Search

The care of patients with diabetic foot syndrome (DFS) requires interdisciplinary cooperation, and therefore interdisciplinary recommendations focused on the diagnosis and treatment and prevention of DFS are in place. We also need these recommendations because DFS has its own specifics that affect its diagnosis, therapy, but also the prognosis of patients. These include, for example, the different course of infection and PAD in patients with diabetes, the diagnosis of neuropathic Charcot osteoarthropathy, and the frequent association with end stage kidney disease, which worsens the course of SDN and increases its risk. Last but not least, the specifics of DFS include the issue of amputations with a significantly worse prognosis than in people without diabetes. The creation of an interdisciplinary team in foot clinics, providing comprehensive care for patients with DFS according to the recommended procedure, is associated with improved prognosis of patients with DFS, especially the reduction of amputations.

Scoring for the risk of Diabetic foot syndrome (DFS) should be performed regularly in each patient with diabetes mellitus (DM). Patients at risk for DFS should be followed by diabetologists, those with moderate and severe risk for the development of DFS or those with DFS in remission should be already followed by podiatrists. The aim of our study was to determine the extent of DFS risk screening procedures, dispensary care of patients at risk for DFS and treatment of patients with newly developed DFS in diabetes clinics in the Czech Republic.To find out the study data, we prepared in cooperation with the#268;DS#268;LS JEP Committee a questionnaire survey for outpatient diabetology specialists.The questionnaire was completed by 57% (76/135) of diabetologists. Most of them dispensary approximately 1000- 2000 patients with DM. Their feet are checked by 98.7% of diabetologists (1.6 ± 0.8 times a year on average). Screening for the risk of DFS (13024) is performing in less than 100 patients by 74.3% of diabetologists, in 100-200 patients by 14.9% and in more than 200 patients by 10.8% of diabetologists. 77% of respondents are able to examine neuropathy, the rest send their patients to neurologists, peripheral arterial disease is evaluated by only 47.3% of diabetologists (35.3% of them use some form of instrumental examination), others (48.6%) send patients to angiologists, 4.1% of diabetologists do not examine PAD at all). Based on the assessed findings, more than half of the respondents (50.7%) perform scoring for the risk of DFS, but 1/5 of outpatient diabetologists do not know how the scoring is performed. If colleagues find a patient at a risk for DFS, they usually follow him/her by themselves (64.4%), in 24.6% of cases they send the patient immediately to podiatry or surgery (11%). If a patient with a new DFS comes at diabetology clinic, 72.6% of diabetologists are able to prescribe off-loading, 60.3% antibiotics, 47.9% local therapy. Only 52.1% of diabetologists send a patient with a new DFS to outpatient foot clinic, 39.7% to surgery, the rest of them elsewhere.Based on the questionnaire survey results, the screening of DFS is currently severely undersized in outpatient diabetology clinics, it is sufficiently performed only by 11% of diabetologists. Only 16% of diabetologists perform some form of non-invasive diagnostic procedures detecting peripheral arterial disease, neuropathy examinations are more common. If a diabetologist meet a patient with newly developed DFS, he/she is able to prescribe off-loading or antibiotics, but only half of the diabetologists send the patient to outpatient foot clinic, probably due to a lack of them or their overload.

Autologous cell therapy (ACT) is a new treatment for patients with no-option critical limb ischemia (NO-CLI). We evaluated the factors involved in the nonresponse to ACT in patients with CLI and diabetic foot. Diabetic patients (n = 72) with NO-CLI treated using ACT in our foot clinic over a period of 8 years were divided into responders (n = 57) and nonresponders (n = 15). Nonresponder was defined as an insufficient increase in transcutaneous oxygen pressure by

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 (TcPO2). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO2 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. TcPO2 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 TcPO2 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.

