Factors Influencing the Risk of Major Amputation in Patients with Diabetic Foot Ulcers Treated by Autologous Cell Therapy.

Introduction: Autologous cell therapy (ACT) is one of the last options for limb salvage in patients with chronic limb-threatening ischemia (CLTI) and diabetic foot ulcers (DFU). However, some patients may still undergo a major amputation even after ACT, but the risk factors for this are not known. Therefore, the aim of our study was to assess the risk factors for major amputation in patients with CLTI and DFU during a 2-year follow-up after ACT. Methods: One hundred and thirteen patients after ACT were included in our study and divided into two groups: Group 1 with major amputation (AMP; n = 37) and Group 2 without amputation (nAMP, n = 76). The risk factors for major amputation were evaluated before ACT and included factors relating to the patient, the DFU, and the cell product. Results: The AMP group had significantly higher C-reactive protein (CRP) levels compared to the nAMP group (22.7 vs. 10.7 mg/L, p = 0.024). In stepwise logistic regression, independent predictors for major amputation were mutation of the gene for methylenetetrahydrofolate reductase (MTHFR) with heterozygote and homozygote polymorphism 1298 (OR 4.33 [95% CI 1.05-17.6]), smoking (OR 3.83 [95% CI 1.18-12.5]), and CRP > 10 mg/L (OR 2.76 [95% CI 0.93-8.21]). Lower transcutaneous oxygen pressure (TcPO2) values were observed in AMP patients compared to the nAMP group at one month (24.5 vs. 33.2, p = 0.012) and at 3 months (31.1 vs. 40.9, p = 0.009) after ACT. Conclusion: Our study showed that the risk for major amputation after ACT in patients with CLTI and DFU is increased by the presence of MTHFR heterozygote and homozygote gene mutations, smoking, and higher CRP at baseline. Lower TcPO2 at one and 3 months after ACT may also have a predictive value. Therefore, it is necessary to stop smoking before ACT, treat any infection, and, above all, consider antiaggregation or anticoagulant treatment after the procedure.

Incidence and Risk Factors of Diabetic Foot Syndrome in Patients Early After Pancreas or Kidney/Pancreas Transplantation and its Association with Preventive Measures.

Diabetic foot (DF) can develop in diabetic patients after organ transplantation (Tx) due to several factors including peripheral arterial disease (PAD), diabetic neuropathy and inappropriate DF prevention. Aim: To assess the occurrence of DF and associated risk factors in transplant patients. Methods: Fifty-seven diabetic patients were enrolled as part of this prospective study. All patients underwent organ Tx (01/2013-12/2015) and were followed up for minimum of 12 months up to a maximum of 50 months. Over the study period we evaluated DF incidence and identified a number of factors likely to influence DF development, including organ function, presence of late complications, PAD, history of DF, levels of physical activity before and after Tx, patient education and standards of DF prevention. Results: Active DF developed in 31.6% (18/57) of patients after organ Tx within 11 months on average (10.7 ± 8 months). The following factors significantly correlated with DF development: diabetes control (p = .0065), PAD (p<0.0001), transcutaneous oxygen pressure (TcPO2;p = .01), history of DF (p = .0031), deformities (p = .0021) and increased leisure-time physical activity (LTPA) before Tx (p = .037). However, based on logistic stepwise regression analysis, the only factors significantly associated with DF during the post-transplant period were: PAD, deformities and increased LTPA. Education was provided to patients periodically (2.6 ± 2.5 times) during the observation period. Although 94.7% of patients regularly inspected their feet (4.5 ± 2.9 times/week), only 26.3% of transplant patients used appropriate footwear. Conclusions: Incidence of DF was relatively high, affecting almost 1/3 of pancreas and kidney/pancreas recipients. The predominant risk factors were: presence of PAD, foot deformities and higher LTPA before Tx. Therefore, we recommend a programme involving more detailed vascular and physical examinations and more intensive education focusing on physical activity and DF prevention in at-risk patients before transplantation.

