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Diabetes mellitus (DM) is a non-communicable epidemic. The number of people with this pathology is growing every year. DM leads to a decrease in quality and life expectancy due to vascular complications. However, the manifestations of diabetes are varied, including possible skin manifestations, which often receive insufficient attention. This article analyzes and summarizes current knowledge about dermatological complications in patients with DM, with an emphasis on the pathogenetic mechanisms underlying these problems. This article focuses on xerosis, intertrigo and disorders of the skin's protective mechanisms during the development of diabetic foot. The article is aimed at developing practical recommendations for endocrinologists on skin care in patients with diabetes, in order to improve their quality of life and prevent complications. The need to expand patient education on skin care in Diabetes Schools is also discussed.

Purpose: Diabetic foot ulcer (DFU) is one of the most severe complications of type 2 diabetes, which is manifested in chronic skin ulcers of lower extremities. DFU treatment remains complex and expensive despite the availability of well-established protocols. Early prediction of potential DFU development at the onset of type 2 diabetes can greatly improve the aftermath of this complication. Methods: To assess potential genetic markers for DFU, a group of diabetic patients from Moscow region with and without DFU was genotyped for a number of SNPs previously reported to be associated with the DFU. Results: Obtained results did not confirm previously claimed association of rs1024611, rs3918242, rs2073618, rs1800629, rs4986790, rs179998, rs1963645 and rs11549465 (respectively, in MCP1, MMP9, TNFRSF11B, TNFα, TLR4, eNOS, NOS1AP and HIF1α genes) with the DFU. Surprisingly, the t allele of rs7903146 in the TCF7l2 gene known as one of the most prominent risk factors for type 2 diabetes has shown a protective effect on DFU with OR(95%) = 0.68(0.48–0.96). Conclusion: Non-replication of previously published SNP associations with DFU suggests that the role of genetic factors in the DFU onset is either highly variable in different populations or is not as significant as the role of non-genetic factors. [ABSTRACT FROM AUTHOR]

Aim: To compare the effectiveness of preventive interventions in reducing reccurrent diabetic foot ulcers. Meta-analysis (MA) was conducted to address clinical questions on this topic of the Italian guidelines on diabetic foot. Methods: This MA includes randomized controlled trials evaluating the effectiveness of various preventive interventions, namely: treatment of pre-ulcerative foot lesions, structured educational programs, psychological interventions and the use of therapeutic footwear to relieve plantar pressure in people with diabetes mellitus and a history of previous ulcers. Results: A total of 731 studies were identified and 14 were considered eligible for the analysis. We found that treatments of pre-ulcerative foot lesions did not provide any statistically significant effects (MH-OR: 0.84 [0.31, 2.33], p = 0.74, I2 = 38%). Conversely, structured educational programs were associated with a trend toward reduction of ulcer recurrence risk (MH-OR: 0.13 [0.01, 1.64], p = 0.10, I2 = 88%). No randomized controlled studies assessing the efficacy of psychological interventions have been retrieved. The use of therapeutic footwears can effectively reduce the risk of reulceration in diabetic patients with an history of previous DFU, in particular prefabricated rigid-soled therapeutic footwears showed a significant reduction of the risk of ulcer recurrence in comparison with semirigid soles (MH-OR: 0.17 [0.05, 0.57], p = 0.004). Conclusions: The study provides low-certainty evidence that, among preventive strategies in patients with previous DFU, rigid-sole therapeutic footwear and structured education programs are capable of reducing the risk of foot re-ulceration. [ABSTRACT FROM AUTHOR]

Diabetic foot syndrome is a syndrome of specific conditions affecting the foot. It is a complication of diabetes. It occurs in 12–25% of patients with diabetes. Untreated, it leads to irreversible deformities and necrosis of the foot, often resulting in amputation. In this study the statistics and consequences of diabetic foot syndrome are described. Patients with diabetes need to take care of their lower limbs. Proper footwear can prevent foot wounds. Available solutions for the prevention and treatment of diabetic foot syndrome are presented herein: footwear, insoles and requirements for footwear materials. Appropriate equipment for a person with diabetes, especially one who has been diagnosed with diabetic foot syndrome or is at risk of such a condition, includes footwear and replaceable insoles. The parameters of footwear, insoles and footwear materials that are most optimal for patients with diabetes and diabetic foot syndrome were defined. The effect of a pulsed electromagnetic field and pulsed ultrasound on diabetic foot problems was evaluated. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a rapidly growing health challenge and potential epidemic across low-and-middle-income countries like India. Diabetic retinopathy (DR) is a consequence of diabetic microangiopathy, which may cause visual deterioration due to macular edema in any stage and vitreous hemorrhage or tractional retinal detachment in the advanced proliferative retinopathy stages. Aims and Objectives: The aim was to study the retinopathy status in diabetic patients with a risk of diabetic foot syndrome (DFS) visiting a western regional hospital in India. Materials and Methods: In this cross-sectional study, all patients with diabetes mellitus (DM) with a risk of DFS, visiting a tertiary care hospital during the study period, underwent an ophthalmological evaluation for documentation of their retinopathy status. Results: One hundred and fourteen patients diagnosed to have a risk profile for DFS were included in the study. Their mean age was 61.22 years and 81.6% were males. The mean duration of DM was 12.24 years, respectively. Of the 114 patients, 72 had DR. An increased presence of retinopathy in patients with an increased risk grade of diabetic foot (DF) was found significant by the Chi‐square test. (P

Widespread introduction of ultrasound-guided regional anesthesia has increased the frequency of nerve blocks and the list of available nerves for blocking, particularly on the foot. In the area of the tibiocalcaneal joint, swellings of various etiologies are often found, including in patients with diabetes, who are characterized by high comorbidity. To date, the influence of edema on the effectiveness of local anesthetics is insufficiently studied. To evaluate the ultrasound criteria, we have analyzed and characterized the ultrasound pattern of 110 patients. When performing a nerve block in the area of the tibiocalcaneal joint, the time of the block onset and duration of sensory block in patients who underwent surgery for the diabetic foot depended reliably on the degree of ultrasound-diagnosed edema in the area of the block. The ultrasound method makes it possible to assess the degree of swelling in the area of blockade directly during conduction anesthesia. Further studies are needed to determine the root cause of this phenomenon, which may depend on the pH of the edema fluid or on dilution in the edema volume.