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

Infections caused by Pseudomonas sp are difficult to resolve by antibiotics (ATBs) and local therapy. The aim of our pilot study was to assess the effect of different local agents—particularly acidifying solutions—on the healing of diabetic foot ulcers (DFUs), eradication of pathogens, and economic costs related to DFU therapy. In this case study, we monitored 32 DFU patients infected by Pseudomonas species. Patients were divided into 2 groups according to the local therapy provided: group 1 (n = 15)—modern local treatment; group 2 (n = 17)—acidifying antiseptic solutions. The study groups differed only with regard to ATB usage prior to enrolment in the study ( P = .004), but did not differ with regard to age, diabetes control, peripheral arterial disease, or microcirculation status. During the follow-up period, DFUs healed in 20% of cases in group 1, but there were no cases of healing in group 2 (NS). The length of ATB therapy, the number of new osteomyelitis, lower limb amputations, and the changes of DFUs status/proportions did not differ significantly between study groups. Pseudomonas was eradicated in 67% of cases in group 1 and in 65% of cases in group 2. The local treatment given to group 2 patients was associated with lower costs ( P < .0001). Conclusion. Acidifying agents had the same effect as modern healing agents on wound healing, the number of amputations, and the eradication of Pseudomonas. Moreover, therapy performed using acidifying solutions proved in our pilot study markedly cheaper.

Endothelial progenitors are a population of cells with the inherent capacity to differentiate into mature endothelial cells and proangiogenic paracrine action. These characteristics have led to extensive studies being performed and tested in the treatment of tissue ischemia. The natural course of diabetes mellitus (DM) results in multiple areas of vascular damage. Thus endothelial progenitor cells'(EPCs) beneficial potential is particularly desirable in diabetic patients. In this review, we summarize contemporary knowledge of EPC biology in DM. It has been shown that EPC functions are considerably impaired by DM. The presence of peripheral arterial disease (PAD) seems to further exacerbate the deficiencies of EPCs. However, studies examining EPC counts in PAD and DM observed disparate results, which can be due to a lack of consensus on precise EPC immunotype used in the different studies. Nevertheless, the results of EPC-based autologous cell therapy (ACT) are promising. In addition, EPCs have been shown to bean independent predictor of cardiovascular risk and diabetic foot ulcer healing.

Background: Autologous cell-therapy (ACT) is a new treatment method for patients with diabetes and no-option chronic limb-threatening ischemia (NO-CLTI). We aimed to assess the impact of ACT on CLTI in comparison with standard treatment (ST) in a randomized controlled trial. Methods: Forty diabetic patients with NO-CLTI were randomized to receive either cell therapy (n=20) or standard conservative therapy (n=16); 4 patients dropped out of the study. After 3 months, those in the ST group were switched to ACT (cell therapy crossover). The effect on ischemia and diabetic foot was assessed by changes in transcutaneous oxygen pressure (TcPO2) and the number of healed patients at 3 months. Amputation rates and amputation-free survival (AFS) were assessed at 3 months and then during 12-month follow-up. Results: TcPO2 increased significantly in the ACT group after 1 and 3 months (both p Conclusions: Our study showed that ACT in patients with no-option CLTI and diabetic foot significantly improved limb ischemia and wound healing when compared to standard conservative therapy, without influencing amputation rates and with a trend to higher 1-year AFS in comparison with delayed ACT treatment in ST group. Disclosure M. Dubsky: None. R. Bem: None. A. Nemcova: None. J. Husáková: None. V. Fejfarova: None. A. Jirkovska: None. K. Sutoris: None. Funding Ministry of Health of the Czech Republic (16-27262A, 00023001)

Background: Autologous cell therapy (ACT) is the last option for patients with no-option chronic limb-threatening ischemia (NO-CLTI) and severe pain. The aim of our study was to assess the impact of ACT on a patient’s quality of life, chronic pain and depression using standardized questionnaires. Methods: Forty patients with NO-CLTI were randomized and divided into groups treated initially with ACT (iACT, n=20) or standard conservative therapy (iST, n=16); 4 patients dropped out of the study. After 3 months, those in the standard therapy (ST) group were switched to (cell therapy crossover). All patients filled out the standardized EQ-5D questionnaire assessing their quality of life. Pain was evaluated using a special questionnaire including the Visual Analogue Scale (VAS) and Wong-Baker Faces (WB). The questionnaires were evaluated before randomization; in the iST group at 3 months after ST and then at 3 months after ACT. Results: Pain was significantly reduced in the iACT group after 3 months compared to baseline in both VAS and WB scores (both p Conclusion: Our study showed significant pain reduction in NO-CLTI patients after ACT; this treatment also led to a decrease in depression rate and overall improvement in their quality of life. Disclosure J. Husáková: None. R. Bem: None. A. Nemcova: None. V. Fejfarova: None. A. Jirkovska: None. M. Dubsky: None. Funding Ministry of Health of the Czech Republic (16-27262A); Project for Development of Research Organization (00023001); IKEM, Prague, Czech Republic

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 (p2;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.

