Ulcer Healing Research Articles

Hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway-based ulcer-healing mechanism of Astragalus Aqueous extract in diabetic foot rats.

The main objective of this work was to investigate the mechanism of Astragalus aqueous extract ulcer healing in diabetic foot model rats through the hypoxia-inducible factor 1-alpha (HIF-1ɑ)/vascular endothelial growth factor (VEGF) signalling pathway. Fifty specific-pathogen-free male Sprague Dawley rats were divided into blank (A), model control (B), Astragalus extract (C) and mupirocin (D) treatment groups. Group A received a regular diet, whereas the other groups received a high-fat/high-sugar diet and intraperitoneal streptozotocin injections to induce diabetes. Diabetic foot ulcers were created via skin excision. Subsequently, ulcers were debrided daily. Groups B, C and D received wet saline gauze, wet gauze with Astragalus extract and gauze with mupirocin, respectively, on the affected area. Group A received no treatment. After 14days, the rats were assessed for ulcer healing and general condition. Immunohistochemistry was used to detect HIF-1ɑ and VEGF levels in the dorsalis pedis artery, and ELISA was used to determine serum IL-6 and CRP levels. The results revealed that Groups C and D had significantly faster ulcer healing compared with Group B (p < 0.01), and ulcer healing was faster in Group C than in Group D (p < 0.01). Group C exhibited notably higher HIF-1ɑ and VEGF protein expression levels compared with Groups B and D (p < 0.01). IL-6 and CRP expression levels in Groups C and D were significantly lower than those in Group B (p < 0.01). In summary, Astragalus aqueous extract effectively treats diabetic foot ulcers by up-regulating HIF-1ɑ and VEGF expression, activating the HIF-1ɑ/VEGF pathway, improving local tissue ischaemia and hypoxia, promoting collateral circulation and enhancing dorsalis pedis artery formation, thereby accelerating ulcer repair in diabetic rats.

Neonatal Riga-Fede disease: A systematic review of 84 cases collected over 120 years

Background: Traumatic ulceration of the tongue due to congenital teeth is known as Riga-Fede disease (RFD). The literature on RFD consists largely of anecdotal case reports, thereby lacking valid clinical recommendations. While managing a newborn with RFD complicated by Ludwig’s angina, this knowledge gap was recognized. Therefore, this systematic review was conducted to gain insight into the optimal management and the possible complications of RFD. Methods: A literature search was conducted using PubMed, Google Scholar, and Science Direct, supplemented with African Journals Online, Indmed, and manual searches. Papers published between 1900 and July 2023 in any language were retrieved. Neonates with natal or neonatal teeth and ulceration of the oral mucosa were included. Papers with incomplete data and review articles were excluded. Results: A total of 84 newborns with RFD from 62 published reports (including the case reported herein) were analyzed. Most of the reports were from the Indian subcontinent, and the frequency of reporting has increased since the year 2000. Tongue ulceration in all cases was due to mandibular incisors. There was no significant difference in the median duration of healing between the tooth extraction group (14 days) and the conservative management group (18 days). There was only a very weak positive correlation between the duration of symptoms and healing time, which was statistically insignificant. Conclusion: Healing of mucosal ulcers in RFD is often protracted and does not appear to be influenced by the duration of symptoms or by the modality of treatment. Extraction of the offending teeth is more common (75% of cases) than conservative management, such as grinding (ameloplasty) or resin capping of teeth. RFD is mostly a benign disorder; however, serious complications such as meningitis, Ludwig’s angina, and soft tissue abscesses can rarely occur with Staphylococcus aureus infections.

Innovative Self Nano‐Emulsifying Drug Delivery Systems for Peptic Ulcer Therapy: A Review

AbstractPeptic ulcer disease (PUD) adversely affects ≈4 million individuals globally and remains pervasive among 5–10% of the general population. Mucosal lesions prompted by the ulceration lead to the penetration through mucosal layers, ultimately resulting in cavity formation and inflammation. Conventional therapeutic modalities for peptic ulcers have shown unfavorable effects, relapses, and numerous drug interactions. The genesis of gastric ulcers is catalyzed via an imbalanced interplay between environmental lesions, defensive mechanisms, and the restoration of gastric mucosa. Lipid based nanotechnology involved in self‐nanoemulsifying drug delivery system (SNEDDS) is being tremendously involved in opening avenues in innovative pharmaceutical delivery systems in terms of improving solubility and regenerative healing against peptic ulcers. Biological macromolecules can be incorporated into SNEDDS to embellish the drug delivery system on an advanced level. Herein, in this review, the potential of SNEDDS as a viable carrier for administering biomacromolecules for regenerative healing in ulcers is discussed in detail.