Background: Diabetes is a rapidly growing health challenge and potential epidemic across low-and-middle-income countries like India. Diabetic retinopathy (DR) is a consequence of diabetic microangiopathy, which may cause visual deterioration due to macular edema in any stage and vitreous hemorrhage or tractional retinal detachment in the advanced proliferative retinopathy stages. Aims and Objectives: The aim was to study the retinopathy status in diabetic patients with a risk of diabetic foot syndrome (DFS) visiting a western regional hospital in India. Materials and Methods: In this cross-sectional study, all patients with diabetes mellitus (DM) with a risk of DFS, visiting a tertiary care hospital during the study period, underwent an ophthalmological evaluation for documentation of their retinopathy status. Results: One hundred and fourteen patients diagnosed to have a risk profile for DFS were included in the study. Their mean age was 61.22 years and 81.6% were males. The mean duration of DM was 12.24 years, respectively. Of the 114 patients, 72 had DR. An increased presence of retinopathy in patients with an increased risk grade of diabetic foot (DF) was found significant by the Chi-square test. (P<0.001). Conclusion: Our study found an increased presence of DR in Western Indian cohort with DFS. The severity of retinopathy was greater in patients with higher grades of risk for DF, therefore establishment of an association between DR and DFS will help in developing an integrated management strategy for these two grave consequences of diabetes. [ABSTRACT FROM AUTHOR]

This article is a meta-analysis of randomized clinical trials on the use of prostanoids in patients with diabetes and chronic limb-threatening ischemia (CLTI) for the treatment of diabetic foot syndrome (DFS). The study found that prostanoids, such as iloprost and alprostadil, did not have a significant beneficial effect on major amputation, minor amputation, all-cause mortality, ulcer healing, pain, transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), quality of life, or peri-procedural complications. The authors concluded that the current evidence is not sufficient to support the extensive use of prostanoids in diabetic patients with CLTI, and further research is needed to determine their risk/benefit and cost/efficacy ratios. [Extracted from the article]

Regional methods of anesthesia are widely used in surgical interventions on the lower limb, in particular on the foot. But to date, the risks associated with performing distal blocks in patients with diabetes are insufficiently studied. We analyzed the 30-day consequences of tibiocalcaneal nerve block in 88 patients who underwent surgery for diabetic foot syndrome. The obtained results indicate the absence of an increased risk of infectious and trophic complications in the block area in the group of patients who underwent tibiocalcaneal nerve block compared to those with popliteal nerve block and the group of spinal anesthesia. The frequency of repeated operations was not significantly different in all 3 groups.

Relevance The number of amputations performed on patients with diabetic foot syndrome is increasing all over the world. Almost half of these operations are the so-called “minor amputations” carried out within the foot. The high recurrence rate of neuropathic ulcers, impaired biomechanics, and a decrease in the quality of life of patients after these surgeries encourage the study of this problem and the search for possible treatment options due to the capabilities of surgical treatment for post-amputation foot deformities.Aim of study To evaluate the nature of surgical interventions for post-amputation foot deformities in patients with diabetic neuropathy.Material and methods The literature search was carried out in the databases of medical publications PubMed, CyberLeninka, Google Scholar, Scopus, Medline, eLIBRARY among articles in English and Russian. The search was performed using the following terms: transmetatarsal resection, diabetic foot syndrome, transmetatarsal amputation, minor amputation.Results Surgical treatment methods for deformities after amputation of part of the forefoot are widely presented in the world literature and are more studied. The possibilities of correcting foot deformities that occurred after amputation of the entire anterior section (from transmetatarsal amputation to the level of the Chopart`s joint) are less covered, this direction and methods have been studied to a lesser extent.Conclusions Surgical methods for the correction of post-amputation foot deformities have firmly entered the wide international practice. Their effectiveness is confirmed by studies with a high level of evidence. Nevertheless, a wider, academic research of the problem of orthopedic status in patients with this pathology and the corresponding methods of surgical treatment is required.

Background: In vascular medicine, peripheral arterial disease (PAD) and diabetic foot syndrome (DFS) are often considered synonymous with respect to the need for revascularization. In PAD patients, clinical symptoms reflect the degree of atherosclerotic disease, since peripheral innervation, including pain sensation, is not usually compromised. In DFS patients, however, symptoms of relevant foot ischemia are often absent and progression of ischemia goes unnoticed owing to diabetic polyneuropathy, the loss of nociception being the main trigger for foot ulcers. This review analyzes the fundamental differences between PAD and DFS against the background of polyneuropathy. Methods: The literature research for the 2014 revision of the German evidence-based S3-PAD-guidelines was extended to 2023. Results: Vascular examination is imperative for both, PAD and DFS. Stage-dependent revascularization is of utmost importance in PAD patients, especially those suffering from critical limb-threatening ischemia (CLTI). Successful therapy of DFS goes further, including infection and metabolic control, wound management, offloading the foot and lifelong prophylaxis in the course of a multidisciplinary treatment concept. Revascularization is not needed in all cases of DFS. Conclusions: There are fundamental differences between PAD and DFS with respect to pathophysiology, the anatomical distribution of arterial occlusive processes, the clinical symptoms, the value of diagnostic tools such as the ankle-brachial index, and classification. Also, therapeutic concepts differ substantially between the two patient populations. [ABSTRACT FROM AUTHOR]

Background. Treatment of chronic wounds in patients suffering from diabetic foot syndrome is one of the serious problems of practical surgery. Despite the constant improvement of methods aimed at improving the results of treatment of purulent-necrotic complications in these patients and preventing their occurrence in general, their frequency remains at the same level. An important factor influencing the slowdown of reparative processes in patients with diabetes mellitus is the presence of oxidative stress in the cells of the wound defect area. In conditions of diabetic angiopathy, the effectiveness of systemic pharmacotherapy is due to the impossibility of adequate delivery of drugs directly to the purulent-necrotic focus, which leads to the search for new methods of local treatment. Materials and methods. The results of treatment of 20 patients suffering from the neuroischemic form of diabetic foot syndrome with long-term non-healing wounds of the foot and lower leg were analyzed. In addition to standard therapy, the patients of the main group underwent the application of collagen gel from a matrix impregnated with antioxidants. Patients in the comparison group were treated only with standard therapy. The rate of reduction of the wound surface area and the activity of the microcirculatory bed in the area of the wound defect were evaluated. Results and conclusions. In patients of the main groups, shorter wound healing times were noted than in patients of the comparison group, as well as improved tissue microcirculation against the background of restoring balance in the lipid peroxidation system.