The standard method for assessment of effect of revascularization in patients with diabetic foot (DF) and critical limb ischemia (CLI) is transcutaneous oxygen pressure (TcPO2). Phosphorus magnetic resonance spectroscopy (31P MRS) enables to evaluate oxidative muscle metabolism that could be impaired in patients with diabetes and its complications. The aim of our study was to compare MRS of calf muscle between patients with DF and CLI and healthy controls and to evaluate the contribution of MRS in the assessment of the effect of revascularization.Thirty-four diabetic patients with DF and CLI treated either by autologous cell therapy (ACT; 15 patients) or percutaneous transluminal angioplasty (PTA; 12 patients) in our foot clinic during 2013-2016 and 19 healthy controls were included into the study. TcPO2 measurement was used as a standard method of non-invasive evaluation of limb ischemia. MRS examinations were performed using the whole-body 3T MR system 1 day before and 3 months after the procedure. Subjects were examined in a supine position with the coil fixed under the m. gastrocnemius. MRS parameters were obtained at rest and during the exercise period. Rest MRS parameters of oxidative muscle metabolism such as phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiesters (PDE), adenosine triphosphate (ATP), dynamic MRS parameters such as recovery constant PCr (τPCr) and mitochondrial capacity (Qmax), and pH were compared between patients and healthy controls, and also before and 3 months after revascularization.Patients with CLI had significantly lower PCr/Pi (p0.001), significantly higher Pi and pH (both p0.01), significantly lower Qmax and prolonged τPCr (both p0.001) in comparison with healthy controls. We observed a significant improvement in TcPO2 at 3 months after revascularization (from 26.4 ± 11.7 to 39.7 ± 17.7 mm Hg, p0.005). However, the rest MRS parameters did not change significantly after revascularization. In individual cases we observed improvement of dynamic MRS parameters. There was no correlation between MRS parameters and TcPO2 values.Results of our study show impaired oxidative metabolism of calf muscles in patients with CLI in comparison with healthy controls. We observed an improvement in dynamic MRS parameters in individual cases; this finding should be verified in a large number of patients during longer follow-up.Key words: autologous cell therapy - critical limb ischemia - diabetic foot - MR spectroscopy.

In this review we report on the state of cell therapy of critical limb ischemia (CLI) with respect to differences between diabetic and non-diabetic patients mainly from the clinical point of view. CLI is the most severe form of peripheral arterial disease and its diagnosis and treatment in diabetic patients is very difficult. The therapeutic effect of standard methods of CLI treatment is only partial - more than one third of diabetic patients are not eligible for standard revascularization; therefore, new therapeutic techniques such as cell therapy have been studied in clinical trials. Presence of CLI in patients with diabetic foot disease is associated with worse clinical outcomes such as lack of healing of foot ulcers, major amputations and premature mortality. A revascularization procedure cannot be successful as the only method in contrast to patients without diabetes, but it must always be part of a complex therapy focused not only on ischemia, but also on treatment of infection, off-loading, metabolic control of diabetes and nutrition, local therapy, etc. Therefore, the main criteria for cell therapy may vary in diabetic patients and non-diabetic persons and results of this treatment method should always be assessed in the context of ensuring comprehensive therapy. This review carries out an analysis of the source of precursor cells, route of administration and brings a brief report of published data with respect to diabetic and non-diabetic patients and our experience with autologous cell therapy of diabetic patients with CLI. Analysis of the studies in terms of diabetes is difficult, because in most of them sub-analysis for diabetic patients is not performed separately. The other problem is that it is not clear if diabetic patients received adequate complex treatment for their foot ulcers which can strongly affect the rate of major amputation as an outcome of CLI treatment.