Prognostic Performance of the Maximal Systolic Acceleration at the Hallux in Healing of Foot Ulcers: A Retrospective Cohort Study

The accurate prediction of foot ulcer healing remains a major challenge in clinical practice. To date, no reliable bedside tests are available. The primary aim of this study was to determine the prognostic performance of the maximal systolic acceleration (ACCmax) to predict ulcer healing. Secondary objectives comprised the investigation of the prognostic accuracy in patients prone to medial arterial calcification and to assess the potential risk of amputation. A single-center retrospective cohort study was conducted. Patients aged ≥18 years who presented with a new-onset ulcer (i.e. Fontaine IV and neuropathic ulcers) on the foot and underwent an ACCmax measurement at the hallux were included. Ulcer healing was defined as an intact skin with epithelialization after 3 or 12months of follow-up. Prognostic performance was calculated by using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). In total, 136 patients with 143 wounds were included. Almost half of the patients were diagnosed with diabetes mellitus (47%), and wound infection was present in 42% of cases. After 3months of follow-up, an NPV of 97.9%, PLR of 3.25, and NLR of 0.19 were found when applying an ACCmax threshold of 0.5m/s2. When looking at 12months, these numbers were 85.6%, 2.72, and 0.50, respectively. Subgroup analysis for patients with diabetes mellitus and chronic kidney disease showed comparable results. The risk of amputation increased significantly when a measurement below 1.0m/s2 was present (odd ratio 5.3, P=0.010). ACCmax measurements at the hallux can have additional prognostic value in patients with foot ulcers. An ACCmax below 1.0m/s2 is associated with nonhealing of an ulcer and a higher risk of amputation, while higher ACCmax values are associated with limb salvage. Therefore, ACCmax could be used for grading ischemia in a wound classification system.

Protective effect of dimethyl fumarate against ethanol-provoked gastric ulcers in rats via regulation of HMGB1/TLR4/NF-κB, and PPARγ/SIRT1/Nrf2 pathways: Involvement of miR-34a-5p

Aberration of the gastric mucosal barrier homeostasis circuit is one of the key features linked to the onset of gastric ulcers (GU). This work aimed to inspect the gastroprotective influence of dimethyl fumarate (DMF) on ethanol-induced GU in rats and to decipher the possible mechanisms entailed. Rats were pretreated with either DMF (80 mg/kg) or omeprazole (OMP) (20 mg/kg) by oral gavage for 2 weeks. After 24 h of starvation, ethanol (5 ml/kg, oral) was employed to trigger GU in rats, while carboxymethyl cellulose (CMC) was used as a control. Ethanol notably elevated both macroscopic and microscopic gastric damage. DMF and OMP exhibited similar effects on gastric ulcer healing. DMF intervention led to a substantial improvement in gastric insults. DMF significantly reduced ethanol-triggered gastric lesions, as manifested by decreased gastric secretion, acidity, ulcer surface area percent, reduced leukocyte incursion, and increased mucus percent. DMF upregulated miR-34a-5p expression concomitant with the suppression of high mobility group box1 (HMGB1) and inflammatory responses in gastric mucosal homogenate. DMF improved GU by restoring reduced antioxidant defense mechanisms through the coactivation of nuclear factor erythroid 2-related factor-2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPARγ), and sirtuin1 (SIRT1), indicating the protective role of the PPARγ/SIRT1/Nrf2 pathway. Intriguingly, DMF mitigated apoptosis in ethanol-elicited GU. Taken together, this research implies the potential for the repurposing of DMF as an innovative gastroprotective medication to reestablish the balance of the gastric mucosal barrier via the attenuation of gastric inflammation, oxidative stress, and apoptosis.

