Ulcer Therapy Research Articles

Safe Use of Hyperbaric Oxygen Therapy in the Treatment of Diabetic Foot Ulcers: A Multidisciplinary Approach to Minimize Adverse Effects.

The purpose of this study is to evaluate the side effects associated with hyperbaric oxygen therapy and provide recommendations to prevent them in patients with diabetic foot ulcers. The use of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers remains a contentious issue, and minimizing side effects is critical. While the incidence of side effects related to hyperbaric oxygen (HBO2) therapy is low, it is essential to evaluate cases in a multifaceted and interdisciplinary manner to prevent adverse outcomes. A retrospective cohort study was conducted over the period of 2018-2020, involving a dataset of 100 patients. The primary objective of the study was to examine the frequency and types of side effects experienced by patients who underwent hyperbaric oxygen therapy (HBO) for diabetic foot ulcers (DFUs). In addition, we analyzed various wound characteristics, characteristics of hospitalizations, the surgical or medical interventions received by patients, and laboratory parameters including CRP levels, total blood count, culture results, HbA1c levels, duration of diabetes, treatment received for diabetes, and antibiotic therapy regimens. The percentage of patients who experienced side effects was as low as 6%, and none of them were critical. The most common side effect was discomfort due to the confined space in the chamber. Appropriate patient selection, combined with a multidisciplinary approach to evaluate eligibility, is crucial to avoid adverse side effects. Patient education and early screening for side effects are also essential. Since various treatment protocols exist for HBO2 therapy, pooled data from different protocols may be misleading. Further studies focused on side effects with specific indications are necessary.

Efficacy of microcurrent therapy versus laser therapy for diabetic foot ulcer on size of the wound

Efficacy of microcurrent therapy versus laser therapy for diabetic foot ulcer on size of the wound

Formulation and Evaluation of Prednisolone Sodium Metazoate-Loaded Mucoadhesive Quatsomal Gel for Local Treatment of Recurrent Aphthous Ulcers: Optimization, In Vitro, Ex Vivo, and In Vivo Studies.

This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 23 factorial design was conducted to address the impact of independent variables QAS type (X1), QAS to CHO molar ratio (X2), and sonication time (X3). The dependent variables were particle size (PS; Y1), polydispersity index (PDI; Y2), zeta potential (ZP; Y3), entrapment efficiency percent (EE%; Y4) and percent of drug released after 6 h (Q6%: Y5). Then, the selected quatsomes formula was incorporated into different gel bases to prepare an optimized mucoadhesive gel to be evaluated via in vivo study. The PS of the developed quatsomes ranged from 69.47 ± 0.41 to 113.28 ± 0.79 nm, the PDI from 0.207 ± 0.004 to 0.328 ± 0.004, ZP from 45.15 ± 0.19 to 68.1 ± 0.54 mV, EE% from 79.62 ± 1.44 to 98.60% ± 1.22 and Q6% from 58.39 ± 1.75 to 94.42% ± 2.15. The quatsomal mucoadhesive gel showed rapid recovery of ulcers, which was confirmed by the histological study and the evaluation of inflammatory biomarkers. These results assured the capability of the developed quatsomal mucoadhesive gel to be a promising formulation for treating buccal diseases.

Evaluation of the effect of umbilical cord blood serum therapy in resistant infected corneal ulcer

Background Corneal wound healing involves several complex pathways that can be targeted by drugs with varying mechanisms of action. Infected corneal ulcers represent a special challenging situation facing ophthalmologists due to resistance to treatment and visual impairing complications. Purpose The aim of this study was to evaluate the efficacy of umbilical cord blood serum (CBS) as an adjunctive therapy for resistant infected corneal ulcers. Patients and methods This prospective cohort study included 40 eyes having infected corneal ulcer resistant to specific medical treatment for 2 weeks. The patients were recruited from the Cornea Unit at Tanta University Hospital, Tanta, Egypt. They were divided into two groups, 20 cases each. Group A cases were treated with umbilical CBS as an adjunctive therapy together with medical treatment based on culture and sensitivity testing, while group B cases continued the conventional medical treatment only till the complete healing was achieved. The results of the two groups were compared regarding the duration of healing and best-corrected visual acuity improvement. Results Visual acuity improvement was achieved with one or more line gain in 14 (70%) cases in group A compared to 6 (30%) cases in group B, with a statistically significant difference (P = 0.008). Healing was achieved in 16 (80%) cases of group A in 2–4 weeks compared to 14 (70%) cases of group B that achieved healing in a longer duration of 3–6 weeks, with a statistically significant difference (P = 0.001). Amniotic membrane transplantation AMT was required in 4 (20%) cases in group A due to thinning compared to 6 (30%) cases in group B. Conclusion Umbilical CBS was safe and effective when applied to the cornea as an adjunctive therapy in cases of resistant infected corneal ulcers where it accelerated healing with better visual outcome results.

