Identification and validation of novel inflammatory response-related diagnostic biomarkers in diabetic foot ulcers.

Integrated analysis of circRNA-miRNA-mRNA regulatory network identifies potential diagnostic biomarkers in diabetic foot ulcer.

Objective: To screen the differentially expressed genes (DEGs) in diabetic foot ulcers (DFUs), and to perform functional analysis and clinical validation of them, intending to lay a theoretical foundation for epigenetic therapy of chronic refractory wounds. Methods: An observational study was conducted. The gene expression profile dataset GSE80178 of DFU patients in Gene Expression Omnibus (GEO) was selected, and the DEG between three normal skin tissue samples and six DFU tissue samples in the dataset was analyzed and screened using the GEO2R tool. For the screened DEG, ClusterProfiler, org.Hs.eg.db, GOplot, and ggplot2 in the R language packages were used for Gene Ontology (GO) enrichment analysis of biological processes, molecular functions, and cellular components, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, respectively. Protein-protein interaction (PPI) analysis was performed using STRING database to screen key genes in the DEG, and GO enrichment analysis of key genes was performed using Cytohubba plug-in in Cytoscape 3.9.1 software. DFU tissue and normal skin tissue discarded after surgery were collected respectively from 15 DFU patients (7 males and 8 females, aged 55-87 years) and 15 acute wound patients (6 males and 9 females, aged 8-52 years) who were admitted to Xiang'an Hospital of Xiamen University from September 2018 to March 2021. The mRNA and protein expressions of small proline-rich repeat protein 1A (SPRR1A) and late cornified envelope protein 3C (LCE3C) were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Data were statistically analyzed with independent sample t test. Results: Compared with normal skin tissue, 492 statistically differentially expressed DEGs were screened from DFU tissue of DFU patients (corrected P<0.05 or corrected P<0.01), including 363 up-regulated DEGs and 129 down-regulated DEGs. GO terminology analysis showed that DEGs were significantly enriched in the aspects of skin development, keratinocyte (KC) differentiation, keratinization, epidermal development, and epidermal cell differentiation, etc. (corrected P values all <0.01). KEGG pathway analysis showed that DEGs were significantly enriched in the aspects of tumor-associated microRNA, Ras related protein 1 signaling pathway, and pluripotent stem cell regulatory signaling pathway, etc. (corrected P values all <0.01). PPI analysis showed that endophial protein, SPRR1A, SPRR1B, SPRR2B, SPRR2E, SPRR2F, LCE3C, LCE3E, keratin 16 (all down-regulated DEGs), and filoprotein (up-regulated DEG) were key genes of DEGs screened from DFU tissue of DFU patients, which were significantly enriched in GO terms of keratinization, KC differentiation, epidermal cell differentiation, skin development, epidermis development, and peptide cross-linking, etc. (corrected P values all <0.01). The mRNA expressions of SPRR1A and LCE3C in DFU tissue of DFU patients were 0.588±0.082 and 0.659±0.098, respectively, and the protein expressions were 0.22±0.05 and 0.24±0.04, respectively, which were significantly lower than 1.069±0.025 and 1.053±0.044 (with t values of 20.91 and 13.66, respectively, P values all <0.01) and 0.38±0.04 and 0.45±0.05 (with t values of 9.69 and 12.46, respectively, P values all <0.01) in normal skin tissue of acute wound patients. Conclusions: Compared with normal skin tissue, there is DEG profile in DFU tissue of DFU patients, with DEGs being significantly enriched in the aspects of KC differentiation and keratin function. Key DEGs are related to the biological function of KC, and their low expressions in DFU tissue of DFU patients may impede ulcer healing.