Intra-Arterial Nitroglycerin Injection in Upper Extremity Buerger's Disease for Faster Ulcer Recovery: A Case Report

AbstractThromboangiitis obliterans (TAO), also known as Buerger's disease, is a challenging nonatherosclerotic vascular disorder predominantly affecting smokers. Current management of TAO lacks standard guidelines, with smoking cessation as the only cornerstone. We present the case of a 28-year-old smoker with TAO manifesting as necrotic finger ulcers. Regardless of initial debridement, conventional therapy failed to improve his condition. Angiography confirmed the diagnosis of TAO and intra-arterial nitroglycerin injection was administered, leading to immediate vasodilation and improved perfusion. Combined with oral vasodilators and anticoagulants, the patient showed significant ulcer healing within 2 weeks. TAO's etiology remains unclear; however, it is linked to smoking and immune responses. Diagnosis relies on clinical criteria and angiographic findings. While smoking cessation remains crucial, various pharmacological interventions like vasodilators show considerable potential for enhancing therapeutic outcomes. Our case highlights the potential of intra-arterial nitroglycerin in TAO management. However, further studies are warranted due to limited sample size. Advancements in understanding TAO's biology and diagnostic techniques offer hope for improved management strategies in the future.

Axial Ablation versus Terminal Interruption of the Reflux Source (AAVTIRS): A Randomised Controlled Trial.

Treatment of reflux has been shown to improve time to healing of Venous Leg Ulcers (VLU). Terminal Interruption of the Reflux Source (TIRS) treats reflux within the plexus of veins around an active VLU using foam sclerotherapy. The efficacy of TIRS in managing VLU has never been tested. We performed a pragmatic, single centre, assessor-blinded, randomised controlled trial comparing endovenous ablation of the axial superficial veins (Axial Ablation-AA) vs TIRS. Patients of any age with VLU of any duration were eligible. 98 Participants were randomised to AA or TIRS. 39/55, 70.9% (95%CI; 57.1-82.37) healed their VLU in the AA group, while 29/39, 74.36% (95%CI; 57.87-86.96) healed their VLU in the TIRS group, P = 0.45.4 were lost to follow-up. Median time to ulcer healing was 84 days (95%CI; 74.67-93.33) in the axial ablation group and 84 days (95%CI; 73.02-94.98) in the TIRS group. Hazard Ratio for ulcer healing with AA vs TIRS was 0.96 (95%CI 0.59-1.56). There were no significant quality of life differences. The AAVTIRS trial did not show that axial ablation was superior to TIRS in the primary outcome of number of VLU healed in 6 months, or time to VLU healing. This trial is not powered to show non-inferiority. TIRS is a viable option for treatment of VLU. Further investigation is necessary before it can be recommended as an alternative to axial ablation.Trial registered at clinicaltrials.gov NCT04484168.

Protocolized Foot Exercises Help in Improvement of Diabetic Foot Ulcers and Quality of Life When Added to Standard Therapy-A Randomized Clinical Trial.

Diabetic foot disease is the major cause of nontraumatic limb amputations worldwide causing a high socioeconomic and psychological toll and a huge burden to the healthcare system. Currently, standard treatment of diabetic foot ulcer is through multidisciplinary therapy. Foot exercises have been shown to improve healing in diabetic ulcers although evidence is limited and applicability is non-uniform. Our study aimed to generate more evidence regarding the benefit of addition of protocolized foot exercises so that it can be instituted as a standard of care. It was an open label Randomized controlled trial with seventy-two patients and study duration of one and half years Patients with diabetic foot ulcers were randomized into two groups. Both groups received standard therapy for diabetic foot ulcer. The intervention group in addition received three months of protocolized foot exercises. At the end of three months ulcer healing and quality of life were m compared among both the groups. Regular exercises for three months caused significant reduction in ulcer area compared to the non-intervention group [100% versus 45.22%, 95% CI =36.30(16.04-56.56), P-value = 0.001]. Quality of life analyzed by SF-36 score showed significant improvement in components like physical function [69.4 ± 8.9 versus 63.7 ± 11.0, 95% CI = 5.73 (0.97-10.48), P-value = 0.01], emotional well-being [65.2 ± 7.6 versus 60.8 ± 7.9, 95% CI = 4.44 (0.79-8.10), P-value = 0.01], and pain components [55.4 ± 18.5 versus 47.5 ± 14.5, 95% CI = 7.99 (0.16-15.81), P-value = 0.04) at 3 months although change in social functioning, physical health limitation, health change, energy and general health improvement were not significant. Addition of protocolized foot exercises are beneficial for patients of diabetic foot ulcers in terms of ulcer healing as well as improvement of quality of life provided compliance to exercises can be ensured.