Infections caused by Pseudomonas sp are difficult to resolve by antibiotics (ATBs) and local therapy. The aim of our pilot study was to assess the effect of different local agents-particularly acidifying solutions-on the healing of diabetic foot ulcers (DFUs), eradication of pathogens, and economic costs related to DFU therapy. In this case study, we monitored 32 DFU patients infected by

Objective. Off-loading is one of the crucial components of diabetic foot (DF) therapy. However, there remains a paucity of studies on the most suitable off-loading for DF patients under postoperative care. The aim of our study was to evaluate the effect of different protective off-loading devices on healing and postoperative complications in DF patients following limb preservation surgery. Methods. This observational study comprised 127 DF patients. All enrolled patients had undergone foot surgery and were off-loaded empirically as follows: wheelchair+removable contact splint (RCS) (group R: 29.2%), wheelchair only (group W: 48%), and wheelchair+removable prefabricated device (group WP: 22.8%). We compared the primary (e.g., the number of healed patients, healing time, and duration of antibiotic (ATB) therapy) and secondary outcomes (e.g., number of reamputations and number and duration of rehospitalizations) with regard to the operation regions across all study groups. Results. The lowest number of postoperative complications (number of reamputations: p=0.028; rehospitalizations: p=0.0085; and major amputations: p=0.02) was in group R compared to groups W and WP. There was a strong trend toward a higher percentage of healed patients (78.4% vs. 55.7% and 65.5%; p=0.068) over a shorter duration (13.7 vs. 16.5 and 20.3 weeks; p=0.055) in the R group, as well. Furthermore, our subanalysis revealed better primary outcomes in patients operated in the midfoot and better secondary outcomes in patients after forefoot surgery—odds ratios favouring the R group included healing at 2.5 (95% CI, 1.04-6.15; p=0.037), reamputations at 0.32 (95% CI, 0.12-0.84; p=0.018), and rehospitalizations at 0.22 (95% CI, 0.08-0.58; p=0.0013). Conclusions. This observational study suggests that removable contact splint combined with a wheelchair is better than a wheelchair with or without removable off-loading device for accelerating wound healing after surgical procedures; it also minimises overall postoperative complications, reducing the number of reamputations by up to 77% and the number of rehospitalizations by up to 66%.

Aims Our aim was to comprehensively estimate the incidence of diabetic foot ulcer (DFU) recurrence and corresponding risk factors in two cohorts. Methods Prospective data from patients with active DFU from two diabetes centres in Germany (GER, n = 222) and the Czech Republic (CZ, n = 99) were analysed. Crude cumulative incidences were obtained. Additionally, time to recurrence and risk factors were investigated using multivariate Cox models. Results 69%(154) of patients in GER and 70%(69) in CZ experienced at least one DFU recurrence; 25%(56) in DEU and 15%(15) in CZ died; 5%(11) and 9%(9) were lost to follow-up. The crude cumulative incidence in the first year was 28% in GER and 25% in CZ; 68%/70% within ten years, and 69%/70% in 15 years. In GER, renal replacement therapy was associated with shorter time to recurrence (HR = 3.71, 95%CI:1.26–10.87); no history of DFU before the index lesion with longer time to recurrence (HR = 0.62, 0.42–0.92). In CZ, type 2 diabetes (HR = 2.57, 1.18–5.62) and index ulcer treatment by minor amputation (HR = 2.11, 1.03–4.33) were associated with shorter time to recurrence. Conclusions Cumulative DFU recurrence was approximately 70% in 15 years in both cohorts. We found a significantly higher risk of future recurrence in patients having a consecutive ulcer compared with the first ever ulcer.

The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO2) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO2 at 1 month after ACT ( r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.

Perfusion scintigraphy with technetium-99-methoxy-isobutyl-isonitrile (99mTc-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 99mTc-MIBI was an eligible method for evaluation of the effect of cell therapy on critical limb ischemia (CLI) in diabetic patients. 99mTc-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 (TcPO2) that served as a reference method. The effect of ACT was confirmed by a significant increase in TcPO2 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 TcPO2 changes. Results of our study showed no significant contribution of 99mTc-MIBI of calf muscles to the assessment of ACT in diabetic patients with CLI over a 3-month follow-up period.

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.

