Ulcer Healing Research Articles

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.

Functional ankle taping correction on plantar foot ulcer healing in diabetic patients: Randomized controlled trial

BACKGROUND: High pressure in diabetic foot plantar areas causes ulcer formation, leading to disability and amputations. Around 25% of diabetics experience foot ulcers, with prevalence rates varying among Africans, Asians, and Europeans. Egypt has the highest rates, ranging from 6.1% to 29.3%. OBJECTIVE: To investigate the impact of functional ankle taping correction on plantar foot ulcer healing in diabetic patients. METHODS: A double-blinded randomized controlled trial design. A total of 70 patients with plantar foot ulcers PFUs were randomly divided into two groups: group A, which received ankle taping in addition to usual medical therapy and debridement, and group B, which received ankle taping without routine medical treatment and debridement. Over two months, all patients underwent evaluation using a Walkway pressure monitoring system, goniometer, wound workstation, and saline injection. This evaluation aimed to determine maximal peak plantar pressure, active ankle dorsiflexion, wound area, and volume sequentially. RESULTS: Initially, there was no meaningful difference between the two groups. However, after eight weeks of treatment, there was a substantial impact, as indicated by a p-value of 0.001 and an f-value of 87.49 for treatment effect at 95% CI.Furthermore, a statistically significant interaction was found between treatment and time in the ankle-taping group between pre-and post-treatment. However, no difference was identified in the control group. CONCLUSIONS: The correction of ankle taping has a significant impact on various factors, including peak plantar pressure, ankle dorsiflexion, wound area, and wound volume. This correction leads to a reduction in peak plantar pressure, wound area, and volume while also enhancing active ankle dorsiflexion.

Antibacterial composite protein microneedle loaded with hypoxia-treated exosomes for oral ulcer healing

Oral ulcer treatment is challenging: various dressings have been developed, but they have poor efficacy. The efficacy of oral ulcer treatment depends on the local drug concentration; low drug concentrations result in slow wound healing. Therefore, the sustained release of active therapeutic ingredients from wound dressings with few administrations is promising. Hypoxic exosomes (Exos) can promote cell proliferation and angiogenesis. Further, silver nanoparticles (AgNPs) confer broad-spectrum antimicrobial effects. We prepared a light-cured composite microneedle (MN) patch based on bovine serum albumin methacryloyl (BSAMA) and methacrylic gelatin (GelMA) (the combination is denoted BG). Control, BG, BG@Exos, and BG@Exos&AgNPs were used to explore the therapeutic effects of hypoxic Exos and AgNPs on oral ulcers. In vitro experiments showed that BG@Exos&AgNPs MN patches effectively promoted cell migration, proliferation, and angiogenesis and significantly inhibited bacterial growth and expression of IL-2 and TNF-ɑ. We found that BG@Exos&AgNPs promoted the healing of oral ulcers in rats, demonstrated by rapid wound epithelial healing, downregulation of inflammatory factor expression, and increased macrophage polarization. Therefore, the designed BG@Exos&AgNPs MN patch is a valuable approach for treating oral ulcers.

Naltrexone accelerated oral traumatic ulcer healing and downregulated TLR-4/NF-kB pathway in Wistar rats

ObjectiveTo assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DesignWistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. ResultsThe 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). ConclusionNaltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.

Prognostic Ability of the Wound, Ischemia, Foot Infection (WIfI) Classification System in Diabetic Patients with Non-Healing Ulcer