Study of the antiulcer activity of garden cabbage extract on the chronic acetic ulcer model in rats

The aim of the study was to study the gastroprotective properties of the dry extract of garden cabbage in the model of chronic acetic ulcer in rats.
 Materials and methods. Chronic ulcerative lesions of the gastric mucosa of rats were modeled by introducing 0.05 ml of a 30 % solution of acetic acid into the subserous layer of the stomach wall. The dry extract of garden cabbage in a conditionally therapeutic dose of 50 mg/kg and reference drugs omeprazole and altan were administered intragastrically for 10 days, starting from the second day of the experiment. When choosing the duration of the course of treatment, we proceeded from the data that the effectiveness of the antiulcer action in the clinic is assessed after 10-12 days of treatment. The percentage of animals with ulcers in the group, the state of the gastric mucosa were evaluated, the ulcer index and antiulcer activity were calculated. To elucidate the possible mechanism of action of the extract, we studied its effect on synthetic processes in terms of the content of RNA and DNA in homogenates of the gastric mucosa by the spectrophotometric method by reaction with perchloric acid.
 Results. On the model of stomach damage, caused by acetic acid, a pronounced antiulcer activity of the extract (54.26) was established at the level of omeprazole (54.62). The maximum antiulcer activity (72.75) was revealed when using the combination of the extract with omeprazole, which, in terms of ulcerative effect, is superior to monotherapy with the extract, omeprazole and altan (35.08).
 Reparative regeneration is a component of an adaptive tissue reaction; under conditions of violation of the reparative potencies of the mucosa, chronic diseases of the gastrointestinal tract develop. Since the final goal of antiulcer therapy is the healing of the ulcer, and the basis of this process is reparative regeneration, the reparative properties of the extract have been studied. Under the influence of cabbage extract, the content of RNA and DNA in the mucosa probably increased by 2.8 and 2.4 times, respectively, at the same level with omeprazole. If possible, to activate the synthetic processes of DEGC and omeprazole, altan significantly prevailed.
 The most pronounced effect of enhancing reparative processes was established with the combined use of the extract and omeprazole, which turned out to be a significant increase in the content of RNA and DNA in the gastric mucosa by 3.2 and 2.9 times compared with the control.
 Conclusions. On the model of chronic damage to the stomach of rats, cabbage extract showed an antiulcer effect, the severity of which was not inferior to the comparison drug, the proton pump inhibitor omeprazole, and significantly exceeded the phytopreparation - altan. The combined use of the extract and omeprazole showed the highest preventive effect of preventing the negative effects of acetic acid on the gastric mucosa. One of the mechanisms of the gastroprotective action of the extract is its ability to enhance reparative processes in the gastric mucosa. The results obtained indicate the prospects for further research on the antiulcer properties of cabbage extract with a view to its use in the complex therapy of peptic ulcer

Optimal Diagnosis and Therapy of Venous Ulcer

Optimal Diagnosis and Therapy of Venous Ulcer

A Prospective Observational Multi-Centre Study on the Use of Negative Pressure Wound Therapy in Diabetic Foot Ulcer

This implies that larger wound size with the help of adjunctive method after NPWT application enhances wound healing in DFU.

Ulcerous disease in nurse practice

This article is a literary review, highlights issues related to the etiology, classification, pathogenesis, clinical symptoms, approaches to the diagnosis and effective complex therapy of peptic ulcer of the duodenum. However, the pylori tag plays an important role in the pathogenesis of YAB. Currently, the arsenal of eradication protocols is quite extensive. The choice of the eradication treatment option should take into account the population antibiotic resistance and the individual history of antibiotic use. According to research, the use of the first line of quadrotherapy is considered the most effective.

Comparative efficacy of growth factor therapy in healing diabetes-related foot ulcers: A network meta-analysis of randomized controlled trials.