Clinical and (31)P magnetic resonance spectroscopy characterization of patients with critical limb ischemia before and after autologous cell therapy.

Autologous cell therapy (ACT) is a new treatment method for diabetic patients with critical limb ischemia (CLI) not eligible for standard revascularization. After intramuscular injection of bone marrow-derived mononuclear cells local arteriogenesis in the ischemic tissue occurs. Studies assessing visualization of this therapeutic vasculogenesis after ACT by novel imaging techniques are lacking. The aim of our study was to assess the effect of ACT on possible metabolic changes and perfusion of critically ischemic limbs using (31)P magnetic resonance spectroscopy ( (31)P MRS) and its possible correlation with changes of transcutaneous oxygen pressure (TcPO(2)). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO(2) as well as rest (phosphocreatine, adenosine triphosphate and inorganic phosphate) and dynamic (mitochondrial capacity and phosphocreatine recovery time) (31)P-MRS parameters were evaluated at baseline and 3 months after cell treatment. TcPO(2) increased significantly after 3 months compared with baseline (from 22.4±8.2 to 37.6±13.3 mm Hg, p=0.0002). Rest and dynamic (31)P MRS parameters were not significantly different after ACT in comparison with baseline values. Our study showed a significant increase of TcPO(2) on the dorsum of the foot after ACT. We did not observe any changes of rest or dynamic (31)P MRS parameters in the area of the proximal calf where the cell suspension has been injected into.

Impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia.

AIM: To assess the impact of autologous cell therapy on critical limb ischaemia in people with diabetes and diabetic kidney disease. METHODS: A total of 59 people with diabetes (type 1 or type 2) and critical limb ischaemia, persisting after standard revascularization, were treated with cell therapy in our foot clinic over 7 years; this group comprised 17 people with and 42 without severe diabetic kidney disease. The control group had the same inclusion criteria, but was treated conservatively and comprised 21 people with and 23 without severe diabetic kidney disease. Severe diabetic kidney disease was defined as chronic kidney disease stages 4-5 (GFR <30 ml/min/1.73 m²). Death and amputation-free survival were assessed during the 18-month follow-up; changes in transcutaneous oxygen pressure were evaluated at 6 and 12 months after cell therapy. RESULTS: Transcutaneous oxygen pressure increased significantly in both groups receiving cell therapy compared to baseline (both P<0.01); no significant change in either of the control groups was observed. The cell therapy severe diabetic kidney disease group had a significantly longer amputation-free survival time compared to the severe diabetic kidney disease control group (hazard ratio 0.36, 95% CI 0.14-0.91; P=0.042); there was no difference in the non-severe diabetic kidney disease groups. The severe diabetic kidney disease control group had a tendency to have higher mortality (hazard ratio 2.82, 95% CI 0.81-9.80; P=0.062) than the non-severe diabetic kidney disease control group, but there was no difference between the severe diabetic kidney disease and non-severe diabetic kidney disease cell therapy groups. CONCLUSIONS: The present study shows that autologous cell therapy in people with severe diabetic kidney disease significantly improved critical limb ischaemia and lengthened amputation-free survival in comparison with conservative treatment; however, the treatment did not influence overall survival.

Detection and quantitation of iron in ferritin, transferrin and labile iron pool (LIP) in cardiomyocytes using 55Fe and storage phosphorimaging.

Dysregulated iron metabolism has a detrimental effect on cardiac function. The importance of iron homeostasis in cardiac health and disease warrants detailed studies of cardiomyocyte iron uptake, utilization and recycling at the molecular level. In this study, we have performed metabolic labeling of primary cultures of neonatal rat cardiomyocytes with radioactive iron coupled with separation of labeled iron-containing molecules by native electrophoresis followed by detection and quantification of incorporated radioiron by storage phosphorimaging. For the radiolabeling we used a safe and convenient beta emitter 55Fe which enabled sensitive and simultaneous detection and quantitation of iron in cardiomyocyte ferritin, transferrin and the labile iron pool (LIP). The LIP is believed to represent potentially dangerous redox-active iron bound to uncharacterized molecules. Using size-exclusion chromatography spin micro columns, we demonstrate that iron in the LIP is bound to high molecular weight molecule(s) (≥5000 Da) in the neonatal cardiomyocytes.