The release of proangiogenic cytokines into the circulation after stem cell (SC) therapy and compensatory increase of angiogenesis inhibitors may reflect local vasculogenesis but also can increase the risk of side effects. The aim of our study was to evaluate serum levels of angiogenic cytokines with regard to the assessment of local and systemic vasculogenesis in diabetic patients with no-option critical limb ischemia (NO-CLI). Twenty-five diabetic patients with NO-CLI treated with SCs isolated from bone marrow or stimulated peripheral blood were included in the study. Serum levels of proangiogenic cytokines (VEGF, bFGF, Ang-1, PDGF-AA, and PDGF-BB) and an antiangiogenic cytokine (endostatin) were assessed 6 months after cell treatment, compared to baseline values, and correlated with the number of injected CD34+ cells. The clinical effect of SC therapy (assessed by changes in TcPO2) and potential systemic vasculogenesis (assessed by eye fundus examination) were evaluated after 6 months. Serum levels of angiogenic inhibitor endostatin increased significantly after 1 and 3 months ( p = 0.0003), but no significant increase in serum levels of proangiogenic cytokines was observed. A significant correlation between number of injected CD34+ cells and serum levels of endostatin was observed ( r = 0.41, p < 0.05); however, proangiogenic cytokines did not correlate with CD34+ cells. No correlation between increase in TcPO2 after treatment and serum levels of any of the angiogenic cytokines were seen, and no signs of systemic vasculogenesis in the retina were observed after 6 months. Despite the significant increase in the levels of the angiogenic inhibitor endostatin following SC treatment, there was no risk of systemic vasculogenesis after SC therapy as documented by serum levels of proangiogenic cytokines or changes in the retina.

One of the most serious complications of the diabetic foot (DF) is a major amputation, which is associated with poor patient prognosis. The occurrence of major amputations may be influenced by a variety of factors including deep infection caused by resistant pathogens.The aims of our study were to compare the incidence of major amputations in podiatric center, characteristics of amputated patients with the DF and other factors contributing to major amputations in last decade.We included into our study all patients hospitalized for the DF in our center whose underwent major amputations from 9/2004 to 9/2006 (group 1) and from 9/2013 to 9/2015 (group 2). Risk factors such as severity of DF ulcers based on Texas classification, duration of previous anti-biotic therapy, the presence and severity of peripheral arterial disease (PAD) according to Graziani classification, the number of revascularizations, renal failure/hemodialysis, osteomyelitis, infectious agents found before amputations and their resistance were compared between the study groups.During the 1st study period (9/2004-9/2006) 373 patients were hospitalized for the DF, of whom 3.2 % underwent major amputation (12/373 - group 1), during the 2nd study period (9/2013-9/2015) 376 patients, of whom 5.1 % absolved major amputation (19/376 - group 2). As the numbers of major amputations as their indications were similar in both study groups. The study groups did not differ significantly in the age, BMI, duration and type of diabetes, duration of DF and severity of DF ulcers, the presence of renal failure/hemodialysis, osteomyelitis and PAD. Group 2 had milder forms of PAD by Graziani classification (4.4 ±1.4 vs 5.7 ± 0.9; p = 0.012) and a higher number of revascularizations before major amputations (2.5 ± 1.5 vs 1 ± 1; p = 0.003) compared to the group 1. These patients were significantly longer treated by antibiotics (5.4 ± 2.4 vs 2.5 ± 2 months; p = 0.002) and underwent more resections and minor amputations (3.1 ± 2.1 vs 0.9 ± 0.5; p = 0.0004) before major amputations in contrast to the group 1. There was a trend to higher incidence of Gram-negatives (65.1 % vs 61.5 %; NS) with a predominance of Enterobacteriacae species (60.7 % vs 56 %; NS) and a trend to the increase of Pseudomonas (25 % vs 18.8 %; NS) and Enterococci sp. (46.7 % vs 20 %; NS) in the group 2 compared to the group 1. The incidences as of MRSA, multidrug resistant Pseudomonas sp. of other resistant microbes were similar in both study groups.The incidence of major amputations in patients hospitalized for the DF remains unchanged during the last decade. The therapy of factors leading to amputations has evidently intensified. This is in accordance with the latest international recommendations for the therapy of DF. In the future, it is appropriate to focus on the improvement of detection and treatment of infection and ischemia in such risk group of patients.Key words: diabetic foot - major amputation.

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.