This study examined the relative efficacy of growth factor therapies in healing diabetes-related foot ulcers (DFU). PubMed and Cochrane databases were searched for randomized controlled trials testing growth factor therapies for treating DFU. The primary outcome was complete wound closure. Results were reported as relative risk (RR)±95% credible intervals (CrI). The risk of bias was assessed using Cochrane's RoB-2 tool. A total of 31 RCTs involving 2174 participants were included. Only 13 of the trials (n=924) reported on the aetiology of the ulcers (85.4% neuropathic and 14.6% ischaemic). Epidermal growth factor (RR 3.83; 95% CrI 1.81, 9.10), plasma-rich protein (PRP) (RR 3.36; 95% CrI 1.66, 8.03) and platelet-derived growth factor (PDGF) (RR 2.47; 95% CrI 1.23, 5.17) significantly improved the likelihood of complete ulcer healing compared to control. Sub-analyses suggested that PRP (3 trials - RR 9.69; 95% CrI 1.37, 103.37) and PDGF (6 trials - RR 2.22; 95% CrI 1.12, 5.19) significantly improved the likelihood of wound closure amongst trial mainly recruiting participants with neuropathic ulcers. Eleven trials had a low risk of bias, 9 had some concerns and 11 had a high risk of bias. Sub-analysis of trials with a low risk of bias suggested that none of the growth factors significantly improved ulcer healing compared with control. This network meta-analysis found low-quality evidence that Epidermal growth factor, PRP and PDGF therapy improved DFU healing likelihood compared with control. Larger well-designed trials are needed.

Gene therapy for diabetic foot ulcers: Interim analysis of a randomised, placebo-controlled phase 3 study of VM202 (ENGENSIS), a plasmid DNA expressing two isoforms of human hepatocyte growth factor.

To evaluate the status of a 7-month phase 3 study conducted to test the effect of intramuscular injections of VM202 (ENGENSIS), a plasmid DNA encoding human hepatocyte growth factor, into the calf muscles of chronic nonhealing diabetic foot ulcers with concomitant peripheral artery disease. The phase 3 study, originally aimed to recruit 300 subjects, was discontinued because of slow patient recruitment. An unprespecified interim analysis was performed for the 44 subjects enrolled to assess the status and determine the future direction. Statistical analyses were carried out for the Intent-to-Treat (ITT) population and separately for subjects with neuroischemic ulcers, using a t-test and Fisher's exact test. A logistic regression analysis was also conducted. VM202 was safe and potentially should have benefits. In the ITT population (N = 44), there was a positive trend toward closure in the VM202 group from 3 to 6 months but with no statistical significance. Levels of ulcer volume or area were found to be highly skewed between the placebo and VM202 groups. Forty subjects, excluding four outliers in both arms, showed significant wound-closing effects at month 6 (P = .0457). In 23 patients with neuroischemic ulcers, the percentage of subjects reaching complete ulcer closure was significantly higher in the VM202 group at months 3, 4, and 5 (P = .0391, .0391, and .0361). When two outliers were excluded, a significant difference was evident in months 3, 4, 5, and 6 (P = .03 for all points). A potentially clinically meaningful 0.15 increase in Ankle-Brachial Index was observed in the VM202 group at day 210 in the ITT population (P = .0776). Intramuscular injections of VM202 plasmid DNA to calf muscle may have promise in the treatment of chronic neuroischemic diabetic foot ulcers (DFUs). Given the safety profile and potential healing effects, continuing a larger DFU study is warranted with modifications of the current protocol and expansion of enrolling sites.

Experience in complex therapy of lower limb trophic ulcers of venous and diabetic origin

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.

Diverse Antibacterial Treatments beyond Antibiotics for Diabetic Foot Ulcer Therapy.

Diabetic foot ulcer (DFU), a common complication of diabetes, has become a great burden to both patients and the society. The delayed wound closure of ulcer sites resulting from vascular damage and neutrophil dysfunction facilitates bacterial infection. Once drug resistance occurs or bacterial biofilm is formed, conventional therapy tends to fail and amputation is unavoidable. Therefore, effective antibacterial treatment beyond antibiotics is of utmost importance to accelerate the wound healing process and prevent amputation. Considering the complexity of multidrug resistance, biofilm formation, and special microenvironments (such as hyperglycemia, hypoxia, and abnormal pH value) at the infected site of DFU, several antibacterial agents and different mechanisms have been explored to achieve the desired outcome. The present review focuses on the recent progress of antibacterial treatments, including metal-based medications, natural and synthesized antimicrobial peptides, antibacterial polymers, and sensitizer-based therapy. This review provides a valuable reference for the innovation of antibacterial material design for DFU therapy.

An In-Vivo Study of Effects of Platelet-Rich Plasma on Transforming Growth Factor-β1 and Matrix Metalloprotein 9 Expression in Traumatic Ulcers with Diabetes Mellitus.

