EFFICACY OF NEGATIVE PRESSURE WOUND THERAPY IN EARLY DIABETIC FOOT ULCER MANAGEMENT IN COMPARISON WITH ADVANCED MOIST WOUND THERAPY

Objective: To compare negative pressure wound therapy with advanced moist wound therapy in managing early diabetic foot ulcer. Study Design: Quasi-experimental study. Place and Duration of Study: Surgical Department, Combined Military Hospital Rawalpindi, from Jul 2016 to Jun 2018. Methodology: A total of 100 patients of diabetic foot ulcer were randomly allocated into two equal groups for the treatment with negative pressure wound therapy (NPWT) and advanced moist wound therapy (AMWT). Ulcers were reassessed after 4 weeks for presence of granulation tissue covering entire ulcer base and reduction of 3 cm in largest diameter of ulcer. Results: Mean age of the study participants was 57.08 ± 9.99 years. 33 patients had Wagner grade-I ulcer, while remaining had Wagner grade-II ulcer. Mean ulcer size at presentation was 6.46 ± 1.71 cm. Both study groups were comparable in terms of mean age (p=0.968), wound size at presentation (p=1.000), age (p=0.695), gender (p=1.000) and Wagner ulcer grade (p=0.288). Mean ulcer size was found smaller with negative pressure wound therapy (3.46cm, p=0.061) at follow-up visits. Reduction in ulcer size ≥3cm was achieved frequently with negative pressure wound therapy technique (72.0% vs. 38.0%; p>0.01). Mean healing time was 4.11 ± 1.65 weeks which was lower with negative pressure wound therapy (3.66 weeks vs. 4.56 weeks; p>0.05). Treatment efficacy (healing in ≤4 weeks and ≥3cm reduction in ulcer) was significantly higher with negative pressurewound therapy (72.0% vs. 38.0%; p<0.01) as well. Conclusion: This study demonstrates superiority of negative pressure wound therapy over advanced moist...............

CLINICAL EFFICACY AND SAFETY OF HERBAL MEDICINE THERAPY IN RECURRENT APHTHOUS STOMATITIS: A SYSTEMATIC REVIEW

Recurrent aphthous stomatitis is the most common oral mucous ulcerative lesion with challenging treatment. Herbal medicine therapy can propose clinical efficacy and safety due to its large biological activities. The objective was to review the clinical efficacy and safety of herbal medicine therapy in terms of ulcer size, pain score, healing duration, and adverse effects in recurrent aphthous stomatitis. A systematic was conducted based on the PRISMA statement. The search was performed using four electronic databases, namely PubMed, Cochrane, Science Direct, and Google Scholar for articles published from 2016 until 2021 using specific keywords. The search was limited to randomized controlled trials (RCTs), in English, full text, and study in humans. The main outcome is expected to be ulcer size, pain score, healing duration, and adverse effects. Quality assessment of selected articles was conducted using the Quality Appraisal of Randomized Trials Checklist (Cochrane Risk of Bias tool). The methodology quality of studies was evaluated using the Cochrane Handbook for Systematic Review of Interventions and Rev Man software. Five articles were eligible for analysis. The population of the sample study ranged from 34-70 patients of 15-65 y old. The herbs used were Aloe vera (Aloe barbadensis Miller), curcumin (Curcuma longa), licorice (Glycyrrhiza glabra), tobacco (Nicotiana tabacum L.), and pomegranate (Punica granatum Linn.). This review showed that there is some evidence of the clinical efficacy and safety of herbal medicine therapy in improved outcomes of recurrent aphthous stomatitis treatment with minimum adverse effects.

Efficacy and Safety of Pentoxifylline for Venous Leg Ulcers: An Updated Meta-Analysis