Background: Diabetes mellitus (DM) is associated with a higher prevalence of many forms of cancer. Diabetic foot syndrome (DFS) is associated with higher risk of lower limb amputation and mortality not all explainable with a cardiovascular profile at greater risk compared with DM patients without DFS. DFS could be associated with an increasing cancer incidence. To explore a possible link between DFS and cancer, comparing two cohorts of patients (DFS+ and DFS−) with a cohort of superimposable non-DM controls. Methods: We retrospectively analysed the databases of our department for all consecutive patients admitted between January 2019 and December 2021, selecting all DM pts, and sorting DFS+ pts, admitted for foot complications, from DFS− ones, admitted for other reasons. Cases of pancreatic cancer as well as cancer-related admissions were excluded. Patients were compared to non-DM patients admitted for non-oncological medical problems. The primary endpoint was to compare the prevalence of cancer among the groups, while the secondary endpoint was to look for predictors for cancer in the groups studied. Results: A cohort of 445 consecutive DM inpatients (222 DFS+ and 223 DFS−) and 255 controls were studied. Cancer prevalence in DFS+ group was significantly higher than in DFS− (p = 0.008) and controls (p = 0.031), while no differences were observed between DFS− and the controls. Univariate regression analysis showed a significant association between cancer and DFS (p = 0.007), age at admission (p ≤ 0.001), years of diabetes (p = 0.017) and haemoglobin concentration [Hb] (p = 0.030). In the multivariate regression analysis with DFS, age at admission and [Hb], only DFS (p = 0.021) and age at admission (p ≤ 0.001) persisted as independent factors associated with cancer. Conclusions: A higher prevalence of cancer in DFS+ patients than in DFS− patients and non-diabetic controls is reported. DFS and age can both be considered independent predictors of cancer in patients with DM. [ABSTRACT FROM AUTHOR]

Diabetes is a chronic disease associated with numerous complications including diabetic foot disorders, which are associated with significant morbidity and mortality as well as high costs. The costs associated with diabetic foot disorders comprise those linked to care (direct) and loss of productivity and poor quality of life (indirect). Due to the constant increase in diabetes prevalence, it is expected that diabetic foot disorder will require more resources, both in terms of caregivers and economically. We reviewed findings on management, morbidity, mortality, and costs related to diabetic foot disorder. [ABSTRACT FROM AUTHOR]

BACKGROUND. Growth factors play a leading role in wound healing. Their deficiency in diabetic foot syndrome has been demonstrated in experimental studies, most of them performed on acute wounds. At the same time, currently the effectiveness of local therapy with growth factors of this category of patients, as well as indications and contraindications to it are contradictory and are a subject for discussion. There is no data on the content of growth factors in diabetic foot ulcers of various durations. Meanwhile, the results obtained will help to expand the understanding of the pathogenetic mechanisms of the course and outcomes of diabetic foot ulcers at different stages of healing.AIM: To evaluate the level of growth factors and their receptors in non-healing neuropathic diabetic foot ulcers of different duration.MATERIALS AND METHODS. 89 samples of neuropathic diabetic foot ulcers were examined. Immunohistochemical analysis of biopsies was performed using antibodies to the following growth factors and their receptors: vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), epidermal growth factor (EGF). Depending on the duration of the wound, the biopsies were divided into 3 groups: group 1 — ≤ 90 days, group 2 — 91-365 days, group 3 — > 365 days.RESULTS. In the samples of wounds, the duration of which did not exceed 90 days, the expression of growth factors and receptors to them was significantly higher than in wounds of longer duration (p=0.0001). There was no significant difference in quantitative indicators of the expression of growth factors and their receptors between wounds lasting from 91 to 365 days and more than 365 days. According to the data of correlation analysis, the expression of VEGF, IGF, EGF and their receptors has a significant negative dependence on the duration of the wound (p= 0.0001).CONCLUSION. In diabetic foot ulcers lasting less than 90 days, the expression of growth factors such as VEGF, IGF, EGF and their receptors is significantly higher than in wounds of longer duration. The dependence of the expression of growth factors on the duration of the ulcer was revealed. The data obtained may explain the differences in the outcomes of chronic wounds and the absence in some cases of the effect of local therapy with growth factors.

The results of treatment of 123 patients with diabetic foot syndrome were analyzed. According to modern concepts, the leading cause of the development of diabetic foot syndrome and subsequent amputation is diabetic polyneuropathy of the lower extremities. The latter and associated foot deformities, as well as the loss of protective pain sensitivity, lead to spontaneous ulcerative defects in the soft tissues of the foot with their further infection and the development of a purulent-necrotic process. Their dermographic data, anamnesis, clinical manifestations and the course of the disease, the state of compensation of carbohydrate and lipid metabolism were studied. The severity of neuropathy, its clinical manifestations, the presence of ulcerative-necrotic lesions, their origin, the presence of concomitant macroangiopathy of the lower extremities, the condition of the bones of the foot, the presence of manifestations of microangiopathy were determined. A study was also conducted on the effectiveness and tolerability of patients with different doses of alpha-lipoic acid preparations (600, 900 and 1200 mg per day), which was used for the etiotropic treatment of neuropathy. The effect of alpha-lipoic acid on the treatment of diabetic neuropathy in patients suffering from purulent-necrotic forms of diabetic foot syndrome was studied. The high efficiency of the use of this group of drugs, both in standard and in increased doses, has been established. The study demonstrated that parenteral administration of alpha-lipoic acid preparations, both at a dose of 600 mg, and 900 and 1200 mg per day, is equally well tolerated by patients, does not cause significantly significant side effects and allows us to recommend the use of this group of drugs intravenously, followed by the use of 600 mg /day orally in the treatment of patients with diabetic foot syndrome complicated by ulcerative necrotic process.

