Endothelial Dysfunction in Diabetes Mellitus: New Insights.

Endothelial dysfunction (ED) is an important marker of future atherosclerosis and cardiovascular disease, especially in people with diabetes. This article summarizes the evidence on endothelial dysfunction in people with diabetes and adds different perspectives that can affect the presence and severity of ED and its consequences. We highlight that data on ED in type 1 diabetes are lacking and discuss the relationship between ED and arterial stiffness. Several interesting studies have been published showing that ED modulates microRNA, microvesicles, lipid levels, and the endoplasmatic reticulum. A better understanding of ED could provide important insights into the microvascular complications of diabetes, their treatment, and even their prevention.

Monitoring of amoxicilline and ceftazidime in the microdialysate of diabetic foot and serum by capillary electrophoresis with contactless conductivity detection.

Determination of the broad-spectrum antibiotics amoxicilline (AMX) and ceftazidime (CTZ) in blood serum and microdialysates of the subcutaneous tissue of the lower limbs is performed using CE with contactless conductivity detection (C4 D). Baseline separation of AMX is achieved in 0.5 M acetic acid as the background electrolyte and separation of CTZ in 3.2 M acetic acid with addition of 13% v/v methanol. The CE-C4 D determination is performed in a 25 µm capillary with suppression of the EOF using INST-coating on an effective length of 18 cm and the attained migration time is 4.2 min for AMX and 4.4 min for CTZ. The analysis was performed using 20 µl of serum and 15 µl of microdialysate, treated by the addition of acetonitrile in a ratio of 1/3 v/v and the sample is injected into the capillary using the large volume sample stacking technique. The LOQ attained in the microdialysate is 148 ng/ml for AMX and 339 ng/ml for CTZ, and in serum 143 ng/ml for AMX and 318 ng/ml for CTZ. The CE-C4 D method is employed for monitoring the passage of AMX and CTZ from the blood circulatory system into the subcutaneous tissue at the sites of diabetic ulceration in patients suffering from diabetic foot syndrome and also for measuring the pharmacokinetics following intravenous application of bolus antibiotic doses.

Detection, examination and therapy of sexual dysfunctions in patients with diabetes.

Diabetes mellitus is a disease associated with multiple complications due to ineffective diabetes management in the early period after diagnosis and especially in the long term. However, the risk of developing sexual dysfunctions, which affect both men and women, is rarely mentioned in association with diabetes (1). Sexual complications not only disrupt with the social and sexual life of patients, but are often the first symptom of other health problems. For these reasons, in people with diabetes, early detection and proper treatment of sexual dysfunctions should be of concern physicians caring for diabetic patients.

Podiatric care from diabetologists point of view.

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. METHODS: To find out the study data, we prepared in cooperation with the ČDS ČLS JEP Committee a questionnaire survey for outpatient diabetology specialists. RESULTS: 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. CONCLUSION: 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.

What are the specifics of diabetic foot syndrome and why we need interdisciplinary recommendations for its diagnosis and treatment?

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.

Diabetic foot.

Diabetic foot (DF) is a serious late complication of diabetes associated with high morbidity and mortality, often leading to lower limb amputation. Risk factors for DF include neuropathy, infection, and ischemia. The prevention of ulceration is essential for reducing amputation rate. Effective follow-up of patients and application of preventive approaches such as using of appropriate shoes and foot care can reduce the incidence of ulcerations by up to 50 %. DF treatment is very expensive and includes offloading of the affected foot, treatment of infection and revascularization. Local treatment and satisfactory diabetes control are also very important. Professional care for these patients should be directed to specialized podiatric clinics due to the need for a multidisciplinary approach.

[Diabetic foot syndrome: importance of calf muscles MR spectroscopy in the assessment of limb ischemia and effect of revascularization]. / Syndrom diabetické nohy: význam MR spektroskopie lýtkových svalu pro hodnocení koncetinové ischemie a efektu revaskularizace.