The venous leg ulcers are debilitating, painful, and often unresponsive to advanced dressing treatments, so drugs used locally and systematically are essential adjuvant therapy—pentoxifylline (PTX) whose anti-inflammatory effects may offer a promising avenue to treat venous leg ulcers. However, the current results are controversial. To further evaluate the efficacy and safety of PTX, we performed an updated meta-analysis of randomized placebo-controlled trials of PTX in the treatment of venous leg ulcers. We systematically searched multiple electronic databases PubMed, Web of Science, Embase, the Cochrane Library, the Cochrane Central Register of Controlled Trials, China Science and Technology Journal Database, WanFang Data, China National Knowledge Infrastructure, and the Chinese Biomedical Literature Database to identify eligible studies. Randomized clinical trials of pentoxifylline versus placebo treatment in patients with venous leg ulcers were considered for inclusion. The primary outcomes included ulcer healing rate and the incidence of adverse events after treatment. The secondary outcomes were the ulcer significant improvement (the ulcer size shrank by more than 60% after treatment) rate, mean duration of complete wound healing and changes in mean ulcer size. A meta-analysis and qualitative analysis were conducted to estimate endpoints. A total of 13 randomized clinical trials, including 921 individuals, were finally included. Compared with placebo, pentoxifylline significantly improved the ulcer healing rate (RR = 1.59, 95%CI 1.22 to 2.07, P < .001) and significant improvement rate (RR = 2.36, 95%CI 1.31 to 4.24, P = .004) while increased the incidence of gastrointestinal disturbances (RR = 2.29, 95%CI 1.04 to 5.03, P = .04) at the same time. Moreover, pentoxifylline also shortened mean duration of complete wound healing ( P = .007) and shrank ulcer size ( P = .02). Currently available evidence suggests that pentoxifylline could help venous leg ulcers heal more quickly and effectively. However, the evidence is insufficient to prove the results due to moderate-certainty evidence. Large-scale, well-designed randomized clinical trials are warranted.

Evaluation of Therapeutic Efficacy of Stigma and Petal Extracts of Crocus sativus L. on Acetic Acid-Induced Gastric Ulcer in Rats

Saffron (Crocus sativus L.) has long been considered a medicinal plant in Traditional Persian Medicine (TPM) due to its therapeutic properties. Despite this interest, its effects on gastrointestinal disorders have not been completely taken into consideration. Hence, this study aimed to evaluate the pharmacological activity of ethanolic extracts of saffron stigma (SS) and saffron petal (SP) in acetic acid-induced gastric ulcer in rats. The gastric ulcer model was imitated by the serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed with 100 mg/kg and 200 mg/kg of ethanolic extracts of SS or SP, omeprazole (40 mg/kg), or saline for 12 days. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. The highest anti-ulcer activity was observed in the omeprazole-treated animals with the lowest ulcer size (4.29 ± 1.78 mm2). SS could not reduce gastric ulcer size in rats. Compared to the untreated rats, SP treatment significantly decreased ulcer indices in a dose-dependent manner. The gastric levels of PGE2, VEGF, and MDA were significantly elevated in the untreated animals with gastric ulcers compared to rats in the control group. The SS extract suppressed the elevated PGE2 and VEGF levels at both doses, while SP did not have a significant influence. Both SS and SP treatments significantly ameliorated MDA levels in rats with gastric ulcers. Omeprazole treatment enhanced the PGE2 level and suppressed MDA contents, but it did not influence the VEGF level. In conclusion, our findings demonstrated that the saffron stigma has no significant effects on the gastric ulcer healing process, while its petals accelerate the process. This discrepancy can be attributed to the difference in the main secondary metabolites between saffron stigma and petals.

Prognostication of Asymptomatic Penetrating Aortic Ulcers: A Modern Approach

Background: Literature detailing the natural history of asymptomatic penetrating aortic ulcers (PAU) is sparse and lacks long-term follow-up. This study sought to determine the rate of asymptomatic PAU growth over time and adverse events from asymptomatic PAU. Methods: A cohort of patients with asymptomatic PAU from 2005-2020 was followed. One ulcer was followed per patient. Primary endpoints were change in size over time and the composite of symptoms, radiographic progression, rupture, and intervention; cumulative incidence function estimated the incidence of the composite outcome. Ulcer size and rate of change were modeled using a linear mixed effects model. Patient and anatomic factors were evaluated as potential predictors of the outcomes. Results: There were 273 patients identified. Mean age was 75.5±9.6 years; 66.4% were male. The majority of ulcers were in the descending thoracic aorta (53.9%), followed by abdominal aorta (41.4%), and aortic arch (4.8%). Fusiform aneurysmal disease was present in 21.6% of patients at a separate location; 2.6% had an associated intramural hematoma; 23.6% had at least one other PAU. Symptoms developed in one patient who ruptured; 8 patients (2.9%) underwent an intervention for PAU (one for rupture, 2 for radiographic progression, 5 for size/growth) at a median of 3.1 years (IQR:1.0-6.5) after diagnosis. Five and 10-year cumulative incidence of the primary outcome, adjusted for competing risk of death, was 3.6% (95% CI: 1.6-6.9%) and 6.5% (95% CI: 3.1-11.4%), respectively. For 191 patients with multiple CT scans (760 total CT's) with median radiographic follow-up of 3.50 years (IQR:1.20-6.63 years), mean initial ulcer width, ulcer depth, and total diameter in millimeters (mm) was 13.6, 8.5, and 31.4, respectively. Small, but statistically significant change over time was observed for ulcer width (0.23 mm/year) and total diameter (0.24 mm/year); ulcer depth did not significantly change over time. Hypertension, hyperlipidemia, diabetes, initial ulcer width>20 mm, thrombosed PAU, and associated saccular aneurysm were associated with larger changes in ulcer size over time, however the magnitude of difference was small, ranging from 0.4-1.9 mm/year. Conclusions: Asymptomatic PAU displayed minimal growth and infrequent complications including rupture. Asymptomatic PAU may be conservatively managed with serial imaging and risk-factor modification.