Background. The issue of prevention and treatment of purulent-necrotic complications of diabetic foot syndrome is very relevant now. Despite the constant improvement of methods aimed at improving the results of treatment of purulent-necrotic complications in these patients and preventing their occurrence in general, their frequency remains at the same level. One of the factors affecting the wound process in patients with diabetes mellitus is the presence of oxidative stress in the area of the wound defect and in the perifocal zone. In conditions of diabetic angiopathy, the effectiveness of systemic pharmacotherapy is due to the impossibility of adequate delivery of drugs directly to the purulent-necrotic focus, which leads to the search for new methods of local treatment. Materials and methods. An experimental study of the effect of extracellular collagen matrix impregnated with antioxidants on the dynamics of oxidative stress in the conditions of wound process on 36 Wistar rats was carried out. An extracellular collagen matrix impregnated with ethylmethylhydroxypyridine succinate was implanted into the area of the created defect. The dynamics of the main indicators in the pro-oxidants-antioxidants system was evaluated on the 7th, 14th and 30th days after implantation. Results and conclusions. The animals of the main groups showed positive dynamics in restoring balance in the lipid peroxidation system. Thus, the use of antioxidants as part of the extracellular matrix and gel form makes it possible to neutralize the phenomena of oxidative stress in a shorter time.

Diabetes is a chronic disease associated with numerous complications including diabetic foot disorders, which are associated with significant morbidity and mortality as well as high costs. The costs associated with diabetic foot disorders comprise those linked to care (direct) and loss of productivity and poor quality of life (indirect). Due to the constant increase in diabetes prevalence, it is expected that diabetic foot disorder will require more resources, both in terms of caregivers and economically. We reviewed findings on management, morbidity, mortality, and costs related to diabetic foot disorder.

Aims: Diabetic foot syndrome (DFS) and its complications are a growing public health concern. The Italian Society of Diabetology (SID) and the Italian Association of Clinical Diabetologists (AMD), in collaboration with other scientific societies, will develop the first Italian guidelines for the treatment of DFS. Methods: The creation of SID/AMD Guidelines is based on an extended work made by 19 panelists and 12 members of the Evidence Review Team. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology has been used to decide aims, reference population, and target health professionals. Clinical questions have been created using PICO (Patient, Intervention, Comparison, Outcome) conceptual framework. The definition of questions has been performed using a two-step web-based Delphi methodology, a structured technique aimed at obtaining by repeated rounds of questionnaires a consensus opinion from a panel of experts in areas wherein evidence is scarce or conflicting, and opinion is important. Results: The mean age of panelists (26.3% women) was 53.7 ± 10.6 years. The panel proposed 34 questions. A consensus was immediately reached for all the proposed questions, 32 were approved and 2 were rejected. Conclusions: The areas covered by clinical questions included diagnosis of ischemia and infection, treatment of ischemic, neuropathic, and infected ulcers, prevention of foot ulceration, organization and education issues, and surgical management. The PICO presented in this paper are designed to provide indications for healthcare professionals in charge of diabetic foot treatment and prevention, primarily based on clinical needs of people with diabetic foot syndrome and considering the existing organization of health care. [ABSTRACT FROM AUTHOR]

Diabetic foot syndrome (DFS) is one of the most serious macroangiopathic complications of diabetes. The primary treatment option is revascularization, but complementary therapies are still being sought. The study group consisted of 18 patients diagnosed with ischemic ulcerative and necrotic lesions in DFS. Patients underwent revascularization procedures and, due to unsatisfactory healing of the lesions, were randomly allocated to two groups: a group in which bicistronic VEGF165/HGF plasmid was administered and a control group in which saline placebo was administered. Before gene therapy administration and after 7, 30, 90, and 180 days, color duplex ultrasonography (CDU) was performed, the ankle-brachial index (ABI) and transcutaneous oxygen pressure (TcPO2) were measured, and DFS changes were described and documented photographically. In the gene therapy group, four out of eight patients (50%) healed their DFS lesions before 12 weeks. During this time, the ABI increased by an average of 0.25 and TcPO2 by 30.4 mmHg. In the control group, healing of the lesions by week 12 occurred in six out of nine patients (66.67%), and the ABI increased by an average of 0.14 and TcPO2 by 27.1 mmHg. One major amputation occurred in each group. Gene therapy may be an attractive option for complementary treatment in DFS. [ABSTRACT FROM AUTHOR]

Trophic ulcers (TU) associated with venous circulation pathology or diabetes mellitus are considered chronic wounds with all the attributes of the complex extracellular matrix (ECM) reorganization and tissue remodelling of the edges and bed of these wounds. It was therefore determined that only a comprehensive step-wise approach to the treatment of TU can produce a stable clinical result. The article presents the experience of comprehensive management of venous and diabetic TUs. Three clinical cases of management of patients with lower limb TUs are described. The treatment of patients was planned taking into account the accepted algorithms for the management of TU associated venous circulation pathology or diabetes mellitus. The topical therapy included advanced wound coverings. The choice of dressing was determined by the clinical course of wound process. Alginate dressings were used on stages I and II wounds; hydrocolloid dressings were used on stages II and III wounds. Effects resulting from treatment included almost complete healing or readiness of a TU for skin grafting. The topical therapy of venous and diabetic TUs is part of the comprehensive treatment. During phase 1 wound process, the topical drugs should have antimicrobial, necrolytic, draining, osmotic and analgesic action. During phase 2, the granulation tissue should be induced and the balanced moist environment should be created to promote tissue regeneration. The wound coverings specified in the above clinical examples are fully consistent with the principles of the TIME concept, their ease of use and comfort for the patient are pointed out.

Abstract Background Diabetic neuropathy is the most common microvascular complication of diabetes mellitus and a major risk factor for diabetes-related lower-extremity complications. Diffuse neuropathy is the most frequently encountered pattern of neurological dysfunction and presents clinically as distal symmetrical sensorimotor polyneuropathy. Due to the increasing public health significance of diabetes mellitus and its complications, screening for diabetic peripheral neuropathy is essential. Consequently, a review of the principles that guide screening practices, especially in resource-limited clinical settings, is urgently needed. Main body Numerous evidence-based assessments are used to detect diabetic peripheral neuropathy. In accordance with current guideline recommendations from the American Diabetes Association, International Diabetes Federation, International Working Group on the Diabetic Foot, and National Institute for Health and Care Excellence, a screening algorithm for diabetic peripheral neuropathy based on multiphasic clinical assessment, stratification according to risk of developing diabetic foot syndrome, individualized treatment, and scheduled follow-up is suggested for use in resource-limited settings. Conclusions Screening for diabetic peripheral neuropathy in resource-limited settings requires a practical and comprehensive approach in order to promptly identify affected individuals. The principles of screening for diabetic peripheral neuropathy are: multiphasic approach, risk stratification, individualized treatment, and scheduled follow-up. Regular screening for diabetes-related foot disease using simple clinical assessments may improve patient outcomes.