AIM: 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. METHODS: 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. RESULTS: Patients with CLI had significantly lower PCr/Pi (p < 0.001), significantly higher Pi and pH (both p < 0.01), significantly lower Qmax and prolonged τPCr (both p < 0.001) 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, p < 0.005). 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. CONCLUSION: 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.

[Has been changed numbers and characteristics of patients with major amputations indicated for the diabetic foot in our department during last decade?] / Doslo v posledním desetiletí ke zmene poctu a charakteristik pacientu se syndromem diabetické nohy hospitalizovaných k vysoké amputaci na specializovaném podiatrickém pracovisti?

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparison of the effect of stem cell therapy and percutaneous transluminal angioplasty on diabetic foot disease in patients with critical limb ischemia.

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 = 0.001 and P = 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 = 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.

Gut microbiota in relationship to diabetes mellitus and its late complications with a focus on diabetic foot syndrome: A review.

Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.

Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? Results of the DFIATIM substudy.

Aims/hypothesis: The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. Methods: For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). Results: Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 µgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 µgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 µgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 µgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). Conclusions: Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.

Risk factors for recurrence of diabetic foot ulcers: prospective follow-up analysis in the Eurodiale subgroup.

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 Effects of Immunosuppressive Drugs on the Characteristics and Functional Properties of Bone Marrow-Derived Stem Cells Isolated from Patients with Diabetes Mellitus and Peripheral Arterial Disease.

BACKGROUND: Diabetic patients (DPs) with foot ulcers can receive autologous cell therapy (ACT) as a last therapeutic option. Even DPs who have undergone organ transplantation and are using immunosuppressive (IS) drugs can be treated by ACT. The aim of our study was to analyze the effects of IS drugs on the characteristics of bone marrow-derived stem cells (BM-MSCs). METHODS: The cells were isolated from the bone marrow of DPs, cultivated for 14-18 days, and phenotypically characterized using flow cytometry. These precursor cells were cultured in the presence of various IS drugs. The impact of IS drugs on metabolic activity was measured using a WST-1 assay, and the expression of genes for immunoregulatory molecules was detected through RT-PCR. Cell death was analyzed through the use of flow cytometry, and the production of cytokines was determined by ELISA. RESULTS: The mononuclear fraction of cultured cells contained mesenchymal stem cells (CD45-CD73+CD90+CD105+), myeloid angiogenic cells (CD45+CD146-), and endothelial colony-forming cells (CD45-CD146+). IS drugs inhibited metabolic activity, the expression of genes for immunoregulatory molecules, the production of cytokines, and the viability of the cells. CONCLUSIONS: The results indicate that IS drugs in a dose-dependent manner had a negative impact on the properties of BM-MSCs used to treat ischemic diabetic foot ulcers, and that these drugs could affect the therapeutic potential of BM-MSCs.

Cell Therapy of Severe Ischemia in People with Diabetic Foot Ulcers-Do We Have Enough Evidence?

This current opinion article critically evaluates the efficacy of autologous cell therapy (ACT) for chronic limb-threatening ischemia (CLTI), especially in people with diabetes who are not candidates for standard revascularization. This treatment approach has been used in 'no-option' CLTI in the last two decades and more than 1700 patients have received ACT worldwide. Here we analyze the level of published evidence of ACT as well as our experience with this treatment method. Many studies have shown that ACT is safe and an effective method for patients with the most severe lower limb ischemia. However, some trials did not show any benefit of ACT, and there is some heterogeneity in the types of injected cells, route of administration and assessed endpoints. Nevertheless, we believe that ACT plays an important role in a comprehensive treatment of patients with diabetic foot and severe ischemia.

Microdialysis as a tool for antibiotic assessment in patients with diabetic foot: a review.