Podiatry is the science dealing with the diagnostics and treatment of the foot and ankle and associated tissues and structures by all appropriate methods and also with the local manifestation of the overall processes in this area. Diabetic foot disease is defined as infection, ulceration or destruction of tissues of the foot associated with neuropathy and/or peripheral artery disease in the lower extremity of people with diabetes according to the latest edition of the International Consensus. Successful treatment and prevention of diabetic foot syndrome depends on a holistic approach, in which it is seen as part of the multiple organ involvement. Teamwork of series of experts is therefore necessary. Internist with diabetes and podiatric education plays a key role in this team in particular, when control diabetes and in the prevention and treatment of co-morbidities, in the diagnosis of malnutrition and in the nutritional therapy and in the early diagnosis and effective treatment of infections. Last but not least, internist in collaboration with other professionals works when treatment of lower limb ischemia, suitable offloading of the ulcer and topical therapy and in the prevention of ulcers. Recurrent ulcerations are the major problem in podiatry and it can occur in up to 40% of patients in the first year after healing. Follow-up of patients with diabetic foot syndrome by experienced internist can help reduce the serious consequences, including amputation and cardiovascular mortality.Key words: diabetic foot - internal medicine - podiatry.

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

Few studies have examined factors associated with diabetic foot ulcer (DFU) recurrence. Using data from patients enrolled in the prospective Eurodiale DFU study, we investigated the frequency of and risk factors for DFU recurrence after healing during a 3‐year follow‐up period. At our site, 93 Eurodiale‐enrolled patients had a healed DFU. Among these, 14 were not alive; of the remaining 79 patients we enrolled 73 in this study. On entry to the Eurodiale study, we assessed demographic factors (age, sex and distance from hospital); diabetes‐related factors [duration, and glycated haemoglobin (HbA1c) levels]; comorbidities (obesity, renal failure, smoking and alcohol abuse) and DFU‐related factors [peripheral arterial disease, ulcer infection, C‐reactive protein (CRP) and; foot deformities]. During the 3‐year follow‐up period, a DFU had recurred in 42 patients (57·5%). By stepwise logistic regression of findings at initial DFU presentation, the significant independent predictors for recurrence were plantar ulcer location [odds ratio (OR) 8·62, 95% confidence interval (CI) 2·2–33·2]; presence of osteomyelitis (OR 5·17, 95% CI 1·4–18·7); HbA1c > 7·5% ([DCCT], OR 4·07, 95% CI 1·1–15·6) and CRP > 5 mg/l (OR 4·27, 95% CI 1·2–15·7). In these patients with a healed DFU, the majority had a recurrence of DFU during a 3‐year follow‐up period, despite intensive foot care. The findings at diagnosis of the initial DFU were independent risk factors associated with ulcer recurrence (plantar location, bone infection, poor diabetes control and elevated CRP) and define those at high risk for recurrence, but may be amenable to targeted interventions.

The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity. (J Am Podiatr Med Assoc 101(5): 437–446, 2011)

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.

Charcot’s or neuropathic osteoarthropathy is one of the most debilitating orthopedic sequelae of diabetes mellitus. Distinguishing Charcot’s neuroarthropathy from clinically similar conditions may be challenging. The neurovascular theory postulates that Charcot’s neuroarthropathy may be secondary to sympathetic denervation of the lower-extremity vasculature. A convenient method for assessing autonomic neuropathy in patients with Charcot’s neuroarthropathy is needed. Short-term power spectral analysis (PSA) of heart rate variability (HRV), a noninvasive and quantitative method for assessing autonomic neuropathy, may be advantageous compared with the traditionally used Ewing’s cardiovascular reflex tests. However, there are limitations to the clinical use of PSA of HRV because of poor standardization. We standardized PSA of HRV and assessed autonomic neuropathy in 17 people with acute Charcot’s neuroarthropathy using PSA of HRV versus Ewing’s tests. More patients with Charcot’s neuroarthropathy were diagnosed as having autonomic neuropathy with PSA of HRV than with Ewing’s tests (94% versus 82%); however, no significant difference between the two methods was found. The results of this study suggest that PSA of HRV requires minimal patient collaboration and time expenditure compared with Ewing’s tests and may be useful in detecting autonomic neuropathy in patients with Charcot’s neuroarthropathy. (J Am Podiatr Med Assoc 96(1): 1–8, 2006)

