Nano-Oxy: Diabetic ulcer treatment using oxygen nanoparticles concept as innovation in reducing amputation rates and antibiotics usage

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by defects in insulin secretion, insulin reactions, or both. More than one third of diabetic patients have complications in the form of diabetic ulcers, and half are infected, and 15% of these infections require limb amputation. High cost expenditure and risks of microbial resistance to antibiotics also adds the complexity of the problem. The purpose of this literature review is to offer Nano-Oxy, using oxygen in nanoparticle size, as an alternative diabetic ulcer treatment. Literature searching was conducted through online search method. Oxygen therapy has been widely used to treat diabetic ulcers, including hyperbaric oxygen therapy (HOT) and topical oxygen therapy (TOT). Both of them have good results on diabetic ulcer therapy. Oxygen can act as an antimicrobial agent through the activation mechanism of neutrophils and macrophages which play a role in phagocytosis process and ROS regeneration. Nano-Oxy has advantages than the previous therapy, such as it does not cause barotrauma, oxygen poisoning, and low risk of burning. The mechanism of how Nano-Oxy works is similar with the Micro-nanobubbles (MNBs) concept. The negatively charged surface of MNBs can prevent them from aggregating, attracts particles, and help remove debris. MNBs also generate free radicals while shrinking in water, which contribute to its antibacterial effect. In addition, Nano-oxygen technology can be applied externally, but still have effect on the intended target cells. Therefore, Nano-oxygen can be used as a diabetic ulcer therapy to replace the role of antibiotics.

pH-switchable nanozyme cascade catalysis: a strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer

The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases. Graphical Abstract

KAJIAN LITERATUR: PERBANDINGAN EFEKTIVITAS TEKNIK WET TO DRY DRESSING DAN TEKNIK MOIST DRESSING PADA ULKUS DIABETIK [LITERATURE REVIEW: COMPARISON OF THE EFFECTIVENESS OF THE WET TO DRY DRESSING TECHNIQUE AND THE MOIST DRESSING TECHNIQUE IN DIABETIC ULCUS]

<p><em>Diabetes Mellitus is a metabolic disorder characterized by hyperglycemia. The most common complication of DM is diabetic neuropathy which causes an increase in further complications, including diabetic ulcers and often leads to amputation. In Indonesia, about 15% of DM patients have diabetic ulcers, 30% have a risk of amputation and 32% mortality. There are several types of wound care techniques, but the most used are the wet to dry and moist techniques. This study aims to compare the effectiveness of diabetic ulcer treatment with wet to dry and moist techniques. The research method used is thematic analysis: a simplified approach, by searching for articles using the Google Scholar database, EBSCO, Science Direct, JSTOR. The data selection process uses the PRISMA Flow Diagram and the JBI Critical Appraisal Checklist. The keywords used were "Wet to dry dressing AND moist dressing AND diabetic ulcer stage III", and "wet to dry dressing AND moist dressing AND grade III diabetic ulcer". The results showed that the moist wound dressing technique was more effective than wet to dry dressing in the treatment of diabetic ulcers, in terms of cost, dressing change, absorbency, basic ingredients and ingredients, pain caused and duration of wound healing. This study recommends that future researchers can conduct quantitative research on diabetic ulcer patients using both treatment techniques.</em></p><p><strong><em></em>BAHASA INDONESIA ABSTRAK: </strong>Diabetes Melitus merupakan gangguan metabolik dengan karakteristik hiperglikemia. Komplikasi DM paling umum adalah neuropati diabetik yang menyebabkan peningkatan komplikasi selanjutnya, diantaranya luka ulkus diabetik dan tidak jarang berlanjut pada amputasi. Di Indonesia sekitar 15% penderita DM mengalami ulkus diabetik, 30% memiliki risiko amputasi dan 32% mortalitas. Terdapat beberapa jenis teknik perawatan luka, namun yang paling sering digunakan adalah teknik <em>wet to dry</em> dan <em>moist</em>. Tujuan penelitian untuk membandingkan efektivitas perawatan luka ulkus diabetik dengan teknik <em>wet to dry</em> dan teknik <em>mois</em>t. Metode penelitian yang digunakan yaitu <em>thematic analysis: a simplified approach</em>, dengan pencarian artikel menggunakan database Google Scholar, EBSCO, Science Direct, JSTOR. Proses penyeleksian data menggunakan Flow Diagram PRISMA dan JBI <em>Critical Appraisal Checklist</em>. Kata kunci yang digunakan yaitu “<em>Wet to dry dressing AND moist dressing AND diabetic ulcer stage III</em>”, dan “balutan basah ke kering <em>AND</em> balutan lembab <em>AND</em> ulkus diabetik derajat III”. Hasil penelitian menunjukkan bahwa teknik <em>moist wound dressing</em> lebih efektif dari pada <em>wet to dry dressing</em> dalam perawatan luka ulkus diabetik, dilihat dari biaya, pergantian balutan, kemampuan menyerap, kandungan dan bahan dasar, nyeri yang ditimbulkan dan durasi penyembuhan luka. Penelitian ini merekomendasikan peneliti selanjutnya dapat melakukan penelitian kuantitatif pada pasien ulkus diabetik yang menggunakan kedua teknik perawatan.</p>