Diabetic foot is a serious late complication frequently caused by infection and ischaemia. Both require prompt and aggressive treatment to avoid lower limb amputation. The effectiveness of peripheral arterial disease therapy can be easily verified using triplex ultrasound, ankle-brachial/toe-brachial index examination, or transcutaneous oxygen pressure. However, the success of infection treatment is difficult to establish in patients with diabetic foot. Intravenous systemic antibiotics are recommended for the treatment of infectious complications in patients with moderate or serious stages of infection. Antibiotic therapy should be initiated promptly and aggressively to achieve sufficient serum and peripheral antibiotic concentrations. Antibiotic serum levels are easily evaluated by pharmacokinetic assessment. However, antibiotic concentrations in peripheral tissues, especially in diabetic foot, are not routinely detectable. This review describes microdialysis techniques that have shown promise in determining antibiotic levels in the surroundings of diabetic foot lesions.

Pain Management in Older Adults with Chronic Wounds.

Older people often suffer from different types of ulcers, with the most prevalent being chronic leg ulcers (CLUs) and diabetic foot ulcers. There are major issues in the current medical approach because these ulcers are hard to heal, and, in the case of CLUs, very painful and with a high frequency of relapse. Older people complain of pain more frequently than young people, frequently due to a combination of painful chronic wounds with other comorbidities (e.g. arthritis, peripheral arterial disease, vertebrogenic pain syndrome). However, chronic pain appears to be managed better by older people because the pain sensitivity is downregulated and the pain threshold is higher in older people. Pain management of chronic wounds is often insufficient, especially in older individuals. It is highly important to use non-traumatic wound dressings and pay attention to patients' feelings and fears because pain in chronic ulcers can impair wound healing. Key factors include good preparation for dressing change and adequate analgesia, ideally a combination of topical and oral agents.

Comparison of Three Methods for Preparation of Autologous Cells for Use in Cell Therapy of Chronic Limb-Threatening Ischemia in People with Diabetes.

Autologous cell therapy (ACT) is a new therapeutic approach for diabetic patients with no-option chronic limb-threatening ischemia (NO-CLTI). The aim of our study was to quantify cell populations of cell therapy products (CTPs) obtained by three different isolation methods and to correlate their numbers with changes in transcutaneous oxygen pressure (TcPO2). CTPs were separated either from stimulated peripheral blood (PB) (n = 11) or harvested from bone marrow (BM) processed either by Harvest SmartPReP2 (n = 50) or sedimented with succinate gelatin (n = 29). The clinical effect was evaluated by the change in TcPO2 after 1, 3 and 6 months. TcPO2 increased significantly in all three methods at each time point in comparison with baseline values (p < .01) with no significant difference among them. There was no correlation between the change in TcPO2 and the size of injected cell populations. We only observed a weak correlation between the number of injected white blood cells (WBC) and an increase in TcPO2 at 1 and 3 months. Our study showed that all three isolation methods of ACT were similarly relatively efficient in the treatment of NO-CLTI. We observed no correlation of TcPO2 increase with the number of injected monocytes, lymphocytes or CD34+. We observed a weak correlation between TcPO2 increase and the number of injected WBCs.

Effects of a 12-Week Interventional Exercise Programme on Muscle Strength, Mobility and Fitness in Patients With Diabetic Foot in Remission: Results From BIONEDIAN Randomised Controlled Trial.