Effect of Using Photobiomodulation (660 Nanometers) for the Treatment of Diabetic Ulcers: Protocol for a Randomized Controlled Trial.

Diabetic foot ulcers (DFUs) result in tissue damage or impairment of deeper structures that affect quality of life. The impacts are numerous, and even after a long treatment period, 65% of patients experience recurrence. Among the interventions used to accelerate the healing process of DFUs, photobiomodulation therapy (PBMT) is a painless, noninvasive, and low-cost treatment. To achieve effective therapeutic results optimal PBMT parameters are necessary. The positive effect of PBMT on diabetic cells may be dependent on fluence (J/cm2) and wavelength (nm). This double-blind, randomized clinical trial will be conducted at the University Clinic of Physical Therapy. One hundred patients will be randomly placed in 4 groups. A Laserpulse Ibramed (Helium-Neon, HeNe, 660 nm) with 20 W power will be used (continuous mode), with doses stipulated for each treatment group (GL1, 4 J/cm2; GL2, 8 J/cm2; GL3, 12 J/cm2) and Endophoton KLD GaAs 904 nm (ST, 10 J/cm2) for 2 nonconsecutive days per week for 10 weeks, for a total of 20 sessions. The primary outcomes will be ulcer healing rate and University of Texas classification scores. Patients' DFUs will be assessed on the 1st day, 5 weeks, and 10 weeks of treatment then 1 month after the end of treatment. This study may aid effective clinical decision-making for the management of DFUs.

Advancements in Natural Alkaloid-Loaded Drug Delivery Systems for Enhanced Peptic Ulcer Treatment: A Review

Abstract: Peptic ulcers, which damage the gastrointestinal tract lining, are a significant global health issue. The traditional approaches to treating peptic ulcers have poor bioavailability, unstable formulations, and undesirable side effects. Natural alkaloids have garnered increased interest as potential therapeutic agents in recent years due to their diverse pharmacological actions and decreased toxicity profiles. This manuscript summarizes recent progress in natural alkaloids for peptic ulcer treatment, highlighting new drug delivery methods. Natural alkaloids, originating from different plants, have anti-inflammatory, antioxidant, and antibacterial properties, potentially accelerating the healing of peptic ulcers. Moreover, medicines don't always function properly because they degrade too fast, don't dissolve well, and have other problems, such as insufficient bioavailability. Creative liposome delivery systems, microspheres, nanocarriers, and other customized delivery strategies have shown promise in overcoming these barriers. By distributing the medication gradually and precisely, these innovative techniques improve the medication and effectiveness at the ulcer site. As a result, natural ingredients work better and provide better treatment results.

Design and optimization of pantoprazole sodium mucoadhesive hydrogel microcapsules for the healing of peptic ulcers

Design and optimization of pantoprazole sodium mucoadhesive hydrogel microcapsules for the healing of peptic ulcers

Percutaneous transluminal angioplasty of femoropopliteal veins for treatment of post-thrombotic syndrome.

Background: Controversy persists concerning the endovascular treatment of the post-thrombotic syndrome (PTS), particularly if femoropopliteal veins are involved. Methods: We screened consecutive patients with PTS who underwent percutaneous transluminal angioplasty (PTA) of femoropopliteal veins using posterior tibial or popliteal vein access who had at least 3-month follow-up. Our assessment included the evaluation of primary and secondary patency of the treated segments by Doppler ultrasound (DUS) and clinical outcomes measured by the change in Villalta score as well as ulcer healing. Results: Among 29 patients, 8 (27.7%) were women and the mean (SD) age was 53.3 (13.6) years. Posterior tibial vein and popliteal access were used in 26 (89.7%) and 3 patients (10.3%), respectively. 13 (44.8%) patients had prior (n = 11, 37.9%) or concomitant (n = 9, 31.0%) endovascular treatment of the iliac or common femoral veins. At a median follow-up of 395 days (Q1: 205-Q3: 756 days), primary patency of femoropopliteal veins was 79.3% (95% CI 64.6-94.1%) and secondary patency was 82.8% (95% CI, 69.0-96.5%). The percentage of patients with moderate or severe PTS according to the Villalta score decreased from baseline to last follow-up from 34.5% to 18.5% and from 31% to 14.8%, respectively (p<0.003). Overall, the mean (SD) Villalta score decreased from 11.5 (1.7) to 8.0 (1.7) (p<0.0001). Postprocedural complete ulcer healing occurred in 4 out of 5 (80%) patients. Two (6.9%) patients developed new ulcers. No major bleeding, pulmonary embolism, stroke, or death occurred. Conclusion: PTA of femoropopliteal veins via posterior tibial or popliteal vein access appears to improve the severity of PTS with acceptable patency rates.