Objective ‒ to analyze the results of endovascular revascularization of the femoropopliteal segment with drug-eluting stents. Materials and methods. Endovascular intervention was performed in 23 patients with stenotic lesions of the superficial femoral artery (SFA). Paclitaxel-eluting stents were used. There were 10 men (43.5 %), 13 women (56.5 %). The mean age of the patients was (66.0 ± 3.5) years. There were 16 (69.6 %) patients with diabetes mellitus type 2 and diabetic angiopathy, and 7 (23.4 %) patients had obliterating atherosclerosis of the arteries of the lower limbs. Critical ischemia of the lower extremities was diagnosed in 18 (56.5 %) cases, intermittent claudication ‒ in 5 (21.7 %). Isolated lesions of the femoral-popliteal segment were noted in 3 (13.4 %) patients, lesions of the iliac and femoral-popliteal segments ‒ in 4 (17.4 %), lesions of the femoral-popliteal and ankle segments ‒ in 16 (69.6 %). Results. Twenty (86.6 %) scheduled procedures for stenting of the SFA were technically successful. Among postoperative complications, 3 (13.04 %) patients had puncture site hematomas that did not require surgical evacuation. In 6 (26.1 %) patients, signs of reperfusion syndrome were observed, which were treated with conservative treatment. During follow-up period (3 months), there were no cases of reocclusion or clinically significant restenosis at the stented level. In 1 (5.0 %) case, a hemodynamically significant stenosis of the SFA was observed outside the implanted stent. The patient successfully underwent angioplasty of SFA stenosis. There were no «major» amputations during follow-up period. «Small» ankle amputations were performed in 7 (35.0 %) patients with diabetic gangrene, where endovascular revascularization of the femoro-popliteal and ankle segments was the stage of surgical treatment. Conclusions. Implantation of drug-eluting stents is an effective method of endovascular revascularization in patients with SFA lesions. To compare the results of implantation of drug-eluting stents with other methods of revascularization of the lesions of the femoro-popliteal segment, it is necessary to accumulate more data and increase the duration of the follow-up period.

Peripheral arterial disease (PAD)-induced ischemia is an important component of diabetic foot syndrome (DFS). The results of revascularization of the lower extremity arteries (including percutaneous transluminal angioplasty [PTA]) do not always give satisfactory long-term results, which is due to many factors. The aim of the study was to investigate the alterations in selected circulating angiogenic factors and microcirculation parameters in 41 patients with DFS following PTA and analyze their relationships with clinical outcomes during 1-year follow-up. Our study revealed a general decrease in pro-angiogenic factor levels after PTA and their subsequent stabilization during subsequent observation. The results indicated a significant association between plasma circulating FGF-2 level and poor outcomes (including the incidence of restenosis/reocclusion of treated arteries) during 12 months of observation. The perioperative changes in FGF-2 showed a significant association with LDF alterations after PTA. Follow-up 1–3 months post-intervention showed a tendency towards elevated TcpO2, VEGF-A, and VEGF-R2 levels in patients free from adverse events. These results may provide a basis for further research on the potential use of selected circulating angiogenic factors for monitoring the treatment of patients with DFS following PTA. [ABSTRACT FROM AUTHOR]

Introduction: The formation of hard-to-heal wounds can have many causes and is most often the result of the influence of several patient health factors. Some of the most difficult to treat effectively are wounds resulting from complications of diabetes, known as diabetic foot syndrome. Material and methods: Fifty-two patients (mean age 67 years ± 11.5) were eligible. All patients had chronic wounds of varied etiology in the lower limb, the previous treatment of which had not been satisfactory. Therapy parameters were selected individually; in addition to standard therapy, topical physical agents such as light therapy, pulsed electromagnetic field, ozone therapy, and oxygen therapy were included in the treatment. Each therapeutic cycle lasted 10 consecutive days (excluding Saturdays and Sundays), and each treatment lasted approximately 1 hour. Results: The analgesic effect of PEMF therapy was reported at 60% according to the VAS scale assessment. Pain was reduced from the third day of treatments, including for patients in whom pharmacological pain relief did not produce a clear improvement. Wound improvement, through granulation, after the first 10-day treatment cycle was observed in 40.5% of patients (14 k, 7 m). Four patients dropped the continuation of treatment because they did not see healing progress. Six patients dropped out of the next treatment cycle for other reasons (high cost of therapy, long distance of the clinic from home, and other socio-economic reasons). Conclusions: The high efficiency of combining standard treatment with innovative physical treatments allows for better patient care, which accelerates the necessary therapeutic steps toward holistic patient treatment. The authors recommend further multicenter, randomized, blinded trials to develop the optimal dosage to maximize the therapeutic effect and shorten the time to complete wound closure. [ABSTRACT FROM AUTHOR]

Diabetic foot syndrome (DFS) is an external symptom of diabetes mellitus that has been ongoing for many years, usually uncontrolled. Systemic treatment must be carried out in parallel with local treatment. The basic element of the therapy is a diagnosis, followed by implementation of causal treatment and proper local management. Because of the increased risk of malnutrition in this group of patients, many studies also indicate the need to implement nutritional treatment. Therefore, in the comprehensive treatment of a patient with DFS, it is also advisable to educate the patient and their family about nutrition and encourage them to choose better nutritional options. This paper presents 2 case reports of patients with DFS in whom nutritional intervention was implemented. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effectiveness of combined negative pressure wound therapy (NPWT) and human amniotic membrane in patients with chronic wounds associated with diabetes. A total of five patients with type 2 diabetes, including ischemic and mixed forms of diabetic foot syndrome, presenting with ischemic wounds of the lower extremities were included in this study. Patients with uncorrected limb ischemia were excluded. The treatment protocol included diabetes compensation (treatment with fractional insulin therapy), anticoagulant, metabolic therapy and angiotropic therapy, physical treatment methods, osteoporosis therapy with calcium preparations, and wound-specific interventions. The primary treatment approach involved the application of a vacuum bandage to the transplanted human amniotic membrane, which improved the adaptation of the flap to the wound surface, allowed the removal of excess wound exudate, and stimulated angiogenesis and reparative properties. The combined approach of NPWT and biotherapy was a safe and effective cure for diabetic wounds, promoting faster wound healing, reducing the need for autodermoplasty, and possibly reducing the necessity for high-level amputations. [ABSTRACT FROM AUTHOR]