Chronic wounds, including pressure sores, leg ulcers, diabetic foot ulcers and other kinds of wounds, healing by secondary intention are common in both acute and community settings. The prevention and treatment of chronic wounds includes many strategies, including the use of various wound dressings, bandages, antimicrobial agents, footwear, physical therapies and educational strategies. This review is one of a series of reviews, and focuses on the prevention and treatment of diabetic foot ulcers and the role of antimicrobial agents in chronic wounds in general. To assess the clinical- and cost-effectiveness of (1) prevention and treatment strategies for diabetic foot ulcers and (2) systemic and topical antimicrobial agents in the prevention and healing of chronic wounds. METHODS - DATA SOURCES: Nineteen electronic databases were searched, including MEDLINE, CINAHL, Embase and the Cochrane Library. Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched. An expert panel was consulted. Randomised and non-randomised trials with a concurrent control group, which evaluated any intervention for the prevention or treatment of diabetic foot ulcers, or systemic or topical antimicrobials for chronic wounds (diabetic foot ulcers, pressure ulcers, leg ulcers of various aetiologies, pilonidal sinuses, non-healing surgical wounds, and cavity wounds) and used objective measures of outcome such as: (1) development or resolution of callus; (2) incidence of ulceration (for diabetic foot ulcer prevention studies); (3) incidence of pressure sores (pressure sore prevention studies); (4) any objective measure of wound healing (frequency of complete healing, change in wound size, time to healing, rate of healing); (5) ulcer recurrence rates; (6) side-effects; (7) amputation rates (diabetic foot ulcer treatment studies); (8) healing rates and recurrence of disease, among others, for pilonidal sinuses. Studies reporting solely microbiological outcomes were excluded. Decisions on the inclusion of primary studies were made independently by two reviewers. Disagreements were resolved through discussion. Data were extracted by one reviewer into structured summary tables. Data extraction was checked independently by a second reviewer and discrepancies resolved by discussion. All included studies were assessed against a comprehensive checklist for methodological quality. INCLUDED STUDIES - DIABETIC FOOT ULCERS: Thirty-nine trials which evaluated various prevention and treatment modalities for diabetic foot ulcers: footwear (2), hosiery (1), education (5), screening and foot protection programme (1); podiatry (1) for the prevention of diabetic foot ulcers; and footwear (1), skin replacement (2), hyperbaric oxygen (2), ketanserin (3), prostaglandins (3), growth factors (5), dressings and topical applications (9), debridement (2) and antibiotics (2) for the treatment of diabetic foot ulcers. INCLUDED STUDIES - ANTIMICROBIALS: Thirty studies were included, 25 with a randomised design. There were nine evaluations of systemic antimicrobials and 21 of topical agents. The methodological and reporting quality was generally poor. Commonly encountered problems of reporting included lack of clarity about randomisation and outcome measurement procedures, and lack of baseline descriptive data. Common methodological weaknesses included: lack of blinded outcome assessment and lack of adjustment for baseline differences in important variables such as wound size; large loss to follow-up; and no intention-to-treat analysis. RESULTS - PREVENTION OF DIABETIC FOOT ULCERS: There is some evidence (1 large trial) that a screening and foot protection programme reduces the rate of major amputations. The evidence for special footwear (2 small trials) and educational programmes (5 trials) is equivocal. A single trial of podiatric care reported a significantly greater reduction in callus in patients receiving podiatric care. RESULTS - TREATMENT OF DIABETIC FOOT ULCERS: Total contact casting healed significantly more ulcers than did standard treatment in one study. There is evidence from 5 trials of topical growth factors to suggest that these, particularly platelet-derived growth factor, may increase the healing rate of diabetic foot ulcers. Although these studies were of relatively good quality, the sample sizes were far too small to make any definitive conclusions, and growth factors should be compared with current standard treatments in large, multicentre studies. Topical ketanserin increased ulcer healing rate in 2 studies, while systemic hyperbaric oxygen therapy reduced the rate of major amputations in 1 study. Preliminary research into the effects of iloprost and prostaglandin E1 (PGE1) on diabetic foot ulcer healing suggests possible benefits. However, good quality, large-scale confirmatory research is needed. (ABSTRACT TRUNCATED)