Glycemic Control and Diabetes Related Complications in Adults with Type 1 Diabetes Mellitus and ADHD

Objective: To assess the correlation of co-morbid ADHD and diabetes-related complications in patients with type-1-diabetes-mellitus (T1DM). Methods: A retrospective cross-sectional study was conducted during 2018 using the Leumit-Health-Services(LHS) database. Diabetes-related complications were assessed in patients with T1DM and ADHD (T1DM-ADHD+) and compared with patients with T1DM alone (T1DM-ADHD−). Results: Out of 789 adult-patients with T1DM, 75 (9.5%) were T1DM-ADHD+, matched to 225 T1DM-ADHD−. HbA1C levels were higher in T1DM-ADHD+ patients (8.1% ± 1.6 vs. 7.4% ± 1.2, p < .01), as well as diabetes-related complications: neuropathy (22.7% vs. 5.8%, p < .01), ulcers (8% vs. 0.9%, p < .05), limb amputation (5.3% vs. 0.9%, p < .05), albuminuria (15.5% vs. 2.8%, p < .01), chronic renal failure (10.6% vs. 2.5%, p = .01), and emergency room admissions rate (26.7% vs. 15.1%, p < .05). In sub-analysis, lower average HbA1C levels and diabetic ulcer rates were found among ADHD patients treated with stimulants, all p < .05. Conclusion: Co-morbidity of ADHD and T1DM is associated with poor glycemic control and higher complication rates.

Effectiveness of Self-Concept Management of Patients with Depression in Diabetic Ulcer Patients

Background: This study explores the management of self-concept in improving the quality of life of diabetic ulcer patients. Low confidence in the quality of life is a factor causing patients with long-term diabetic disease to believe they cannot be cured properly. Ulcers result from diabetes mellitus complications due to the nervous system and blood vessel damage. Patients with diabetic ulcers experience depression and feel acute stress when the disease has been categorized as a chronic condition. Method: This study uses quantitative methods with a cross-sectional study design approach. The data collection techniques used purposive sampling and had 82 diabetic ulcer sufferers as respondents in the study. Result: This study empirically proves that (p-value ≤ α=0.05), where there is effective management of the concept of self-health applied by diabetic ulcer patients in reducing the level of depression and sufferers can increase their confidence in better health factors. Conclusion: The effectiveness of self-care management is an important indicator in overcoming diabetic ulcer disease. The low management of self-concept for people with diabetes will certainly impact increasing depression and acute stress, decreasing the quality of life for sufferers.

The Effect Of Wound Care With Palm Sugar On Diabetic Ulcer Repairing In Type 2 Diabetes Patients

Diabetic ulcers are one of the most common complications of type 2 diabetes mellitus. Diabetic ulcers are infected sores that develop in the lower extremities. Proper diabetic foot wound care methods will improve wound healing. One of the efforts to treat the complement to prevent infection is wound care with palm sugar. Palm sugar contains antibiotic-like substances such as vitamin C, riboflavin, vitamin A, and ascorbic acid. Dr. Slamet Garut's study aims to determine the effectiveness of wound care with palm sugar media against the repair of diabetic ulcers in patients with type 2 diabetes mellitus after hospitalization in 2021. The study used a quasi experimental research design with one group pretest and posttest design (Pre-action) and one group of subjects receiving palm sugar therapy on diabetic ulcer wounds (Post-action). The researcher used consecutive sampling techniques, samples that met the inclusion criteria could have 8 people. The wounds were treated with palm sugar for two weeks. The findings revealed that wound care with palm sugar had an effect on the repair of diabetic ulcers in patients with type 2 diabetes mellitus, with a Pvalue = 0.000. Then it is possible to conclude that treating wounds with palm sugar affects the improvement of diabetic ulcers.