Perfusion scintigraphy in the assessment of autologous cell therapy in diabetic patients with critical limb ischemia.

Perfusion scintigraphy with technetium-99-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) is often used for assessing myocardial function but the number of studies concerning lower limb perfusion is limited. The aim of our study was to assess whether (99m)Tc-MIBI was an eligible method for evaluation of the effect of cell therapy on critical limb ischemia (CLI) in diabetic patients. (99m)Tc-MIBI of calf muscles was performed before and 3 months after autologous cell therapy (ACT) in 24 diabetic patients with CLI. Scintigraphic parameters such as rest count and exercising count after a stress test were defined. These parameters and their ratios were compared between treated and untreated (control) limbs and with changes in transcutaneous oxygen pressure (TcPO(2)) that served as a reference method. The effect of ACT was confirmed by a significant increase in TcPO(2) values (p<0.001) at 3 months after ACT. We did not observe any significant changes of scintigraphic parameters both at rest and after stress 3 months after ACT, there were no differences between treated and control limbs and no association with TcPO(2) changes. Results of our study showed no significant contribution of (99m)Tc-MIBI of calf muscles to the assessment of ACT in diabetic patients with CLI over a 3-month follow-up period.

Minor amputation does not negatively affect health-related quality of life as compared with conservative treatment in patients with a diabetic foot ulcer: An observational study.

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.

Neonatal capsaicin administration impairs postnatal development of the cardiac chronotropy and inotropy in rats.

The present study evaluated the impact of neonatal administration of capsaicin (neurotoxin from red hot pepper used for sensory denervation) on postnatal development of the heart rate and ventricular contractility. In the rats subjected to capsaicin administration (100 mg/kg) on postnatal days 2 and 3 and their vehicle-treated controls at the ages of 10 to 90 days, function of the sympathetic innervation of the developing heart was characterized by evaluation of chronotropic responses to metipranolol and atropine, norepinephrine concentrations in the heart, and norepinephrine release from the heart atria. Sensory denervation was verified by determination of calcitonin gene-related peptide levels in the heart. Direct cytotoxic effects of capsaicin were assessed on cultured neonatal cardiomyocytes. Capsaicin-treated rats displayed higher resting heart rates, lower atropine effect, but no difference in the effect of metipranolol. Norepinephrine tissue levels and release did not differ from controls. Contraction force of the right ventricular papillary muscle was lower till the age of 60 days. Significantly reduced viability of neonatal cardiomyocytes was demonstrated at capsaicin concentration 100 micromol/l. Our study suggests that neonatal capsaicin treatment leads to impaired maturation of the developing cardiomyocytes. This effect cannot be attributed exclusively to sensory denervation of the rat heart since capsaicin acts also directly on the cardiac cells.

[Special contact splints in postoperative care for patients with the diabetic foot]. / Pouzití speciálních kontaktních dlah v pooperacní péci u syndromu diabetické nohy.

UNLABELLED: Adequate stabilization and off-loading of the lower limb is an integral part of postoperative care for patients with the diabetic foot. Off-loading can accelerate the healing process and reduce the number of complications and reoperations. The newly introduced method of the performance of removable contact splints (modified contact removable casts) seems to fulfil a number of requirements for stabilization and off-loading devices - the method is safe and can actually reduce the healing time and the number of reoperations in patients with the diabetic foot. KEY WORDS: diabetic foot - off-loading - splints.

Importance of factors determining the low health-related quality of life in people presenting with a diabetic foot ulcer: the Eurodiale study.