Background: In the present study, we aimed to identify risk factors for failure (defined as reoperation within 60 days) after debridement or amputation at the lower extremity in patients with diabetic foot syndrome and to develop a model using the significant risk factors to predict the success rate at different levels of amputation. Methods: Between September 2012 and November 2016, we performed a prospective observational cohort study of 174 surgeries in 105 patients with diabetic foot syndrome. In all patients, debridement or the level of amputation, need for reoperation, time to reoperation, and potential risk factors were assessed. A cox regression analysis, dependent on the level of amputation, with the endpoint reoperation within 60 days defined as failure and a predictive model for the significant risk factors were conducted. Results: We identified the following 5 independent risk factors: More than 1 ulcer (hazard ratio [HR] 3.8), peripheral artery disease (PAD, HR 3.1), C-reactive protein >100 mg/L (HR 2.9), diabetic peripheral neuropathy (HR 2.9), and nonpalpable foot pulses (HR 2.7) are the 5 independent risk factors for failure, which were identified. Patients with no or 1 risk factor have a high success rate independent of the level of amputation. A patient with up to 2 risk factors undergoing debridement will achieve a success rate of <60%. However, a patient with 3 risk factors undergoing debridement will need further surgery in >80%. In patients with 4 risk factors a transmetatarsal amputation and in patients with 5 risk factors a lower leg amputation is needed for a success rate >50%. Conclusion: Reoperation for diabetic foot syndrome occurs in 1 of 4 patients. Risk factors include presence of more than 1 ulcer, PAD, CRP > 100, peripheral neuropathy, and nonpalpable foot pulses. The more risk factors are present, the lower the success rate at a certain level of amputation. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the clinical effectiveness of the use of bioplastic collagenous material Collost in the treatment of chronic wounds in patients with diabetic foot syndrome (DFS). Material and methods. The study involved 35 patients with DFS having chronic wounds on the lower extremities accompanied by type 2 diabetes mellitus. Patients with DFS in the comparison group received standard treatment. In the main group, standard treatment was supplemented with local application of Collost collagen biomaterial in the form of a membrane of different size depending on the area of the wound surface. The mobile Wound Analysis application (USA) evaluated the quantitative characteristics of the wound surface. Results. On the 28th day of treatment, a significant difference between the groups (p0.05) from 1.59 cm2 to 1.03 cm2 (1.54 times) due to the cases of complete epithelization of wound surfaces, in the comparison group it increased (p>0.05) from 1.85 cm2 to 2.25 cm2 (1.21 times). Conclusions. The use of Collost collagen biomaterial in patients with DFS after 28 days of treatment leads to a more significant reduction 2.29 times in the total area of the wound surface of chronic wounds, 4.12 times decrease in the area of purulent-fibrin plaque, a three-fold increase in the frequency of cases of complete epithelialization of the wound. The use of collagen containing biomaterials in the complex treatment of patients with DFS exerts a positive effect on the dynamics of the wound process in chronic wounds.

Despite clear evidence of inadequate angiogenesis in ischemic diabetic foot syndrome (DFS) pathogenesis, angiogenic factor level changes in patients with ischemic DFS remain inconsistent. This study aimed to assess circulating angiogenic factors concerning ischemic DFS advancement and describe their relationships with patients' clinical characteristics, microvascular parameters, and diabetic control. The study included 41 patients with ischemic DFS (67.3 (8.84) years; 82.9% males). Angiogenic processes were assessed by identifying circulating concentrations of five pro- and two anti-angiogenic factors. We found that penetrating ulcers were related to a significantly higher FGF-2 level (8.86 (5.29) vs. 5.23 (4.17) pg/mL, p = 0.02). Moreover, plasma FGF-2 showed a significant correlation with the SINBAD score (r = 0.32, p = 0.04), platelet count (r = 0.43, p < 0.01), white cell count (r = 0.42, p < 0.01), and age (r = −0.35, p = 0.03). We did not observe any significant linear relationship between the studied biomarkers and microcirculatory parameters, nor for glycemic control. In a univariate analysis using logistic regression, an increase in plasma FGF-2 was tied to greater odds of high-grade ulcers (OR 1.16; 95% CI 1.02–1.38, p = 0.043). This suggests that circulating FGF-2 may serve as a potential biomarker for predicting DFU advancement and progression. It is necessary to conduct further studies with follow-up observations to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Diabetic foot syndrome (DFS) is a complication associated with diabetes that has a strong negative impact, both medically and socio-economically. Recent epidemiological data show that one in six patients with diabetes will develop an ulcer in their lifetime. Vascular complications associated with diabetic foot have multiple prognostic implications in addition to limiting functional status and leading to decreased quality of life for these patients. We searched the electronic databases of PubMed, MEDLINE and EMBASE for studies that evaluated the role of DFS as a cardiovascular risk factor through the pathophysiological mechanisms involved, in particular the inflammatory ones and the associated metabolic changes. In the era of evidence-based medicine, the management of these cases in multidisciplinary teams of "cardio-diabetologists" prevents the occurrence of long-term disabling complications and has prognostic value for cardiovascular morbidity and mortality among diabetic patients. Identifying artificial-intelligence-based cardiovascular risk prediction models or conducting extensive clinical trials on gene therapy or potential therapeutic targets promoted by in vitro studies represent future research directions with a modulating role on the risk of morbidity and mortality in patients with DFS. [ABSTRACT FROM AUTHOR]

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The article presents a morphological evaluation of the effectiveness of the use of silver sulfathiazole (SST) in the local treatment of trophic ulcers in patients with diabetic foot syndrome (DFS). It has been shown that the use of SST in local therapy in DFS patients can improve the course of the wound process and stimulate regeneration processes. The quantitative discrepancies that were found in the expression levels of CD68+ macrophages, depending on the nature of the local therapy in DFS patients, are a diagnostic criterion for the clinical efficacy of using SST in the complex treatment of this category of patients.