Introduction: Diabetes is one of the most prevalent metabolic chronic diseases due to the imbalance production of insulin. One of the studies reported that in 2010 worldwide 285 million adults had diabetes and this figure may be increase to 439 million by the year 2030. Globally Diabetic foot ulcers (DFUs) constitute major health problem in people that significantly contribute to morbidity and mortality in diabetes patients. Approximate 1.0% to 4.1% of the annual population-based incidences of a diabetic foot ulcer (DFU) were reported. Due to this the lifetime may be as high as 25%. In Asian countries diabetic foot ulcer are major problems which are different from European countries or developing countries. From many studies reported diabetic foot problems in India are infectious and neuropathic in nature as compared to developed countries. According to World Health Organization (WHO) diabetic foot is defined as lower limb of a diabetic patient characterized by infection, potential risk of pathologic consequences ulceration or destruction of deep tissues associated with neurological abnormalities, various changes in peripheral neuropathy vasculopathy and superimposed infection that are mainly responsible foot ulceration. Ulcers are one kind of abscess which is difficult to treat because of poor wound healing that result from a combination of neuropathy, ischemia and hyperglycemia. &#x0D; Aim: The main objective was to study the outcome of treatment modalities and it’s relating factors to complication in diabetic foot ulcer. Material and method: Total 60 diabetic foot ulcer patients with the age range from 20 to 70 years were included. From all the patients’ detailed past and present history were recorded. For all the patients, general, physical and local and systemic examinations were also done. Detail laboratory examination like Fasting and Post Prandial Blood sugar levels, blood count, ECG, ESR, complete urine examination for the presence of ketone bodies and sugar, x-ray as well as culture and sensitivity of the discharge from ulcer were also done. Patients were treated with various treatment methods like conservative treatment, split skin grafting and amputation.&#x0D; Result: In this study male patients were more in proportion as compared to female. This study showed that maximum with the age group 14 -50 (43.3%) years old followed by 18.3% in 31-40 years old, 16.7% in 61-70 years old. 6.7% showed the least age group as 20 -30 years old. Out of total 60 patients, 38.3% of the patients showed diabetic ulcer foot which was more whereas 15% showed diabetic gangrene foot which was least. 25% showed diabetic cellulites foot and 21.7% showed as diabetic abscess foot. &#x0D; Conclusion: Globally as diabetes mellitus cases are increasing and it became rapidly the public health problem. This may be due to burden on economy, health system and on society to manage the diabetic foot problems. Diabetic foot management guidelines must be made into our practice protocols which may preventing limb loss, and decrease mortality and increase the quality of life of the patient. Hence for this it is only possible with the help of foot care education and health care workers. Hence, foot infection is to put first and care for it like hands.&#x0D; Keywords: Diabetes, foot ulcers, infections, amputations.

Background: Many types of infection can cause diabetic foot ulcers Infections involving the bacteria; E. coli, Acinetobacter spp (MDR) and K. pneumoniae, pseudomonas aeruginosa, so the assessment of Bacterial profile and patterns is needed to understand the source and management of these injuries.&#x0D; Objective: To determine Bacterial infections profile and patterns for diabetic foot ulcers in nongovernmental.&#x0D; Method: During a period of eleven months, 148 patients with diabetic mellitus foot syndrome (DMFS). Patients were involved, out of 130 which foot ulceration infections. data analysis was done using SPSS version 20. p value was set at &lt;0.05.&#x0D; Results: Out of 607 Patients with diabetic foot ulceration (DFU) were 130 out of 148 with diabetic mellitus foot syndrome (DMFS). Diabetic foot ulceration (DFU) therefore contributed 20.3% of DMFS among these subjects. Microbiological culture pattern was total of 17 different pathogenic microorganisms were isolated from the participants, one yeast and 16 types of bacteria, from the diabetic foot swabs for ulcers. S. aureus was the most frequent pathogen followed by E.coli then Acinetobacter spp (MDR) and K. pneumonia, then pseudomonas aeruginosa , then p. mirabilis then Streptococcus agalactiae ( group b) then (Enitrobacteria spp and pseudomonas spp and Candida spp and P. vulgaris and K. oxytoca ESBL) then S. viridanse and Enterobacter spp ESBL and Staphylococcus coag. negative). The Enterobacter spp ESBL was the less frequent pathogen.&#x0D; Conclusion: Diabetic Foot Ulcerations (DFU), is forming about a quarter of the diabetic patient’s tissue infections, the causative agents were bacterial and fungal(yeast). Most of the causative pathogens were; Staphylococcus aureus, and Acinetobacter spp (MDR). The risk of development of High resistant drug isolates of diabetic foot ulcers to be multidrug resistance were high by 53% of total isolated pathogens specially with K. pneumonia (K. pneumoniae), Escherichia coli (E. coli) and Proteus mirabilis bacterial.