Objectives: Diabetic foot syndrome (DFS) is a serious late diabetic complication characterised by limited joint mobility and other biomechanical and muscle abnormalities. Aim: To evaluate the effect of an interventional exercise programme on anthropometric parameters, muscle strength, mobility and fitness in patients with diabetic foot in remission. Data Sources and Study Selection: Thirty-eight patients with type 2 diabetes and DFS without active lesions (mean age 65 ± 6.9 years, BMI 32 ± 4.7 kg.m-2, waist-hip ratio (WHR)1.02 ± 0.06) were enrolled in our randomised controlled trial. All subjects were randomised into two groups: an intervention group (I; n=19) and a control group (C; n=19). The 12-week exercise intervention focused on ankle and small-joint mobility in the foot, strengthening and stretching of the lower extremity muscles, and improvements in fitness. Changes (Δ=final minus initial results) in physical activity were assessed using the International Physical Activity Questionnaire (IPAQ), with joint mobility detected by goniometry, muscle strength by dynamometry, and fitness using the Senior Fitness Test (SFT). Data extraction: Due to reulceration, 15.8% of patients from group I (3/19) and 15.8% of patients from group C were excluded. Based on the IPAQ, group I was more active when it came to heavy (p=0.03) and moderate physical activity (p=0.06) after intervention compared to group C. Group I improved significantly in larger-joint flexibility (p=0.012) compared to controls. In group I, dynamometric parameters increased significantly in both lower limbs (left leg; p=0.013, right leg; p=0.043) compared to group C. We observed a positive trend in the improvement of fitness in group I compared to group C. We also confirmed positive correlations between heavy physical activity and selected parameters of flexibility (r=0.47; p=0.007), SFT (r=0.453; p=0.011) and dynamometry (r=0.58; p<0.0025). Anthropometric parameters, such as BMI and WHR, were not significantly influenced by the intervention programme. Conclusion: Our 12-week interventional exercise programme proved relatively safe, resulting in improved body flexibility and increased muscle strength in DF patients in remission.

Comparison of the impact of autologous cell therapy and conservative standard treatment on tissue oxygen supply and course of the diabetic foot in patients with chronic limb-threatening ischemia: A randomized controlled trial.

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 NO-CLTI in comparison with standard treatment (ST) in a randomized controlled trial. Methods: Diabetic patients with NO-CLTI were randomized to receive either ACT (n=21) or ST (n=19). After 12 weeks, those in the ST group, who did not improve were treated with ACT. The effect of ACT on ischemia and wound healing was assessed by changes in transcutaneous oxygen pressure (TcPO2) and the number of healed patients at 12 weeks. Pain was evaluated by Visual Analogue Scale (VAS). Amputation rates and amputation-free survival (AFS) were assessed in both groups. Results: During the first 12 weeks, TcPO2 increased in the ACT group from 20.8 ± 9.6 to 41.9 ± 18.3 mm Hg (p=0.005) whereas there was no change in the ST group (from 21.2 ± 11.4 to 23.9 ± 13.5 mm Hg). Difference in TcPO2 in the ACT group compared to ST group was 21.1 mm Hg (p=0.034) after 12 weeks. In the period from week 12 to week 24, when ST group received ACT, the TcPO2 in this group increased from 20.1 ± 13.9 to 41.9 ± 14.8 (p=0.005) while it did not change significantly in the ACT in this period. At 24 weeks, there was no significant difference in mean TcPO2 between the two groups. Wound healing was greater at 12 weeks in the ACT group compared to the ST group (5/16 vs. 0/13, p=0.048). Pain measured using VAS was reduced in the ACT group after 12 weeks compared to the baseline, and the difference in scores was again significant (p<0.001), but not in the ST group. There was no difference in rates of major amputation and AFS between ACT and ST groups at 12 weeks. Conclusions: This study has showed that ACT treatment in patients with no-option CLTI and diabetic foot significantly improved limb ischemia and wound healing after 12 weeks compared to conservative standard therapy. Larger randomized controlled trials are needed to study the benefits of ACT in patients with NO-CLTI and diabetic foot disease. Trial registration: The trial was registered in the National Board of Health (EudraCT 2016-001397-15).

Verrucous Skin Lesions on the Feet in Diabetic Neuropathy in the Context of Podiatric Practice - Our Pilot Experiences.

Skin changes in patients with diabetic foot (DF) are relatively common. The most frequent lesions feature papillae or cilia of various forms. The condition known as "verrucous skin lesions on the feet in diabetic neuropathy" (VSLDN) occurs in patients with distal diabetic sensorimotor neuropathy and is commonly located in places of high mechanical pressure. However, there is a scarcity of published data on the diagnosis and treatment of VSLDN. Our paper describes various types of VSLDN skin pathology, summarizes the diagnostic procedure options available, and documents the experience of our diabetic foot clinic in applying short-term VSLDN therapies as part of routine podiatric practice.