Enhancing the efficacy of fluconazole against Leishmania major: Formulation and evaluation of FLZ-nanoemulsions for topical delivery

BackgroundCutaneous Leishmaniasis (CL) remains a significant public health concern, particularly in the tropical and subtropical regions. Present treatment options for CL such as Fluconazole (FLZ) face limitations, including low solubility and bioavailability. This study aimed to address these challenges by investigating the use of nano-emulsions (NEs) to enhance the efficacy of FLZ against Leishmania major(L.major). Materials and methodsFLZ-NEs were formulated with oleic acid, Tween-20, and ethanol using low-energy emulsification at various surfactant/co-surfactant ratios. Subsequently, a comprehensive analysis was conducted to assess the physicochemical characteristics of the samples. This analysis encompassed stability, zeta potential, pH, viscosity, refractive index, and droplet size. We then studied the anti-parasitic properties of these optimized FLZ-NEs both in vitro and in vivo. ResultsThe selected nano-emulsion (NE) formulation (2 % oleic acid, 20 % Tween 20, 10 % ethyl alcohol) showcased desirable properties like small droplet size (10.51 ± 0.24 nm), low dispersity (0.19 ± 0.03), and zeta potential value (- 0.41 ± 0.17 mV), key for stability and targeted drug delivery. This optimal formulation translated into remarkable efficacy. In vitro, FLZ-NEs demonstrated a threefold increase in their ability to combat promastigotes and a remarkable thirtyfold increase in their ability to combat amastigotes. Additionally, they demonstrated a ninefold advantage in their ability to specifically target parasites within infected macrophages, thereby attacking the infection site. These promising in vitro results translated into improved outcomes in vivo. Compared to other chemicals studied, FLZ-NE-treated mice showed decreased disease severity, weight growth, and quicker ulcer healing. It was further supported by histopathological research, which showed reduced tissue damage linked to Leishmania infection. ConclusionThese findings show the potential of nanotechnology-based drug delivery in improving anti-leishmanial treatment.

Doxycycline-loaded carboxymethyl cellulose/sodium alginate/gelatin hydrogel: An approach for enhancing pressure ulcer healing in a rat model.

Pressure ulcers, or bedsores, are created by areas of the skin under prolonged pressure and can lead to skin and underlying tissue damage. The present study evaluated the effects of carboxymethyl cellulose/sodium alginate/gelatin (CMC/Alg/Gel) hydrogel containing doxycycline (DOX) on improving the healing process of pressure ulcers. The magnet was used to apply pressure on the dorsum skin rat to induce a pressure ulcer model. Then sterile gauze, CMC/Alg/Gel, and CMC/Alg/Gel/1% w/v DOX hydrogels were used to cover the wounds. Blood compatibility, weight loss, cytocompatibility, drug release rate, cell viability, wound closure, and re-epithelialization were evaluated in all animals on the 14th day after treatment. In vivo results and histopathological evaluation showed 56.66% wound closure and the highest re-epithelialization in the CMC/Alg/Gel/1% w/v DOX hydrogel group (14 days after treatment). Furthermore, real-time PCR results indicated that the hydrogel containing DOX significantly decreased the expression of the MMP family consisting of MMP2 and MMP9 mRNA and also increased the expression of vascular endothelial growth factor VEGF mRNA. This study suggested that the addition of DOX, an antibiotic and MMP inhibitor, to hydrogels may be effective in the healing process of pressure ulcers.

Silk Fibroin Microneedles Loaded with Lipopolysaccharide-Pretreated Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Oral Ulcer Treatment.

Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn2+, which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.

Association of Tryptophan/Kynurenine Metabolites with Healing in Chronic Venous Leg Ulcers.