Diabetic foot ulcers (DFUs) is a severe complication of diabetes. Recent evidence suggests that ferroptosis, a form of regulated necrosis, may play a significant role in the progression of DFU. However, the precise molecular mechanisms remain elusive. This study aims to identify ferroptosis-related genes (FRGs) and the signaling pathways involved in DFU progression by analyzing the gene expression profiles of DFU. Differentially expressed genes (DEGs) were identified by analyzing gene expression data from two DFU-related datasets (GSE38396, and GSE143735). FRGs were collected from both datasets and the literature. DEGs were then intersected with FRGs to identify ferroptosis-related differentially expressed genes (FRDEGs) in DFU. Functional enrichment analysis, protein-protein interaction (PPI) network analysis, receiver operating characteristic (ROC) curve analysis, and regulatory network interaction analysis (including mRNA-miRNA, mRNA-transcription factor (TF), and mRNA-drug interactions) were performed on the FRDEGs. Additionally, immune infiltration analysis was conducted using CIBERSORTx. Finally, skin tissue samples from clinical patients were collected, and the expression levels of FRDEGs in DFU samples were validated through reverse transcription quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC) and Immunofluorescence (IF), to uncover potential new targets for the diagnosis and treatment of DFU. A total of 14 DFUs samples (non-healing group) and 12 control samples (healing group) were obtained in this study. We identified 276 DEGs in DFUs samples compared to controls, with 121 up-regulated and 155 down-regulated genes. By intersecting DEGs with ferroptosis-related genes, we identified 10 FRDEGs (AURKA, CTH, FBLN1, FTL, GLS2, KDM5C, MYH9, PCNA, PYCR1, and SPARC). The GO and KEGG analysis results showed that FRDEGs were mainly enriched in biological processes such as amino acid biosynthesis and tight junction pathways. Further analysis of FRDEGs identified ten hub genes closely associated with 112 TFs, 34 miRNAs, and 50 drugs or molecular compounds. Additionally, RT-qPCR validation of skin tissue samples from 8 DFU patients and 8 controls showed that AURKA were significantly up-regulated in DFU, IHC and IF analysis further demonstrated elevated AURKA protein expression in DFU samples. Moreover, AURKA was identified as a potential diagnostic marker for diabetic wound healing, with high diagnostic accuracy based on ROC curve analysis (AUC = 0.950 in the combined dataset, and AUC = 0.881 in the validation dataset). These findings highlight AURKA as a key gene involved in ferroptosis and a potential target for the diagnosis and monitoring of DFUs. This study identified FRDEGs associated with DFUs, highlighting AURKA as a key diagnostic marker. These findings offer valuable insights into the molecular mechanisms driving DFUs and suggest potential therapeutic targets for their management.

