types of problem wounds referred to and treated in the center during the first years of its existence provided a model for a new multidisciplinary structure for treatment of wound patients in the health care system. Results During the first 3 years of the fully functioning wound healing center, a total of 23 802 patient consultations were performed in the outpatient clinic, and 1014 patients with problem wounds were hospitalized in the inpatient ward. The surgical concept of the center has resulted in improved healing rates in patients with leg ulcers and decreased rates of major amputations. The outpatient function has resulted in a decrease in the number of patients transported in beds to the center. This structure provides better opportunities for basic and clinical research as well as for establishing expert education for all types of health care personnel. The center's structure has been the background for establishing an expert function in wound healing, allowing the wound healing area area to be fully integrated in the Danish National Health Care System. Overall, the concept and structure of the center have enhanced the knowledge and understanding of wound problems and increased the status of wound healing and patient care. Conclusions Establishing multidisciplinary centers integrated into an accepted national expert function of wound healing is an optimal way to improve the clinical outcome of prophylaxis and treatment of all types of problem wounds. This model, with minor adjustments, may be applicable for both industrialized and developing countries.

OBJECTIVE: To assess the long-term results after Charcot breakdown with spontaneous onset in diabetic feet. RESEARCH DESIGN AND METHODS: This study was retrospective. A total of 115 patients (140 feet), 107 with acute deformity and 8 with chronic Charcot deformity, were followed for a median of 48 months (range 6-114). The routine treatment for acute cases was a weight-off regimen with crutches and foot protection with therapeutic shoes until skin temperature had normalized followed by increased weightbearing and the use of bespoke shoes or modification of conventional shoes. RESULTS: The incidence of Charcot deformity was 0.3%/year in the diabetic population investigated. About half of the patients were active in their jobs. Major complications were encountered in 5 (4%) of the patients that required surgical intervention: arthrodesis for unstable malaligned ankles in 3 subjects (1 bilaterally) and major amputation in 2 subjects for unstable ankle and pressure sores. Minor complications were recorded in 43% of subjects: new attacks of Charcot breakdown in 41 patients (36%) and/or foot ulceration in 43 patients (37%) that required minor surgical procedures for 11 patients. All healed except in 2 patients: 1 patient died before the Charcot fractures had healed, and 1 patient died with an unhealed ulcer. No patient lost the ability to walk independently. CONCLUSIONS: Major surgical procedures in only 4% were particularly related to patients with Charcot deformities in the ankle. Minor complications were recorded in about half of the patients. Lifelong foot care is required for diabetic patients with Charcot feet.

The outcome of percutaneous transluminal angioplasty (PTA) was evaluated for treatment of 87 limbs with femoropopliteal stenoses, including 55 short stenoses (2.4 +/- 1.6 cm, mean +/- SD), seven single long stenoses (10.4 +/- 2.0 cm), and 25 multifocal stenoses (2.1 +/- 1.6 cm), where two to four separate segments were dilated. Following 98% initial technical success, 3-year patency was 68% for single short stenoses, as opposed to 20% for long and multifocal stenoses (p = 0.05, logrank test). Antiplatelet therapy with acetylsalicyclic acid was not found to influence occurrence of restenosis. The study documents the poor PTA results for long and multifocal stenoses and suggests precautions to be taken during PTA in order to minimize the area of artery wall damage.

To determine the influence of ulcer location on ulcer healing in diabetic foot disease, as especially heel ulcers are considered poorly healing ulcers.

Compare the recanalization rate of femoropopliteal occlusions between movable core wire guide (MG) and hydrophilic guidewire (HG).Conventional PTA technique was used, followed by enclosed thrombolysis. The MG was used for all patients in the first 2 years, the HG in the following 2 years. Baseline characteristics were similar for the two groups of patients.Recanalization of 124 femoropopliteal occlusions was attempted. Technical success was achieved with the MG in 45 of 59 procedures; 42 procedures were clinically successful. Using the HG, technical success was achieved in 35 of 65 procedures; clinical success was achieved in 35 of 65 procedures; clinical success was achieved in 29 cases (p0.0048). At 1-year follow-up, 32 extremities improved after treatment with MG and 22 extremities after treatment with HG (p0.035).The results suggest that the MG should be the first choice in recanalization of femoropopliteal occlusions.

A retrospective review of amputations in patients with vascular disease during 10 years in Bispebjerg Hospital was undertaken. There were 1383 amputations leading to 1167 final level amputations. In previously independent patients there were 482 below knee amputations (BKA), 476 above knee amputations (AKA) and 43 had disarticulations in the ankle, knee or hip. During the period studied the number of final level amputations in independent patients were halved from 122 in 1981 to 58 in 1990. A similar reduction was also found in the total number of amputations: from 171 to 90, and in the number of reamputations: from 35 to 21. However, amputations in patients from long stay institutions remained at a constant level by on average 17 per year. The decrease in amputation rate took place synchronously with an increasing use of bypass to crural and pedal arteries as well as an overall increase in vascular reconstructions and angioplasties of more than 100%. However, the BKA/AKA ratio decreased from 1.12 to 0.67 (p0.005).