A COMPARATIVE STUDY BETWEEN THE EFFECTIVENESS OF AUTOLOGOUS PLATELET-RICH FIBRIN VERSUS SALINE DRESSING IN THE MANAGEMENT OF CHRONIC VENOUS LEG ULCERS

Background: Venous disease is responsible for around 85% of all chronic lower limb ulcers in resource-rich countries. Venous leg ulcer is a chronic condition, and various treatment modalities are available. Various adjunctive wound care therapies and procedures are available that can be utilized as part of a comprehensive approach to healing venous stasis ulcers. Platelet-rich brin (PRF) is one of the newer modalities and it contains broblast growth factor (FGF), VEGF, angiopoietin and platelet-derived GF which enhances the wound healing. We conducted a randomized controlled trial to compare the efcacy of PRF versus saline dressing in chronic venous leg ulcers. Aim: To compare the efcacy of autologous PRF with saline dressing in patients with chronic venous leg ulcer in terms of mean reduction in ulcer area, presence of infection and cosmetic outcome at the end of 4 weeks. Materials and Methods: Thirty patients with chronic venous leg ulcers of >6 months duration having an ulcer area of 1 cm × 1 cm to 5 cm × 5 cm were taken into the study and were randomly divided into two groups. Group 1: Patients received PRF dressing. 10 mL of patient's blood was taken and centrifuged at 3000 rpm for 15 min. A brin clot obtained in the middle of the tube was removed and used for dressing over the wound surface. It was repeated every week for 4 weeks. Group 2: Patients received saline dressings once a week for 4 weeks. The assessment of the ulcer size was done with the help of photographs, and ulcer area was measured. Results: The mean reduction in the area of the ulcer size in PRF group was 81.84%, and the mean reduction in the area of the ulcer size in Saline group was 59.84%. Conclusion: Platelet rich brin matrix is a novel modality and an ideal, safe, affordable therapeutic option for chronic venous leg ulcers.

Efficacy of 5% Tea Tree Oil Hydrogel on Healing Morbus Hansen's Chronic Plantar Ulcer

Background: The damage of the peripheral nerves that occurs in Morbus Hansen (MH) patients can cause disability due to loss of sensory, motor and autonomic functions can cause wounds, infections, ulcers and disability. Ulcers are the most common cause of disability complications in MH patients and requires a certain time of healing. As many as 10-20% of MH patients experience ulcers on the soles. Tea Tree Oil (TTO) is extracted from steam distillation of the leaves and twigs of the Australian native shrub Melaleuca Alternifolia. In ulcers, TTO can work as an antimicrobial, anti-inflammatory, and antioxidant. TTO preparation in the form of hydrogel is believed to help the wound healing process. Purpose: To investigate the effect of TTO hydrogel 5% on the healing of Chronic Plantar Ulcer of Leprosy (CPUL). Methods: Tea tree oil hydrogel 5% was applied every 3 days for up to 8 weeks in 22 subjects with chronic MH plantar ulcers. Ulcer size, side effects, and possible side effects are evaluated weekly. Result: There were significant clinical and statistical differences in ulcer size (p = 0.000) and in ulcer depth (p = 0.000) after TTO hydrogel 5%. No side effects occurred in this study. The ulcer healed was 59%, the ulcer improved by 36.4%, the persistent ulcer was 4.6%, and there was no ulcer that got worse. Conclusion: TTO hydrogel 5% is effective in the healing process of chronic MH plantar pedis ulcers.