This study aims to investigate the molecular mechanisms by which quercetin facilitates the treatment of diabetic foot ulcers (DFU). Transcriptome sequencing datasets for DFU, specifically GSE80178, GSE134431, and GSE147890, along with single-cell dataset GSE165816, were retrieved from the Gene Expression Omnibus (GEO) online database (https://www.ncbi.nlm.nih.gov/geo/). The single-cell data were subjected to processing, annotation, differential gene expression analysis, and staining. The transcriptome sequencing data were analyzed using weighted gene co-expression network analysis (WGCNA), followed by assessment of immune infiltration. By integrating transcriptomic data and differentially expressed genes identified through WGCNA, co-expressed differentially expressed genes were obtained, and a protein-protein interaction (PPI) network was constructed followed by enrichment analysis. Core genes were screened using four machine learning models (Random Forest, Lasso, XGBoost, and SVM). Drug prediction was performed to identify potential therapeutic agents, and molecular docking simulations were conducted to assess the binding interactions between the macromolecular proteins encoded by the core genes and quercetin. A rat model of diabetic foot ulcer (DFU) was established and randomly divided into three groups: control, model, and treatment groups. Tissue samples were collected at 3, 7, and 14 days post-intervention for RT-qPCR, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and immunofluorescence staining to evaluate the therapeutic effects of quercetin via modulation of the core genes on DFU. The analysis identified 275 differentially co-expressed genes that are extensively involved in the IL-17 signaling pathway, metabolic pathways, the PI3K/Akt signaling pathway, Staphylococcus aureus infection, complement and coagulation cascades, among others. From these, four core genes (CIB2, SAMHD1, DPYSL2, IFI44) were selected using machine learning techniques. Immune infiltration analysis demonstrated a strong correlation between SAMHD1, IFI44, DPYSL2, and macrophages. Molecular docking studies revealed that quercetin exhibits a lower binding energy with the target protein binding site, forming a stable structure. Single-cell analysis indicated that SAMHD1 is predominantly expressed in macrophages, whereas DPYSL2 is expressed not only in macrophages but also significantly in vascular endothelial cells and other cell types. This suggests that SAMHD1 and DPYSL2 may exert their effects by modulating these cells, as corroborated by basic experimental findings. The improvement in wound tissue morphology observed in the treatment group was more favorable compared to the model group. In comparison to the acute group, the gene expression profile in the model group aligned with bioinformatics predictions. Furthermore, the alterations in core gene expression following quercetin treatment were statistically significant. Quercetin may enhance the healing of diabetic foot ulcers by modulating macrophage activity through the regulation of SAMHD1 and DPYSL2, thereby contributing to the recovery process.

Diabetes mellitus is the most common chronic disease that can lead to many clinical complications including vision, cardiac, and vascular disorders. Among vascular disorders, Diabetic foot ulcer (DFU) is a severe, fatal, serious and devastating complication and remained major economic consequences for the patients and country and is now a global public health issue. The prevalence of Diabetic foot ulcer in Western countries is 4–10% whereas the prevalence of Diabetic foot ulcer in the world is 15%. It has been reported that the healing rate of DFU is only 10–60% of patients after the first 3 months however the recurrence rate is 40%, 60%, and 71% after 1, 2, and 3 years, respectively. Limited treatment options are available for DFU patients. Stem cell therapy holds a great promise for treating Diabetic foot ulcer (DFU) and recently emerged as a new interventional strategy and appears to be cost-effective safe and effective in both preclinical and clinical trials. The most important characteristic for the successful utilization of mesenchymal stem cell treatments is the conducting of rapid and robust randomized controlled clinical trials. Diabetic foot ulcer remains the most important clinical challenge in the current medical practice and stem cell therapy may be an effective treatment for Diabetic foot ulcers. It is concluded that stem cell therapy is a potential, advanced, and effective treatment for Diabetic foot ulcers and is utilized as an alternative to amputation for T2D patients for revascularization. This therapy is utilizing tissue engineering as well as regenerative medicine.

Aim: - Serum inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), and procalcitonin (PCT), have been used for the diagnosis of foot infections in patients with diabetes. However, little is known about their changes during treatment of patients with foot infections. Procalcitonin (PCT) has been recently accepted as a marker for diagnosing infection. The aim of the present study was to determine whether PCT levels are associated with infection severity of diabetic foot ulcers and whether PCT levels would be helpful to differentiate infected diabetic foot ulcer (IDFU) from IDFU associated with other infectious diseases (IDFU + O). Methods: - This research was conducted in a Sardar Patel Medical College, Bikaner over the 2016 academic year. We prospectively included 95 diabetic patients hospitalized for IDFU. Infection severity of diabetic foot ulcers was graded according to the Infectious Diseases Society of America-International Working Group on the Diabetic Foot clinical classification of diabetic foot infection. Chest radiograph, urinalysis, urine microscopy, urine culture, and blood cultures (if fever was present) were performed for all patients to diagnose other infectious diseases. Laboratory parameters were measured from blood venous samples. Quantitative data from mid-year examination marks were analysed at the end of the academic year. Results: - PCT (0.286, P < 0.001) and C-reactive protein (0.368, P < 0.001) levels were significantly associated with infection severity of diabetic foot ulcers. However, only PCT levels could differentiate patients with associated infectious diseases from patients with no concomitant infection (area under the receiver-operator characteristic curve 0.729, P < 0.0001; cut-off value 0.44; sensitivity 88.7; specificity 70.2). Conclusion: -PCT and CRP levels positively correlated with infection severity of diabetic foot ulcers and PCT levels > 0.48 ng/mL in patients with IDFU may be associated with other systemic bacterial infection.