Infectious complications of the diabetic foot may be influenced by impaired renal function and by immunosuppression therapy. Aims: To assess differences in microbial findings and resistance to antibiotics between transplant recipients, hemodialysis patients, and other patients with the diabetic foot. Methods: 207 patients treated in the foot clinic for diabetic ulcers from 12/1998 to 12/1999 were included into this retrospective study. Patients were divided into three groups (transplant, dialysis, and other patients). Occurrence of individual bacterial species and resistance to antibiotics was compared between study groups. Results: Study groups did not differ significantly in ulcer grades defined by the Wagner classification or in the mean number of pathogens per patient. The prevalence of individual microorganisms did not differ between the study groups. However, the study groups differed significantly in the occurrence of microbial resistance to antibiotics. Transplant patients had more frequently Staphylococcus aureus resistant to oxacillin (P

The aim of our case-control study was to compare selected psychological and social characteristics between diabetic patients with and without the DF (controls).104 patients with and 48 without DF were included into our study. Both study groups were compared in terms of selected psychosocial characteristics.Compared to controls, patients with DF had a significantly worse quality of life in the area of health and standard of living as shown by lower physical health domain (12.7 ± 2.8 versus 14.7 ± 2.5; P0.001) and environment domain (14.1 ± 2.2 versus 15 ± 1.8; P0.01) that negatively correlated with diabetes duration (r = -0.061; P = 0.003). Patients with DF subjectively felt more depressed in contrast to controls (24.5 versus 7.3%; P0.05); however, the depressive tuning was objectively proven in higher percentage in both study groups (83.2 versus 89.6; NS). We observed a significantly lower level of achieved education (P0.01), more patients with disability pensions (P0.01), and low self-support (P0.001) in patients with the DF compared to controls. In the subgroup of patients with a previous major amputation and DF (n = 6), there were significantly worse outcomes as in the environment domain (P0.01), employment status, and stress readaptation (P0.01) in contrast to the main study groups.Patients with DF had a predominantly worse standard of living. In contrast to our expectations, patients with DF appeared to have good stress tolerability and mental health (with the exception of patients with previous major amputation) and did not reveal severe forms of depression or any associated consequences.

Background aims. The aim of our study was to compare the effect of autologous stem cell therapy (SCT) and percutaneous transluminal angioplasty (PTA) on diabetic foot disease (DFD) in patients with critical limb ischemia (CLI). Methods. Thirty-one patients with DFD and CLI treated by autologous stem cells and 30 patients treated by PTA were included in the study; 23 patients with the same inclusion criteria who could not undergo PTA or SCT formed the control group. Amputation-free survival, transcutaneous oxygen pressure (TcPO2) and wound healing were assessed over 12 months. Results. Amputation-free survival after 6 and 12 months was significantly greater in the SCT and PTA groups compared with controls (P ¼ 0.001 and P ¼ 0.0029, respectively) without significant differences between the active treatment groups. Increase in TcPO2 did not differ between SCT and PTA groups until 12 months (both Ps < 0.05 compared with baseline), whereas TcPO2 in the control group did not change over the follow-up period. More healed ulcers were observed up to 12 months in the SCT group compared with the PTA and control groups (84 versus 57.7 versus 44.4 %; P ¼ 0.042). Conclusions. Our study showed comparable effects of SCT and PTA on CLI, a major amputation rate that was superior to conservative therapy in patients with diabetic foot and an observable effect of SCT on wound healing. Our results support SCT as a potential promising treatment in patients with CLI and diabetic foot.

The aim of our case-control study was to compare selected psychological and social characteristics between diabetic patients with and without the DF (controls).Methods. 104 patients with and 48 without DF were included into our study. Both study groups were compared in terms of selected psychosocial characteristics.Results. Compared to controls, patients with DF had a significantly worse quality of life in the area of health and standard of living as shown by lower physical health domain (12.7±2.8versus14.7±2.5;P<0.001) and environment domain (14.1±2.2versus15±1.8;P<0.01) that negatively correlated with diabetes duration (r=-0.061;P=0.003). Patients with DF subjectively felt more depressed in contrast to controls (24.5 versus 7.3%;P<0.05); however, the depressive tuning was objectively proven in higher percentage in both study groups (83.2 versus 89.6; NS). We observed a significantly lower level of achieved education (P<0.01), more patients with disability pensions (P<0.01), and low self-support (P<0.001) in patients with the DF compared to controls. In the subgroup of patients with a previous major amputation and DF (n=6), there were significantly worse outcomes as in the environment domain (P<0.01), employment status, and stress readaptation (P<0.01) in contrast to the main study groups.Conclusions. Patients with DF had a predominantly worse standard of living. In contrast to our expectations, patients with DF appeared to have good stress tolerability and mental health (with the exception of patients with previous major amputation) and did not reveal severe forms of depression or any associated consequences.