Diabetic foot syndrome is a secondary disease of diabetes mellitus that can lead to amputations, reduced mobility and in some cases death if treatment is delayed. The objective of this study was to collect user requirements for the development of a shoe insole accompanied by a medical app for continuous pressure measurement, applying a usercentered Design Thinking process.We conducted a systematic competitor analysis and performed 10 context-interviews with both health care professionals (HCPs) (n=7) and patients with diabetic foot syndrome (n=3) at the University Hospital Graz (Austria) and a medical supply store. Structured interview guides, tailored to user groups were used for qualitative interviews. Questionnaires on the acceptance of eHealth applications were designed for quantitative analysis (n=14 patients, n=7 HCPs). The competitor analysis identified 12 inshoe- systems for plantar pressure measurement for patients with diabetes. No current system on the EU market meets the requirements of the users interviewed in this study. Quantitative evaluation showed that 95% of future users would support the use of a medical app to monitor plantar pressure in patients with diabetic foot syndrome. Based on the identified user requirements, a first user interface was developed iteratively. Usability tests of the prototype resulted in a score of 71.7 on the System Usability Scale. The medical app will be further developed and tested in clinical studies.

Introduction One of the complications of diabetes mellitus is Charcot's osteoarthropathy, associated with the development of angio-neuropathic and metabolic disorders in the foot and loss of limb weight-bearing. Its association with purulent infection not only worsens the quality of life of patients, but also poses a threat to life. The literature reports very conflicting information about the choice of reconstruction technologies and methods of foot fixation. The lack of unified approaches and generally recognized protocols indicates the dissatisfaction of orthopedists with the results achieved and the imperfection of the technologies used. The aim of the work is to evaluate the effectiveness of the combined use of the Masquelet technology and Ilizarov transosseous osteosynthesis in Charcot osteoarthropathy in conditions of purulent infection. Material and methods The authors present an original approach to foot reconstruction in 8 patients, based on the combined use of the Masquelet technology and Ilizarov transosseous osteosynthesis. The follow-up period ranged from 1 to 11 months from the date of the primary operation. Results In all patients treated by this technique, the limb support was restored. Nonunion, loss of correction, and late infection complications were not detected. Discussion The combined use of transosseous osteosynthesis allows discrete correction of multicomponent foot deformities without creating additional angiotrophic disorders, and the use of Masquelet bone grafting to sanitize pathologically altered tissues with the formation of an induced membrane that produces growth factors and has antimicrobial activity. Choosing the tactics of treatment for preservation of the foot as an organ in patients with severe condition of the feet with Charcot osteoarthropathy, the method of two-stage surgical treatment is justified and provides length compensation of the segments, limb support even in cases where, at first glance, amputation has relative indications. Conclusion Differentiated application of the Ilizarov and Masquelet technologies is effective and justified in conditions of Charcot's arthropathy.

Introduction. The risk of infectious complications in patients with diabetic foot syndrome (DFS) is 25.2 to 58%, the risk of hospitalization among the patients with complications of DFI is 56 times, and the risk of amputation is 155 times higher than non-diabetics. Detection of the etiologic agent has a crucial role in effective treatment, prevention of dissemination of the infection, and avoiding amputation.Aim of the study: to analyze the specific characteristics of the severe diabetic foot infection and antibiotic resistance of the pathogens during the inpatient and outpatient stages of treatment.Materials and methods. We included 62 type 2 diabetic inpatients (38 male and 24 female, group 1) with severe foot infection in to the study. 102 diabetic foot outpatients (56 male and 46 female, group 2) with postoperative wounds were included after discharged from the hospital. Cultures were obtained after surgery interventions immediately and on 14 days of hospitalization in group 1 of patients and in group 2 of patients with clinical signs of infection. Microbe species and resistant of pathogens to antibiotic were assessed.Results. There were prevalence of multidrug resistant Staphilococcus aureus (MRSA), Enterobacterales and Acinetobacter baumannii both outpatient and inpatient stages of diabetic foot infections treatment. The multidrug resistant pathogens were associated with ineffective empiric antibiotic therapy, delay of wound healing and amputations. The presence of multidrug resistant pathogens should be expected in cases of wound size more than 18 sm2, history of diabetic foot amputations, chronic osteomyelitis and time before wound professional care more than 14 weeks.Conclusion. The multidrug resistant pathogens were the main risk factor of amputations in diabetic foot inpatients with severe infections. At the outpatient stage of treatment multidrug resistant pathogens along with chronic osteomyelitis lead to delay of wound healing and new cases of foot amputations in diabetic patients.

The objective was to evaluate the efficacy and safety of closed transosseous osteosynthesis in the treatment of patients with diabetic Charcot neuroosteoarthropathy at the acute radiographically positive stage (Eichenholtz 1-2) with hindfoot and midfoot deformity and immobilization using Total Contact Cast. Material and methods Eight patients of the treatment group underwent closed deformity correction and Ilizarov external fixation. The frame was removed with radiographic signs of consolidation and conservative methods of fixation and off-loading employed. The control group consisted of 11 patients who received outpatient conservative treatment with Total Contact Cast combined with crutches. Results The treatment length of surgical patients prior to the use of orthopaedic shoes was shorter than that of patients treated conservatively. Foot ulcers seen in the conservative group during the observation period were not detected in the surgical cases and were associated with the lack of deformity correction. Discussion The advantage of operative reconstruction includes more stable foot and lower risk of ulcers. Reduced rehabilitation period improves the patient's quality of life. Complications that developed in the treatment group were resolved and had no effect on the outcome. Conclusion Closed deformity correction using transosseous osteosynthesis can be an option for patients with diabetic Charcot neuroosteoarthropathy at the acute radiographically positive stage as compared to the conservative treatment.