BACKGROUNDChronic nonhealing wounds, such as diabetic foot ulcer (DFU), suffer from delayed healing. Identifying effective biomarkers or targets is crucial for managing these refractory wounds. While N7-methylguanosine (m7G) methylation is important in RNA modification, its connection to chronic nonhealing wounds is poorly understood.AIMTo assess the potential m7G biomarkers in DFU and their underlying molecular mechanisms.METHODSDifferential expression analysis and weighted gene coexpression network analysis identified key genes in DFU. Hub genes were determined through m7G-DFU intersection, and gene set enrichment analysis was conducted. Diagnostic potential of hub genes was assessed using receiver operating characteristic curves. The hub gene’s expression (decapping scavenger enzyme, DCPS) was confirmed using quantitative reverse transcription polymerase chain reaction and immunofluorescence. In vitro, normal human epidermal keratinocyte models were knocked down for DCPS, and the function was assessed through flow cytometry, western blotting, immunofluorescence, Transwell assays, and scratch assays.RESULTSWeighted gene coexpression network analysis and differential expression analysis revealed links between DFU datasets and methylation processes, identifying hub gene DCPS as a candidate biomarker. Notably, its diagnostic value was confirmed with a test set and receiver operating characteristic curve, achieving an area under the curve of 0.98 and 0.99. Quantitative reverse transcription polymerase chain reaction and immunofluorescence analyses showed significantly reduced expression of DCPS in the wound skin of DFU patients and streptozotocin-induced diabetic mice, indicating its role as a regulatory factor of m7G in diabetic wounds. Mechanistically, in vitro studies showed that DCPS knockdown significantly reduced cyclin-dependent kinase 6 and cyclin D1 expression, disrupted the epithelial cell cycle, inhibited cell proliferation and migration, and increased apoptosis rates.CONCLUSIONDCPS was identified as a promising DFU biomarker and therapeutic target, regulating m7G to affect cell cycle, proliferation, and epithelial cell migration during DFU wound healing.

Diabetic foot ulcers (DFU) are chronic complications due to poor diabetic control. Diabetic foot ulcers can lead to lifelong disability and substantially diminish the quality of life. The aim of this study was to carry out a thorough evaluation of diabetic foot ulcer management, compare current scenario of DFUs care with the International guidelines and to identify the extended roles of clinical pharmacist to improve the conditions of diabetic patient with foot ulcers. It is a retrospective qualitative study carried out in two tertiary care hospitals of Tamil Nadu state. The patients were selected based on inclusion and exclusion criteria admitted in the hospitals with diabetic foot ulcers. The patient’s sociodemographic and clinical characteristics tools from the patient medication records (PMR) were collected and taken into considerations for the study. The study revealed that diabetic foot ulcer was more prevalent among male patients with type 2 diabetes since 11 to 25 yrs belongs to the age group between 51-60 years. It was found that 60.5% of the patients having at least one co-morbid condition and 90.6% of patients possess one or more risk factors to develop diabetic foot ulcers. Glycated hemoglobin (HbA1c) test were done only by 54.7% of the patients, which showed that it was not insisted as an important identification tool for diabetic foot ulcer. The PMR revealed numerous antibiotics switch-over for the wound treatment as well. From the study it was concluded that an immediate requirement and thorough evaluation of enhanced foot care management, patient centered care and diabetic foot surveillance etc is needed for diabetic foot ulcer management. A comparative current scenario of DFUs care with the International guidelines and its adaptation and modifications according to our need is to be emphasized. Amalgamation of clinical pharmacy services with the multidisciplinary diabetic foot care team services is to be made. The clinical pharmacist’s intervention is to be put forward to improve the conditions of diabetic patient with foot ulcers to decrease the alarming incidences in Indian hospital settings. Key Words: Diabetes, diabetic foot ulcer, wounds, guidelines, clinical pharmacy intervention