Objective: Chronic wound healing is a complex process that is still not well understood. The tryptophan (TRP)-l-kynurenine (KYN) pathway has recently been under increased scrutiny with regard to wound healing. The study applied metabolomics to elucidate the TRP-l-KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). Approach: This study used a longitudinal comparative design of 60 serum samples collected from 30 older adult patients with CVLUs, receiving weekly sharp debridement at a wound clinic. The serum samples were collected at baseline and week 4 (healed wounds) or week 8 (nonhealed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was used to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. Results: The mean age was 71.13 (±9.46 years). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the nonhealed group were consistently lower than those for the healed group. The healed group (n = 12) had higher KYN values. Those on a healing trajectory (n = 23) had lower KYN levels and higher TRP levels at baseline and over time. There was moderate support (Bayes factor = 3.70) for a negative association between change in kynurenic acid and linear healing slope (r = -0.35, credibility intervals [CrI] = -0.62, -0.04; probability of direction [PD] = 98%). Results suggest that KYN and TRP may be markers for healing in individuals with CVLUs. Innovation and Conclusion: Gaining a better understanding of the associations between the TRP-l-KYN pathway and the healing of CVLUs may help to clarify the links of inflammation with the rate and success of wound healing. Biomarker development focused on the TRP-l-KYN pathway could be pursued, if the associations are further supported by focused research studies.

The impact of statin therapy on the healing of diabetic foot ulcers: a case–control series

BackgroundDiabetic foot ulcers (DFU) are a costly complication of diabetes mellitus (DM), with significant implications for the patient and the healthcare professionals that treat them. The primary objective of this study was to evaluate if there were improved healing rates in patients with a DFU that were taking a statin medication compared to those patients with a DFU who were not taking a statin medication. Secondary outcomes assessed were correlations with wound healing or statin use on data obtained from retrospective chart review.MethodsA case–control series was performed to obtain appropriate demographic information, comorbid conditions, laboratory values, and physical examination findings. From the time of presentation with DFU, these patients were followed for 12 weeks to evaluate for healing. Healing was defined as full epithelialization of the DFU with no further drainage. Wound healing and statin use correlation testing was then done for collected variables and each cohort. Chi square and Pearson correlation were then performed to identify any significant correlations. All p-values were two-sided, and findings were considered statistically significant at p < 0.05.ResultsOur study identified 109 patients, 75 patients with a DFU on statin medication and 34 patients with a DFU not on statin medication. The statin cohort was more likely to be older, less than 5-year duration of diabetes, have more comorbidities, decreased low-density lipoprotein (LDL) cholesterol, and decreased total cholesterol (p < 0.05). Among those patients taking a statin medication, 48.0% (36/75) healed their DFU within 12 weeks. Among those patients not taking a statin medication, 44.1% (15/34) healed their DFU within 12 weeks. No correlation was noted between wound healing and statin use (p = 0.7). For wound healing, a negative correlation was noted for prior minor amputations (p < 0.05). For statin use, correlations were noted for age, duration of DM, LDL cholesterol level, total cholesterol level, HTN, CAD, and HLD (p < 0.05).ConclusionsStatin medication use did not influence DFU healing rates between cohorts. There was a correlation noted between wound healing and prior minor amputations and between statin use and age, duration of DM, LDL cholesterol, total cholesterol, HTN, CAD and HLD. Additionally, we observed no correlation between DFU healing rates and use of a statin medication.

Effect of Medical Ozone Therapy in Preventing Compromised Nasal Skin in Revision Rhinoplasty.

Ozone is often used as an additive therapy for skin conditions like infectious diseases, wound healing, diabetic foot, and pressure ulcers. The viability of the nasal skin has crucial importance in revision rhinoplasty cases. The study investigates the potential benefits of medical ozone therapy in healing the nasal skin in multiple-operated cases. The study retrospectively examined 523 revision rhinoplasty patients operated by the first author from January 2017 to January 2024. Patients consenting to ozone therapy received 3 major autohemotherapy sessions post-surgery. Patients were divided into 2 groups: those with compromised nasal skin (infection, poor vascular supply) and those with normal healing. Age, gender, smoking, diabetes, previous surgeries, grafting materials, and techniques were considered. Of the 523 patients, 12 (2.3%) experienced major skin complications like infection and necrosis, while 511 (97.7%) had no or minor issues, such as discoloration. In total, 301 patients accepted and received ozone therapy. Of the patients without major complications, 299 (58.3%) received ozone therapy, while 212 (41.7%) did not. Among the 12 with major complications, two (16.7%) received ozone therapy, and the remaining 10 (83.3%) did not. Ozone therapy recipients showed statistically fewer skin problems (p<0.05). Costal cartilage as tip and septal extension graft was linked to skin issues (p<0.05). No major adverse effects from ozone therapy were noted. Our findings indicate that ozone therapy may be a safe and potentially effective option for patients undergoing revision rhinoplasty, especially those with compromised nasal skin. It appears to aid in skin healing and regeneration, possibly through enhancing oxygen delivery and modulation of the immune response. Ozone therapy is a promising adjunct treatment for managing skin complications in revision rhinoplasty patients. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