A Prospective Observational Study on Diabetic Induced Complications and their Prone towards Surgery

Background: This study was mainly aimed to find out the diabetic complications that had been lead to surgey. The Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate,fat and protein metabolism resulting from defects in insulin secretion,insulin action, or both.The effects of diabetes mellitus include long-term damage,dysfunction and failure of various organs. Materials and Methods: A prospective observational study was conducted in the Santhiram college & general hospital for 6 months (December 2020 – May 2021)to assess the macro vascular and micro vascular complications of diabetes mellitus and prone to surgery of diabetic complications by using case sheets, prescriptions in tertiary care teaching hospital. Results: A total of 150 patients are included in this study.In patients with diabetic complications we have observed: Diabetic ulcer with cellulitis in 19, gangrene in 19, peripheral vascular disease in 6, gangrene with cellulitis in 11,Non healing diabetes foot ulcer in 35, Coronary artery disease 24, diabetic retinopathy 25, MI in 11 patients.Among all complications, non healing diabetic foot was observed to be more when compared to other diabetic complications.In the study performed in diabetic induced complications of patients, debridement was performed in 30% patients, Amputation were performed in 13%, skin grating was performed in 13% patients, Angioplasty were performed in 23% patients and lasix surgery performed in 13% patients. Conclusion: In our study we conclude that out of 150 cases, male patients are more prone to diabetic complications than females.The patient counselling should involve in minimizing the incidence and prevalence of diabetes by conducting the continuing health education and other health programms.

Effectiveness of Infrared Radiation, in healing of diabetic ulcer foot at MAPIMS

Introduction: Diabetes is the non-communicable chronic health issue that affects people in the world wide. Studies shows that India is the second largest diabetes populated country in the world. Long standing uncontrolled diabetes leads to many systemic complications; diabetic ulcer foot is one among them that result in loss of foot or amputation and in severe cases even death. Objectives: this study investigated the pre and post test level would healing with infra-red radiation and also compared pre and post test mean score and found the demographic influences of the diabetic clients. Materials and methods: in a quantitative pre experimental one group pre-test post test design 75 diabetic ulcer foot clients who met the sampling criteria were included as sample. Consecutive sampling method was used to select the sample as they report to OPD or admitted as inpatient. Following pre-test Infra-red radiation was applied for 10 days and the post test was done seventh and tenth day. Result: The pre test mean and standard deviation were 51.5067 and 4.21828 respectively and the post test mean and standard deviation were 20.32 and 3.673 respectively. The” t” value was 68.352. Client’s demographic variables like education and occupation had significant influences in the wound healing process.

A prospective observation study on diabetic foot ulcer using diabetic ulcer severity score at tertiary care hospital

Background: A number of scoring systems and classifications are available for diabetic foot ulcers with intention to compare the treatment modalities and future outcomes. Many of them are complex and don’t predict future outcome within the patients. Aim and objectives of current study were to establish a wound-based clinical scoring systems (DUSS) as daily clinical practice by assessing the efficacy of diabetic ulcer severity score.Methods: A total of 73 diabetic patients with foot ulcers were included in this prospective observational study conducted at Dr. S.N. Medical college, Jodhpur and attached hospitals from July 2018 to August 2020. Ulcers were assessed and DUSS score created. Patients were followed up for six months or until healing or amputation if either.Results: In this prospective study of 73 patients with diabetic foot ulcers, most common age group affected was between 51-70 years. Mean age group was 58.57±12.66 years. Mean duration of diabetes was 7.61±5.72 years. Most commonly ulcers were of DUSS score 2. Mean DUSS score was 1.97±1.15. Majority of diabetic foot ulcer patients (37 out of 51) with DUSS score 0, 1 and 2 healed by primary intention after wound debridement. Those with score 3 & 4 majority of them (20 out of 22) had amputation.Conclusions: This is a very simple scoring system that provides an easily accessible and a streamlined approach in the clinical setting without need of any advanced investigative equipment. Hence this can be applied in any set up.