ABSTRAKDiabetic Foot Ulcer (DFU) termasuk kedalam salah satu komplikasi dari penyakit Diabetes Melitus yang mana kondisi ini merupakan masalah yang serius juga dapat menyebabkan kecacatan. Dampak merugikan pada ulkus kaki diabetik ialah biologis, psikologis, sosial ekonomi dan spiritual. Dampak psikologis yang sering terjadi pada pasien DFU ialah depresi. Depresi merupakan gangguan psikologis yang sering dikaitkan dengan stressor jangka panjang seperti penyakit kronis diantaranya diabetes melitus. Penelitian dilakukan berjutuan untuk mengetahui hubungan antara derajat DFU terhadap tingkat depresi pada pasien diabetes melitus di RSUD Dr.H.Moch Ansari Saleh Banjarmasin. Penelitian ini menggunakan metode kuantitatif dan menggunakan kuesioner sebagai alat pengupulan data. dengan jumlah 40 responden dengan Non-probability dengan teknik pengambilan sampel menggunakan Sampling Jenuh dengan semua menjadi sampel dengan jumlah 40 responden yang sedang menjalani rawat jalan dipoli kaki diabetik. Untuk alat ukur derajat dfu menggunakan kuesioner Diabetic Foot Ulcer Wegner dan kuesioner Back Depresion Inventory (BDII) untuk mengukur tingkat depresi. Hasil penelitian menjunjukan bahwa terdapat hubungan antara derajat diabetic foot ulcer terhadap tingkat depresi dengan hasil Sig. (2-tailed) (&lt;0,05), yang artinya adanya hubungan yang signifikan antara derajat diabetic foot ulcer terhadap tingkat depresi pada pasien diabetes melitus. Kata kunci: Diabetic Foot Ulcer, Tingkat Depresi ABSTRACTDiabetic Foot Ulcer (DFU) is one of the complications of Diabetes Mellitus, where this condition is a serious problem and can also cause disability. The detrimental impacts on diabetic foot ulcers are biological, psychological, socio-economic and spiritual. The psychological impact that often occurs in DFU patients is depression. Depression is a psychological disorder that is often associated with long-term stressors such as chronic diseases including diabetes mellitus. Several studies were conducted to determine the relationship between the degree of DFU and the level of depression in diabetes mellitus patients at Dr.H.Moch Ansari Saleh Hospital, Banjarmasin. This research uses quantitative methods and uses questionnaires as a data collection tool. with a total of 40 respondents with Non-probability with a sampling technique using Saturated Sampling with all being sampled with a total of 40 respondents who were undergoing outpatient treatment at the diabetic foot clinic. To measure the degree of dfu, Wegner's Diabetic Foot Ulcer questionnaire and the Back Depression Inventory (BDII) questionnaire are used to measure the level of depression. The results of the study showed that there was a relationship between the degree of diabetic foot ulcers and the level of depression and the Sig results. (2-tailed) (&lt;0.05), which means there is a significant relationship between the degree of diabetic foot ulcers and the level of depression in diabetes mellitus patients.Keywords: Diabetic Foot Ulcer, Depression Rate

Diabetic foot ulcers (DFU) are a devastating complication of diabetes. There are numerous challenges with preventing diabetic foot complications and barriers to achieving the care processes suggested in established foot care guidelines. Multi-faceted digital health solutions, which combine multimodal sensing, patient-facing biofeedback, and remote patient monitoring (RPM), show promise in improving our ability to understand, prevent, and manage DFUs. Patients with a history of diabetic plantar foot ulcers were enrolled in a prospective cohort study and equipped with custom sensory insoles to track plantar pressure, plantar temperature, step count, and adherence data. Sensory insole data enabled patient-facing biofeedback to cue active plantar offloading in response to sustained high plantar pressures, and RPM assessments in response to data trends of concern in plantar pressure, plantar temperature, or sensory insole adherence. Three non-consecutive case participants that ultimately presented with pre-ulcerative lesions (a callus and/or erythematous area on the plantar surface of the foot) during the study were selected for this case series. Across three illustrative patients, continuous plantar pressure monitoring demonstrated promise for empowering both the patient and provider with information for data-driven management of pressure offloading treatments. Multi-faceted digital health solutions can naturally enable and reinforce the integrative foot care guidelines. Multi-modal sensing across multiple physiologic domains supports the monitoring of foot health at various stages along the DFU pathogenesis pathway. Furthermore, digital health solutions equipped with remote patient monitoring unlock new opportunities for personalizing treatments, providing periodic self-care reinforcement, and encouraging patient engagement-key tools for improving patient adherence to their diabetic foot care plan.