AIM: To identify the factors responsible for the low health-related quality of life associated with foot ulcers and the relative importance of these factors. METHODS: A 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. RESULTS: Patients 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. CONCLUSIONS: The 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.

Both autologous bone marrow mononuclear cell and peripheral blood progenitor cell therapies similarly improve ischaemia in patients with diabetic foot in comparison with control treatment.

BACKGROUND: The aim of our study was to compare the effect of bone marrow mononuclear cell and peripheral blood progenitor cell therapies in patients with diabetic foot disease and critical limb ischaemia unresponsive to revascularization with conservative therapy. METHODS: Twenty-eight patients with diabetic foot disease (17 treated by bone marrow cells and 11 by peripheral blood cell) were included into an active group and 22 patients into a control group without cell treatment. Transcutaneous oxygen pressure and rate of major amputation, as the main outcome measures, were compared between bone marrow cells, peripheral blood cell and control groups over 6 months; both cell therapy methods were also compared by the characteristics of cell suspensions. Possible adverse events were evaluated by changes of serum levels of angiogenic cytokines and retinal fundoscopic examination. RESULTS: The transcutaneous oxygen pressure increased significantly (p < 0.05) compared with baseline in both active groups after 6 months, with no significant differences between bone marrow cells and peripheral blood cell groups; however, no change of transcutaneous oxygen pressure in the control group was observed. The rate of major amputation by 6 months was significantly lower in the active cell therapy group compared with that in the control group (11.1% vs. 50%, p = 0.0032), with no difference between bone marrow cells and peripheral blood cell. A number of injected CD34+ cells and serum levels of angiogenic cytokines after treatment did not significantly differ between bone marrow cells and peripheral blood cell. CONCLUSIONS: Our study showed a superior benefit of bone marrow cells and peripheral blood cell treatments of critical limb ischaemia in patients with diabetic foot disease when compared with conservative therapy. There was no difference between both cell therapy groups, and no patient demonstrated signs of systemic vasculogenesis.

[Adherence to the international guidelines on the treatment of diabetic leg syndrome--options available in the Czech Republic]. / Moznosti plnení mezinárodních doporucení terapie syndromu diabetické nohy v Ceské republice.

Possibilities of fulfilling of the practical guidelines on the management of the diabetic foot in the Czech Republic are limited by lack of experts and specialized place of work in podiatry, inconsiderable are economic problems, too. Foot care is of highest quality when is directed by a multidisciplinary foot team. In the Czech Republic, there is an urgent need for podiatry training programme and foot clinic support. Investing in diabetic foot programme can be one of the most cost-effective forms of healthcare expenditure, provided the programme is goal-focused and properly implemented. Paper deal with key points of the podiatry programme--organization, health care education and effective prevention and risk patients follow-up, rational surgical treatment and foot infection management, extension of up-to-date methods of PAD treatment, and effective economic approach to foot care especially considering DRG system during hospitalization.

[Treatment of critical limb ischemia and diabetic foot disease by the use of autologous stem cells]. / Terapie kritické koncetinové ischemie u pacientu se syndromem diabetické nohy pomocí autologních kmenových bunek.