Background: Diabetic neuropathy is the most common microvascular complication of diabetes mellitus and a major risk factor for diabetes-related lower-extremity complications. Diffuse neuropathy is the most frequently encountered pattern of neurological dysfunction and presents clinically as distal symmetrical sensorimotor polyneuropathy. Due to the increasing public health significance of diabetes mellitus and its complications, screening for diabetic peripheral neuropathy is essential. Consequently, a review of the principles that guide screening practices, especially in resource-limited clinical settings, is urgently needed. Main body: Numerous evidence-based assessments are used to detect diabetic peripheral neuropathy. In accordance with current guideline recommendations from the American Diabetes Association, International Diabetes Federation, International Working Group on the Diabetic Foot, and National Institute for Health and Care Excellence, a screening algorithm for diabetic peripheral neuropathy based on multiphasic clinical assessment, stratification according to risk of developing diabetic foot syndrome, individualized treatment, and scheduled follow-up is suggested for use in resource-limited settings. Conclusions: Screening for diabetic peripheral neuropathy in resource-limited settings requires a practical and comprehensive approach in order to promptly identify affected individuals. The principles of screening for diabetic peripheral neuropathy are: multiphasic approach, risk stratification, individualized treatment, and scheduled follow-up. Regular screening for diabetes-related foot disease using simple clinical assessments may improve patient outcomes. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNP) in the RAC1 (Rac family small GTPase 1) gene have recently been linked to type 2 diabetes (T2D) and hyperglycemia due to their contribution to impaired redox homeostasis. The present study was designed to determine whether the common SNPs of the RAC1 gene are associated with diabetic complications such as neuropathy (DN), retinopathy (DR), nephropathy, angiopathy of the lower extremities (DA), and diabetic foot syndrome. A total of 1470 DNA samples from T2D patients were genotyped for six common SNPs by the MassArray Analyzer-4 system. The genotype rs7784465-T/C of RAC1 was associated with an increased risk of DR (p = 0.016) and DA (p = 0.03) in males, as well as with DR in females (p = 0.01). Furthermore, the SNP rs836478 showed an association with DR (p = 0.005) and DN (p = 0.025) in males, whereas the SNP rs10238136 was associated with DA in females (p = 0.002). In total, three RAC1 haplotypes showed significant associations (FDR < 0.05) with T2D complications in a sex-specific manner. The study's findings demonstrate, for the first time, that the RAC1 gene's polymorphisms represent novel and sex-specific markers of neuropathy and microvascular complications in type 2 diabetes, and that the gene could be a new target for the pharmacological inhibition of oxidative stress as a means of preventing diabetic complications. [ABSTRACT FROM AUTHOR]

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Vitamin D is a very important prohormone that needs for maintaining homeostasis and harmonious work of the endocrine system. This review article shows the impact of vitamin D on diabetes mellitus and its complications, such as diabetic retinopathy, nephropathy, neuropathy, and diabetic foot. The authors used databases PubMed and Google Scholar to find literature data. The review determines the benefits of vitamin D supplements to correct mineral, carbohydrate, and lipid metabolism. The results of several meta-analyses are presented, which both confirm the relationship between vitamin D deficiency and diabetes mellitus or doubt its existence. The probable mechanisms of vitamin D influence on the development of diabetic retinopathy at the cellular and molecular levels are highlighted. In particular, the effect of this vitamin on the immune system through the regulation of cytokine levels is demonstrated. A significant association between vitamin D deficiency and the development of diabetic peripheral neuropathy has been shown. The effect of vitamin D supplements on renal function, inflammation, and glycemic control in patients with diabetic kidney disease has been demonstra­ted. The authors analyzed the effect of vitamin D compared with other nutrients on the treatment of diabetic foot ulcers. The importance of vitamin D for improving glycemic control and wound healing is emphasized. In conclusion, the screening of patients with diabetes mellitus for vitamin D deficiency and the use of this supplement to prevent and treat microvascular and macrovascular diabetic complications are recommended. Randomized, placebo-controlled, double-blind clinical trials are promising to further investigate the mechanisms of vitamin D exposure and determine the appropriate adequate dose for patients with diabetes mellitus and its complications.

Context: Living with diabetes can be difficult since it can affect the patient in many ways. Diabetic foot syndrome (DFS) is described as a group of symptoms where neuropathy reduced blood supply and infection leads to tissue breakdown and morbidity. Aim: This study aims to determine the prevalence of DFS and associated sociodemographic and treatment-related factors among adults living with type 2 diabetes mellitus in a rural community. Setting and Design: A cross-sectional study was conducted in an area under the rural health training centre of department of Community Medicine. Methods and Material: The study was conducted to determine DFS by measuring neuropathy, peripheral vascular disease using Michigan neuropathy screening instrument, and clinical examination. Statistical Analysis Used: The data collected was analyzed using SPSS 25. Results: The prevalence of DFS among those with type 2 diabetes mellitus was high (51.7%). DFS was associated with advanced age (>75 years), duration of diabetes for more than 5 years and with foot ulcer. Smoking and alcohol consumption were not associated with DFS. Conclusion: Half of those with diabetes had DFS. People with DFS were more likely to be older and living with diabetes for longer duration. This underscores the need for early identification of DFS by the primary care physicians. Further research on the role of health professionals at the primary care level in educating and screening DFS in people with diabetes are required.

Diabetic foot ulcers are an extremely urgent medical and social problem throughout the world. The purpose of this study was to analyse the histological and immunohistochemical features of tissues and cells of different sections of wounds taken during the primary surgical treatment of chronic wounds in patients with diabetic foot syndrome with favourable and unfavourable outcomes. Material and methods. A clinical prospective observational study of the treatment outcomes of fifty-three patients with diabetic foot ulcers hospitalized twice in one specialized centre over the course of the year was conducted. The analysis of histological and immunohistochemical data of the tissues of the edges and the centre of the ulcer taken during the primary surgical treatment was performed. While performing histological analyses of wound tissues, special attention was given to the determination of cellular characteristics of leukocyte-necrotic masses, granulation tissue, and loose and dense connective tissue. Immunohistochemistry was performed using a set of monoclonal antibodies, allowing verification of neutrophilic leukocytes, fibroblasts, and endothelial cells. Results. Unfavourable outcomes (amputation, reamputation, death from cardiovascular diseases, nonhealing ulcer within a year) were registered in 52.8% of cases. Uniform distribution of neutrophils and endothelial cell fibroblasts in all parts of the wound was recorded in patients with a favourable outcome. An unfavourable outcome was predetermined by the uneven content of these cells with a significant increase in neutrophilic leukocytosis in the bottom of the wounds, as well as a significant decrease in the number of fibroblasts and endotheliocytes in the centre of the wounds. Conclusions: The datasets obtained during primary surgical treatment are extremely informative to predict the outcome of the treatment of diabetic foot ulcers and indicate more active surgical strategies with the potential to reduce the treatment time, increase its effectiveness, and eventually make the treatment cost-effective. [ABSTRACT FROM AUTHOR]