INTRODUCTION: In this study, we explore the intricate domain of Diabetic Foot Ulcers (DFU) through the development of a comprehensive framework that encompasses diverse operational scenarios. The focus lies on the identification and classification assessment of diabetic foot ulcers, the implementation of smart health management strategies, and the collection, analysis, and intelligent interpretation of data related to diabetic foot ulcers. The framework introduces an innovative approach to predicting diabetic foot ulcers and their key characteristics, offering a technical solution for forecasting. The exploration delves into various computational strategies designed for intelligent health analysis tailored to patients with diabetic foot ulcers. OBJECTIVES: The primary objective of this paper is to present a technical solution for forecasting diabetic foot ulcers, utilizing computational strategies for intelligent health analysis. METHODS: Techniques derived from social network analysis are employed to conduct this research, focusing on diverse computational strategies geared towards intelligent health analysis for patients with diabetic foot ulcers. The study highlights methodologies addressing the unique challenges posed by diabetic foot ulcers, with a central emphasis on the integration of Internet of Medical Things (IoMT) in prediction strategies. RESULTS: The main results of this paper include the proposal of IoMT-based computing strategies covering the entire spectrum of DFU analysis, such as localization, classification assessment, intelligent health management, and detection. The study also acknowledges the challenges faced by previous research, including low classification rates and elevated false alarm rates, and proposes automatic recognition approaches leveraging advanced machine learning techniques to enhance accuracy and efficacy. CONCLUSION: The proposed IoMT-based computing strategies present a significant advancement in addressing the challenges associated with predicting diabetic foot ulcers. The integration of advanced machine learning techniques demonstrates promise in improving accuracy and efficiency in diabetic foot ulcer localization, marking a positive stride towards overcoming existing limitations in previous research.

Objectives: Patients with Diabetic Kidney Disease (DKD) and foot ulcer have poor prognosis. However, no study have found association of diabetic foot ulcer (DFU) with diabetic kidney dysfunction and their co-existing risk factors. Materials and Methods: This cross sectional study collected the data for 10,680 patients for 15 years. All variables were analyzed biochemically and statistically by standardized methodology. Results: Levels of HbA1c, creatinine, systolic and diastolic blood pressures, microalbuminuria, spot urine protein, and spot urine protein to creatinine ratio were higher among the groups with foot ulcers (p-value &lt; 0.0001 for all). Average ABI was observed to be lower among the groups demonstrating nephropathy and DKD (p=0.025 and 0.022 respectively. DFU was significantly associated with HTN (odds ratio 2.2; 95% CI 1.66 to 2.9; p &lt; 0.0001), nephropathy (odds ratio 4.77; 95% CI 3.53 to 6.5; p &lt; 0.0001) and DKD (odds ratio 4.77 and 6.83; 95% CI 4.6 to 10.2; p &lt; 0.0001). HbA1c of 7.8% was 60% sensitive and 52% specific for the development of DFU. Creatinine of 1.2 mg/dl was 75% sensitive and 48% specific for DFU. Spot urine protein excretion from nephrons of 35 mg/dl was 88% sensitive and 90% specific for the development of DFU. Conclusion: Nephropathy/DKD are risk factors for the development of DFU. With optimal diabetes control, regular and routine assessment of the feet and early screening of diabetic patients for neuropathy, nephropathy, hypertension, dyslipidaemia and other diabetic complications are essential. Doi: 10.28991/SciMedJ-2021-0304-6 Full Text: PDF