AIM: The aim of our study was to assess safety and effectiveness of therapy of critical limb ischaemia by autologous stem cells and evaluation of potential adverse events. METHODS: Fourteen patients were included into the study (11 men, 3 women, mean age 61.9 +/- 9.6 years, mean diabetes duration 23.5 +/- 11.1 years, mean glycated hemoglobin 6 +/- 1%). Eight patients were treated by bone marrow stromal cells, 6 patients by peripheral blood progenitor cells after stimulation by filgrastim. The suspension of stem cells was then applied into the muscles of ischemic limbs. We evaluated transcutaneous oxygen tension (TcPO2), subjective pain sensation assessed by Visual Analog Scale (VAS) and wound healing. RESULTS: TcPO2 significantly increased in all patients from 10 +/- 8.7 mm Hg before the treatment to 39.4 +/- 9.5 mm Hg after 6 months (p = 0.0005) after stem cell therapy. We also observed significant area defect reduction and pain decrease during the follow-up period. Median of area defect was reduced from 4.3 (0.7 - 31.7) before the treatment to 0.06 (0 - 0.5) cm2 after 6 months from the treatment (p = 0.0078). Decrease in rest pain was observed in all patients, mean VAS decreased from 5.3 +/- 1.8 to 1.1 +/- 1.3 after 6 months (p = 0.002). CONCLUSION: Our study suggests that stem cell therapy of diabetic foot disease is an effective therapeutic option with no adverse events for patients with severe peripheral arterial disease. This treatment leads to increase of transcutaneous oxygen tension, improves wound healing and decreases the rest pain.

Differences in minor amputation rate in diabetic foot disease throughout Europe are in part explained by differences in disease severity at presentation.

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.

Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale Study.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: 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.

[Education of diabetic patients with chronic kidney disease and after transplantation]. / Edukace diabetiku v renálním selháni a po transplantaci.

Despite recent advances in the management of diabetes, diabetic nephropathy is the most frequent cause ofend-stage renal disease. Even when diabetic nephropathy is established, patient's care should be optimized to delay progression of nephropathy or other diabetic complications. Evidence exists for the effectiveness of diet intervention, blood pressure and diabetes control and treatment of metabolic syndrome. We emphasize the need for closer co-operation not only between diabetologists, primary care physicians and nephrologists, but with educated diabetic patients, too. At referral to nephrologist, many patients' care is suboptimal and referral is too late. The most important education information for patients is to stick to diet and keep adequate blood pressure and diabetes control with self-monitoring. Effectiveness of each of these recommendations is critically assessed. Patients after kidney or combined kidney and pancreas transplantation have to be educated mainly in symptoms of rejection and diabetic foot care. They are recommended to take regularly the prescribed medicines, to distinguish the adverse events of immunosuppression and keep all doctor's appointments.

Delivery of care to diabetic patients with foot ulcers in daily practice: results of the Eurodiale Study, a prospective cohort study.

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.

Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study.

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.

[Examination of tactile disorders in diabetic patients and cooperation with a neurologist]. / Vyletfení taktilních poruch u diabetiku a spolupráce s neurologem.

Examining sensorial dysfunction may be difficult for both the doctor and the patient because subjective feelings are misleading and do not reflect the actual severity of a neurological disorder. Sensorial tests provide objective results of measurements, which can be checked against normal values and which allow for determining the severity of neuropathy. Examining sensorial function on feet is necessary in diabetic patients because its loss is the principal risk factor for ulceration. The examination comprises vibration perception tests using a tuner or a biothesiometer, and evaluating surface sensation with the use of monofilaments. A more detailed type of examination is the testing of the electric current perception threshold with the use of different models of neurometer which allows for examining all three main groups of sensorial nerve fibres, i.e. Abeta (large myelinated), Agamma (small myelinated) and C (non-myelinated). The study evaluated the differences between routine diagnosing of polyneuropathy on outpatient basis and biothesiometer and monofilament examination. We discovered that patients with severe neuropathy diagnosed by non-invasive semi-quantitative examination were diagnosed for neuropathy on outpatient basis only in 54% of cases, which points to the need to extend the use of non-invasive examination to outpatient practice. The Neuropathy Disability Score (NDS) assesses neurological functions as a whole, but is more time consuming than simple sensorial tests. Neuropathy self-monitoring by the patient in risk of diabetic foot using the diagnostic test (Neuropad) looks promising. The diabetologist cooperates with a neurologist especially in differential diagnosis of neuropathy, in the treatment of its painful forms and in the classification of its severity.

High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study.

AIMS/HYPOTHESIS: 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. METHODS: 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 +. RESULTS: 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. CONCLUSIONS/INTERPRETATION: 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.