Aims To assess calcaneal ultrasonometry in Charcot osteoarthropathy (CO) and to compare it with densitometry measured by dual energy X-ray absorptiometry (DEXA) and with bone remodelling markers. Patients and methods A group of 16 diabetic patients in the acute stage of CO with a mean age (± sd) of 51 ± 13 years was compared with 26 sex- and age-matched control subjects. Both calcaneal quantitative ultrasound (QUS) parameter stiffness and bone mineral density (BMD) measured in lumbar spine and femoral neck by DEXA were compared. Collagen type I cross-linked C-telopeptides (ICTP) were used for assessment of bone resorption. Results Patients with acute CO had significantly lower stiffness of the calcaneus in the Charcot and non-Charcot foot (both P

The aim of the study was the comparison of a simple standardized noninvasive examination of neuropathy and angiopathy with routine diagnostic practice in community diabetes clinics for the identification of patients at risk of foot ulceration. Consecutive patients (n=322), aged 30 years and more, with a diabetes duration of more than 5 years, were examined by trained podiatric nurses in six diabetes clinics over a 1-year period; 44 of these patients had active or previous foot ulcerations. We evaluated the differences between the routine diagnostic practice (based on the patient's medical history and a physical examination) and noninvasive testing of peripheral neuropathy [vibration perception threshold (VPT) and the Semmes-Weinstein 10-g monofilament wire system] and angiopathy [Doppler ankle/brachial index (ABI)]. Using receiver operating characteristic (ROC) analysis, we evaluated the sensitivity and specificity of noninvasive testing methods for identifying patients at risk and selecting the optimal diagnostic cutoff points. Patients with severe neuropathy, as determined by noninvasive testing (VPT > or =30 V and/or insensitivity to 10 g monofilament), had been diagnosed to have neuropathy in diabetes clinics in 54% of cases. Patients with angiopathy at risk of developing diabetic foot ulcers (ABI < or =0.8) had been diagnosed, in diabetes clinics, to have peripheral arterial disease in 50% (they reported claudications in 41%, had femoral artery bruits detected in 29% and nonpalpable peripheral pulsations in 12%). Our findings stress the importance of using standardized simple noninvasive testing methods to increase the accuracy of identifying patients at risk for the diabetic foot at the community level.

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)

Charcot neuroosteoarthropathy (CNO) can lead to disruption of the bone architecture of the foot (1). Increased osteoclastic activity is believed to be responsible for the bone destruction in CNO (2). Previous studies showed COOH-terminal telopeptide region of type 1 collagen (1CTP) and bone-specific alkaline phosphatase (BALP) as useful markers of bone turnover in patients with CNO (3–5). Presently, only bisphosphonates have been demonstrated to have some benefit in patients with CNO (6). However, bisphosphonates may have potential disadvantages in that they decrease bone remodeling and are contraindicated in patients with renal insufficiency (7). Our previous study (8) showed positive effects of calcitonin on bone resorption in patients with acute CNO. In this study, we set out to assess the effect of calcitonin on bone metabolism and disease activity during a 6-month treatment with intranasal calcitonin in acute CNO. Thirty-two consecutive patients with acute CNO were entered into the study. Subjects were recruited from our diabetic foot clinic during a 17-month period and were followed up for 6 months. The study was approved by the local ethics committee, and all participants gave written informed consent. Acute CNO was defined by clinical signs: warm, swollen foot and skin temperatures ≥2°C at the site of maximum deformity of the affected foot compared with a similar site on the contralateral foot (infrared thermometer) and confirmed by plain X-ray and three-phase technetium bone scan (9). The presence of diabetic neuropathy was determined by measurement of vibration perception …

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.