METTL3-mediated NDUFB5 m6A modification promotes cell migration and mitochondrial respiration to promote the wound healing of diabetic foot ulcer

BackgroundDiabetic foot ulcer (DFU) is the most devastating complication of diabetes mellitus (DM) and plays a major role in disability and death in DM patients. NADH: ubiquinone oxidoreductase subunit B5 (NDUFB5) plays an important role in maintaining mitochondrial respiration, but whether it is involved in regulating the progression of advanced glycation end products (AGEs)-mediated DFU is still unclear.MethodsFirstly, the role of AGEs on cell viability, migration, and mitochondrial respiration in human umbilical vein endothelial cells (HUVECs) was explored in vitro. Next, NDUFB5 expression was detected in human samples and AGEs-treated HUVECs, and NDUFB5’s effect on AGEs-induced HUVECs injury and skin wound in diabetic mice was further clarified. In addition, the role of m6A modification mediated by methyltransferase-like 3 (METTL3) in regulating NDUFB5 expression and AGEs-induced HUVECs injury was investigated.ResultsNDUFB5 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs, whereas mitochondrial fusion promoter M1 facilitated cell viability, migration, and mitochondrial oxiadative respiration in NDUFB5 knockdown HUVECs. Meanwhile, NDUFB5 promotes skin wound healing in diabetic mice. Besides, METTL3-mediated m6A modification and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced NDUFB5 expression in HUVECs. Furthermore, METTL3 promoted cell viability, migration, and mitochondrial respiration in AGEs-treated HUVECs by increasing NDUFB5.ConclusionMETTL3-mediated NDUFB5 m6A modification inhibits AGEs-induced cell injury in HUVECs. METTL3 and NDUFB5 might serve as potential targets for DFU therapy in the future.

Efficacy of tibial cortex transverse transport in treating diabetic foot ulcer and its effect on serum omentin-1 and irisin levels

ObjectiveDiabetic foot ulcer (DFU) is a common and debilitating complication of diabetes that is associated with an increased risk of lower-limb amputation and a reduced life expectancy. Tibial cortex transverse transport (TTT) has become a newly alternative surgical method to facilitate ulcer healing and prevent lower limb amputation. Herein, we investigated the efficacy of TTT in treating DFU and changes of serum omentin-1 and irisin levels.MethodsThis study prospectively recruited 52 consecutive patients with DFU who were treated with TTT. The follow-up was performed weekly during the first 12 weeks postoperatively and every 3 months until 1 year after TTT. The serum levels of vascular endothelial growth factor (VEGF), omentin-1, and irisin in DFU patients undergoing TTT were determined by ELISA methods on the preoperative 1st day, postoperative 2nd week and 4th week.ResultsThe wound healing rate was 92.3% (48/52) at the 1-year follow-up. The visual analog scale (VAS) pain scores of patients showed a significant reduction at the 4th week after TTT (p < 0.001). The dorsal foot skin temperature, ankle brachial index, and dorsal foot blood flow of patients were significantly increased at the 4th week after TTT (p < 0.001). Results of ELISA methods showed the serum levels of VEGF, omentin-1, and irisin on the 2nd week and 4th week after TTT were notably elevated compared to the levels determined on the preoperative 1st day (p < 0.001). The serum levels of VEGF, omentin-1, and irisin on the 4th week after TTT were also significantly higher than the levels determined on the 2nd week after TTT (p < 0.001).ConclusionTTT could promote the wound healing and reduce the risk of lower limb amputation, demonstrating promising clinical benefits in the treatment of DFU. Increased expressions of serum proangiogenic factors including VEGF, omentin-1, and irisin were noted in the early stage after TTT, which may provide a new mechanism of TTT promoting wound heal.