Diabetes mellitus is not only characterized by alterations in the wound healing process but also during oral ulcer healing. The platelet-rich plasma (PRP) can be used to stimulate the healing process. This study was performed to analyze the effect of PRP on traumatic ulcers with diabetes mellitus in an animal model by analyzing the expression of transforming growth factor β1 (TGF-β1) and matrix metalloprotein 9 (MMP-9). The diabetes mellitus model was developed using streptozotocin that was administrated to Rattus novergicus. The traumatic ulcer model was obtained by placing a heated tip of a ball burnisher for 5 seconds on the lower mucosa labial. Then, the traumatic ulcer was treated with PRP for 3, 5, and 7 days. The expression of TGF-β1 and MMP-9 was analyzed with indirect immunohistochemistry, and differences between each marker were analyzed with statistical analysis. All animals showed clinical oral ulceration as a yellow base during the experiment. The application of PRP showed a higher level of TGF-β1 expression than the controls for 3, 5, and 7 days (p < 0.05). In contrast, the MMP-9 expression was lower than the control for 5 and 7 days (p < 0.05). The PRP affected traumatic ulcers with diabetes mellitus by promoting healing through TGF-β1 expression and suppressing the MMP-9 expression. This material can serve to develop a promising topical therapy for traumatic ulcers, especially with an underlying disease such as diabetes mellitus.

A novel method to pack cryopreserved amniotic membrane for wound dressing—the pathway through validation of a new biological product

Amniotic membrane (AM) has been widely used as a biological dressing for many pathologies and illnesses worldwide, and products derived from this tissue have been commercially available in several countries. In Brazil, regulatory agencies have recently authorized its clinical use as a non-experimental therapy for burns, diabetic and venous stasis ulcers, and intrauterine adhesions. In this study, we present our pathway through validating the first available service in the country of AM cryopreservation, with a protocol for long-term storage in high-efficiency nitrogen cryogenic freezers and a specific way of packing the tissue for optimal clinical handling and efficient storage space utilization while preserving live cells and the tissue’s biological properties. Using gauze as support, cryoprotectant dimethyl sulfoxide and product presentation as a multilayer roll exhibited the best cell viability results and maintained the tissue integrity and presence of stem/progenitor cells. Essential proteins involved in tissue regeneration and immune and antimicrobial control were detected from the secretome of cryopreserved tissue similar to fresh tissue. Furthermore, immunogenic markers, such as human leukocyte antigens, were detected at very low levels in the tissue, confirming their low immunogenicity. Finally, we demonstrate that the tissue can be kept under refrigerated conditions for up to 7 d for further use, maintaining sterility and considerable cell viability. Our cryopreservation and storage protocol kept the AM viable for at least 20 months. In conclusion, this study enabled us to determine a novel efficient protocol for long-term AM preservation for future clinical applications.

A remote fluorescein staining and photography protocol for monitoring of ulcerative keratitis in small animal patients: A pilot study.

To describe a protocol for corneal ulcer monitoring utilizing daily fluorescein staining and evaluation of owner-acquired anterior segment images. Nine client-owned small animal patients (eight dogs, one cat) diagnosed with superficial corneal ulcers at the University of Georgia Veterinary Capitalize Hospital. In addition to routine ulcer therapy, patients were discharged with supplies to perform daily fluorescein staining including a Quikvue® cobalt blue light camera adapter. Fluorescein staining was performed daily, photographs and/or videos were acquired at home by the patient's owner(s), and images were analyzed daily by trained personnel. In-house examinations were performed weekly and within 24 h after the ulcer had appeared healed on photographs. All (9/9) owners were able to take interpretable photographs. The majority (6/9) of patients had images successfully detailing their ulcer healing progress. One (1/9) patient appeared healed on images, but on subsequent examination had persistent ulceration covered by third eyelid elevation. Two (2/9) patients had persistent ulceration, consistent on both images and examination, but exited the study prematurely prior to ulcer healing. Remote fluorescein staining and image evaluation can be considered as an adjunct for monitoring ulcer healing but should not be used alone or as a substitute for ophthalmic examinations. Ulcers under the third eyelid have potential to be missed on image evaluation alone.

Use of hyperoxidized oils-based medical devices for the wound healing in post-surgical patients.

Postoperative injuries of the lower limb represent a challenging complication after surgery. The use of advanced dressings, local flaps, reconstructions with grafts or dermal substitutes represent the most common therapeutic solutions. With the present paper, we describe a case of a postoperative wound of the leg treated with the use of hyperoxidized oils-based medical device: NOVOX©. An 88-year-old woman presented in September 2022 an ulcer on her left leg, on the external malleolus. Authors decided to treat the lesion with NOVOX© in the form of a dressing pad. The controls initially lasted every 48 hours, subsequently every 72 hours and in the last month only once a week. The progressive clinical examination showed a global reduction of the wound area. According to our experience, the novel oxygen-enriched oil-based dressing pad (NOVOX©) is simple to use, secure, and successful in treating old patients receiving postoperative therapy for leg ulcers.