Segmentally enclosed thrombolysis (SET) was performed immediately following 34 percutaneous transluminal angioplasties (PTAs) for femoropopliteal occlusions. The dilated segment was sealed off with a double balloon catheter, and recombinant tissue plasminogen activator (rt-PA) 1 mg/ml and heparin 200 IU/ml were injected between the balloons. The catheter was removed after 30 min and heparin treatment was continued for 24 h. Alpha-2-antiplasmin was initially reduced by 13% and normalized 2 h after SET, indicating that only small amounts of free plasmin were liberated during thrombolysis. No clinically relevant changes in plasma fibrinogen occurred. Two puncture site hemorrhages did not coincide with the coagulopathy induced by SET. One-year patency was 80%. Early rethrombosis occurred in 9% versus 41% in our previous series on standard PTA for femoropopliteal occlusions (p less than 0.001). Therefore, SET is considered beneficial in reducing the incidence of early rethrombosis.

Lower-extremity amputation for arterial insufficiency was performed in 282 cases ineligible for vascular surgery. In 203 cases (Group I), amputation was elective without previous vascular surgery. In 14 cases (Group II), amputation followed recent vascular reconstruction, and in 12 cases (Group III) amputation was performed after failed thromboembolectomy. In 53 cases (Group IV), amputation was done acutely, i.e., as a life-saving procedure because of septicemia. The results as regards both knee salvage and survival were much better in Groups I and II than in Groups III and IV. We conclude that knee salvage is poor and mortality high after acute amputations and after failed thrombembolectomy. These factors should be taken into account when comparing series from different centers.

In 102 leg amputations for arterial occlusion including 84 below-knee (BK), 16 above-knee (AD) 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 less than 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 less than 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.

The recent development of a mobile 10 detector unit, using i.v. Xenon-133 technique, has made it possible to perform repeated bedside measurements of cerebral blood flow (CBF). Test-retest studies were carried out in 38 atherosclerotic subjects, in order to evaluate the reproducibility of CBF level and side-to-side asymmetry. Data were analysed according to the Obrist model and the results compared with those obtained using a model correcting for the air passage artifact. Reproducibility was of the same order of magnitude as reported using stationary equipment. The side-to-side CBF asymmetry was considerably more reproducible than CBF level. Using a single detector instead of five regional values averaged as the hemispheric flow increased standard deviation of CBF level by 10-20%, while the variation in asymmetry was doubled. In optimal measuring conditions the two models revealed no significant differences, but in low flow situations the artifact model yielded significantly more stable results. The present apparatus, equipped with 3-5 detectors covering each hemisphere, offers the opportunity of performing serial CBF measurements in situations not otherwise feasible.

This paper is devoted to elucidation of the question: Which external pressure is required to stop skin blood flow at the skin - support interface in humans lying on the back in the supine position? Cessation of blood flow was recorded as cessation of washout of an intracutaneous depot of 131I--antipyrine mixed with histamine. The external pressure was measured by a small airfilled plastic cushion connected to a mercury manometer. In 11 normal subjects, eight patients with hypertension and seven patients with tetra- or paraplegia the “flow cessation external pressure” (FCEP) was strongly correlated to the auscultatory brachial mean blood pressure (p>0.001). The difference mean blood pressure - FCEP was on average 4 mmHg (range (− 11) - (” 20) mmHg) and there was no significant difference between the three groups studied. Thus external pressure exceeding the actual mean blood pressure will stop skin circulation.

The skin perfusion pressure was measured as the external pressure required to stop blood flow, as evidenced by cessation of the washout of an intracutaneous depot of [131I-]antipyrine mixed with histamine. The external pressure on the skin was measured by an 11 x 11 cm slack air-filled plastic cushion connected to a mercury manometer and interposed between the labelled area and a blood pressure cuff. The 'flow cessation external pressure' (FCEP) varied parallel to the intra-arterial femoral mean blood pressure, but was on the average 10.8 mmHg (SD 6.4) lower. FCEP was measured on twenty normal subjects at four different segments of the leg. The average differences between auscultatory brachial mean blood pressure and FCEP were: thigh 12.0 mmHg (SD 7.6); calf 10.4 mmHg (SD 7.4); ankle 12.9 mmHG (SD 10.1); foot 20.2 mmHg (SD 12.1). The SD of the difference between measurements on two different days, performed in forty-four patients with different degrees of occlusive arterial disease, varied between 5.6 and 8.3 mmHg at the different levels. The present data indicate that the skin perfusion pressure on the legs in normal subjects lies approximately 10 mmHg lower than the systemic mean arterial blood pressure.