Comparison of Virgin Coconut Oil with 5% Amlexanox in Management of Minor Recurrent Aphthous Ulcers - A Randomized Control Trial

Objective: Recurrent Aphthous Ulcer (RAU) is a common (75-80%) painful inflammatory ulcerative disorder of the non-keratinized oral mucosa. Wide range of antiseptics, anti-inflammatory, antibiotics and corticosteroids are available for treatment. Amlexanox is a topical anti-inflammatory and anti-allergic drug used to treat RAS. Recently, there has been increase in interest in use of essential oil and herbal medicine in managing RAU, one such natural product is virgin coconut oil. This study is aimed to determine the efficacy of VCO in management of signs and symptoms of minor recurrent aphthous ulcers. Methodology: 40 patients were included for the study who were randomly divided into two groups. 20 patients in Group A (VCO) and 20 patients in Group B (5%Amlexanox). Primary outcome measured were reduction in ulcer size (in mm) and pain (VAS 1-10). Results: There is high statistical significant difference within the groups in ulcer healing and pain reduction (p=0.00) on 3rd and 5th day. In group A significant reduction in pain was present on the 5th day (p=0.02) and no significant reduction in ulcer size (p=0.083). No adverse effects were reported in either group. Conclusion: VCO could be used as an effective and safe drug in managing the signs and symptoms of RAS. It is edible oil with no known adverse effects and could be a safe therapeutic alternative in children and pregnant women.

Morphine Versus Loperamide with Intrasite Gel in the Treatment of Painful Dermal Ulcers: A Randomized, Crossover Study

BACKGROUND: Topical morphine along with intrasite gel has been proven to be a simple and effective method to relieve pain. However, morphine is still not freely available in developing countries due to drug restrictions and stringent laws governing it. Loperamide has been reported to relieve pain caused by stomatitis effectively when given topically. Loperamide, being an mu receptor agonist with no systemic absorption, can serve a dual purpose here. Also loperamide being freely available as an over-the-counter drug can be a surrogate drug for topical application. OBJECTIVES: The primary aim was to compare the efficacy of loperamide and morphine in treating pain when applied topically along with intrasite gel. STUDY DESIGN: Adult patients with healthy wounds with pain on Numeric Rating Scale (NRS-11) greater than 5 with no systemic comorbid illness were divided randomly into 2 groups – group morphine or group loperamide – for 24 hours followed by a 1-day washout and crossover in the other group for 24 hours. Pain was assessed once every day. SETTING: Medical college and hospital. METHODS: The parameters assessed included: (1) characteristics of the ulcer; (2) pain was assessed by NRS-11 at 12-hour intervals for a period of 72 hours; and (3) patient satisfaction. Statistical analysis used repeated measures analysis of variance to measure change in mean NRS-11 within each group. Analysis of covariance was used to compare the mean change in NRS-11 in the 2 groups. RESULTS: Morphine and loperamide were equivocal in pain relief after 12 and 24 hours (P = 0.400 and P = 0.753); however, the patient satisfaction scores were better in the morphine group. LIMITATIONS: The earlier studies performed used injectable forms of morphine, for the sake of comparison, we used powdered morphine and powdered Loperamide diluted with saline. Confounding variables include ulcer size and aetiology, which can be a source of bias. The ulcer size was not standardized due to the paucity of sample to study. Equianalgesic doses of loperamide and morphine could not be found even after an extensive literature search. The loperamide dose used in our case was equal to the dose used orally since the same dose appears effective across a range of oral opioid analgesics. The morphine dose was standardized as 10 mg based on a mixture previously used to treat pain due to epidermolysis bullosa. CONCLUSIONS: Topical loperamide can be an efficacious and novel intervention to treat painful ulcers while avoiding systemic effects. KEY WORDS: Loperamide, morphine, painful ulcer

The efficacy of intralesional injection of autologous platelet rich plasma versus normal saline dressing in chronic non-healing ulcers

Background: Platelet-rich plasma (PRP) can potentially enhance healing of chronic non-healing ulcer by increasing the delivery of various growth factors from the α-granules contained in platelets. Aim of this prospective randomized study was to evaluate the efficacy of autologous PRP versus normal saline (NS) at chronic non healing ulcer in relation to wound healing on the basis of ulcer size reduction, duration of healing, complete or partial healing and side effectsMethods: Fifty four patients with chronic non-healing ulcer were randomly divided into two equal groups: PRP group (treated with PRP) and NS group. Observations were made regarding pain, slough, discharge, granulation, reduction in ulcer size and volume on every 7th day till 4 weeks.Results: Reduction in area and volume of ulcers at the end of treatment was 12.27±4.10 cm2 and 6.88±5.26 cm3 in PRP group and 9.25±1.89 cm2 and 4.25 ±1.05 cm3 in NS group. In PRP group 59.25% had no discharge, 74.08% had no slough, 62.97% had no pain while in NS group no patient was without discharge, 14.81% patient had no slough, 74.07% had minimal pain on 28th day. In PRP group 22.22% ulcers were completely healed while in NS groups all ulcers were partially healed.Conclusions: PRP is more effective than NS on chronic non-healing ulcers as it causes more rapid healing, rapid relief from pain and early decrease in discharge and slough in all age groups and sex; irrespective of type, size, site, duration and etiology of ulcer.