Physical therapy in diabetic foot ulcer: Research progress and clinical application.

Diabetes foot ulcer (DFU) is one of the most intractable complications of diabetes and is related to a number of risk factors. DFU therapy is difficult and involves long-term interdisciplinary collaboration, causing patients physical and emotional pain and increasing medical costs. With a rising number of diabetes patients, it is vital to figure out the causes and treatment techniques of DFU in a precise and complete manner, which will assist alleviate patients' suffering and decrease excessive medical expenditure. Here, we summarised the characteristics and progress of the physical therapy methods for the DFU, emphasised the important role of appropriate exercise and nutritional supplementation in the treatment of DFU, and discussed the application prospects of non-traditional physical therapy such as electrical stimulation (ES), and photobiomodulation therapy (PBMT) in the treatment of DFU based on clinical experimental records in ClinicalTrials.gov.

Bacteriophage therapy in diabetic foot ulcer caused by Pseudomonas aeruginosa.

Bacteriophage therapy in diabetic foot ulcer caused by Pseudomonas aeruginosa.

Venous ulcers: look at the patient, not at the ulcer! Risk factors and comorbid conditions in venous ulcers of lower limbs.

In venous leg ulcers (VLU), risk factors and comorbidities may affect prognosis and recurrence. Aim of this paper was to assess risk factors and most frequent medical conditions in venous ulcers. This a single center retrospective study from January 2017 to December 2020 on 172 patients with VLU admitted at our Center for Ulcer therapy in San Filippo Neri Hospital in Rome; data about medical history, Duplex scanning results and lifestyle questionnaire were collected in an Excel database and evaluated with Fisher test. Patients with lower limbs arterial insufficiency were excluded. Incidence of VLU in patients over 65 was twice that in patients under 65 and woman were affected by VLU more than men (59.3% vs. 40.7%; P<0.001); more significant comorbidities were arterial hypertension in 44.19% (P=0.06), heart disease in 35.47% (P<0.001), chronic obstructive pulmonary disease (COPD) in 16.28% (P=0.008). In 33 patients (19% of cases) a trauma caused the ulcer. Diabetes, obesity, chronic renal insufficiency and orthopedic disease do not seem to have a direct influence on VLU. Age, female sex, arterial hypertension, heart disease and COPD were significant risk factors. Thinking "globally" to the patient rather than only taking the ulcer into account is the key for a long-lasting therapeutic result; comorbidities are interconnected so weight loss, an exercise program for calf pump and compression must all be part of the VLU therapy, not only to heal the existing ulcer but also to prevent recurrences.

Retrospective Study of Decubitus Ulcer in Hospitalized Patients

Background: Decubitus ulcer is an area of necrotic tissue due to compression of protrusion because of prolonged immobilization. Decubitus ulcer is complication that often occur due to prolonged bed rest. Decubitus ulcer can interfere with patient’s recovery process and prolonged hospital stay. Purpose: To investigate profile of decubitus ulcer in hospitalized patients in Dr. Moewardi General Hospital Surakarta during 2017- 2020. Methods: This descriptive retrospective study was conducted by using medical record of decubitus ulcers (ICD 10 L89.0, L89.1, L89.2, L89.3) in Dr. Moewardi General Hospital Surakarta during 1st January 2017-31st December 2020. Result: There were 375 decubitus ulcer patients, mostly aged 70 years or more (29.1%) and dominated by women (56%). Patients with decubitus ulcers often hospitalized in the regular ward (75.2%) with the longest length of stay being around 0-10 days (49.6%) and the most common comorbidities was malignancy (20.5%). Systemic antibiotic ceftriaxone was most often given to decubitus ulcer patients (21.6%). Most of the patients with decubitus ulcers had stage 2 decubitus ulcers (53.6%) with a predisposition to the affected area being the sacrum area (33%). The most frequently used therapy for decubitus ulcers was hydrogel dressing (33.9%). Conclusion: Decubitus ulcers are often found in patients over 70 years of age with comorbid malignancies. The most common diagnosis was stage 2 decubitus ulcers, predisposing to the sacral region and the most frequently used therapy was hydrogel dressing with ceftriaxone as a systemic antibiotic.