Abstract Objectives Several classifications have been published to predict limb salvage in diabetic patients with non-healing ulcer to aid in the management plan. The Society for Vascular Surgery (SVS) Lower Extremity Guidelines Committee has composed a new classification system that reflects the three major factors that impact amputation risk and clinical management Our goal was to evaluate the predictive ability of this wound, ischemia and foot infection(WIfI) classification as a predictor of limb salvage in diabetic patients with non-healing ulcer Methods a prospective single arm observational cohort study conducted on 50 patients within 2022 at single center, Ain Shams University Hospitals, Patients are diabetics who had non healing ulcers some of the cases underwent angioplasty or debridement, then follow up of the wounds was done. Limbs were stratified into clinical stages 1 to 4 based on the SVS WIfI classification for amputation risk. Results Our study included 38 males (76%) and 12 females (24%). The age range between 35 years and 73 years with mean age of 59±8.81. All of the patients are diabetic. The percentage of patients with hypertensive ( 76 %), 54% of them were smoker &amp; 7 were suffering from ESRD. limb salvage was achieved on 75 % of cases. All cases have been classified according to WIFI classification into clinical stages I-IV and their percentage were 6%,12%,40% and 42% respectively. WIfI classification was significant in predicting the major or minor amputation as well as ulcer healing. As Major amputation among each WIfI classification group low, moderate and high risk was 0%, 10%, 47% respectively. Risk of minor amputation was 22%, 40% and 76% respectively. While ulcer healing was 100%, 85% and 52% respectively. Conclusion The likelihood of an amputation after one year in patients with non healing ulcer increases with higher WIfI stages, so The WIfI classification is applicable in prediction of limb salvage in diabetic patients with non-healing ulcer. Smoking and aging also decreases the chance of limb salvageability

Efficacy of surgical treatments for the management of solitary rectal ulcer syndrome: a network meta-analysis.

Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal bleeding, tenesmus, mucoid secretion, anal pain and a sense of incomplete evacuation. Diagnosis is based on characteristic clinical symptoms and endoscopic/histological findings. Several treatments have been reported in the literature with variable ulcer healing rates. This study aimed to evaluate the efficacy of different treatments for SRUS. A systematic review and network meta-analysis were performed according to the PRISMA guidelines. Studies in English, French and Spanish languages were included. Papers written in other languages were excluded. Other exclusion criteria were reviews, case reports or clinical series enrolling less than five patients, study duplications, no clinical data of interest and no article available. A systematic literature search was conducted from January 2000 to March 2024 using the following databases: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus. The biases of the studies were assessed using the Newcastle-Ottawa scale or the Jadad scale when appropriate. Types of treatment and their efficacy for the cure of SRUS were collected and critically assessed. The study's primary outcome was to estimate the rate of patients with ulcer healing. A total of 22 studies with 911 patients (men 361, women 550) diagnosed with SRUS were analysed in the final meta-analysis. The pooled effect estimates of treatment efficacy revealed that surgery showed the highest ulcer healing rate (70.5%; 95% CI 0.57-0.83). Surgery was superior in the cure of ulcers with respect to medical therapies and biofeedback (OR 0.09 and OR 0.14). Solitary rectal ulcer syndrome is a challenging clinical entity to manage. Proficient results have been reported with the surgical approach, suggesting its positive role in cases refractory to medical and biofeedback therapy. Further studies in homogeneous populations are required to evaluate the efficacy of surgery in this setting. (PROSPERO registration number CRD42022331422).

Surgical Offloading versus Medical Conservative Methods in Management of Diabetic Foot Plantar Ulcers (Interventional study)

Abstract Background As a result, peripheral neuropathy is frequently caused by diabetes (DM). Diabetic plantar foot pressure ulcers develop from the lack of protective pain sensibility as a result of recurrent shear and tear pressures. Relieving pressure on the foot's sole is necessary for the ulcers to heal. The purpose of the study is to compare the effectiveness of surgical and nonsurgical unloading procedures in the healing of plantar ulcers. Subjects and Methods 50 diabetic foot ulcer patients who visited Ain Shams University, the national institute of DM, and the endocrinology outpatient clinic participated in this interventional trial (NIDE). We employed mechanical and surgical unloading methods in this trial, and patients were monitored for 6 months to see how long it took for their injuries to recover. Results At the conclusion of the follow-up period, 88% of the surgical group's pressure ulcers were fully healed, compared to 86.7% of the non-surgical patients (6 months). Infection, recurrence, and non-healing were complications we encountered throughout the follow-up period. Regarding the treatment of plantar diabetic foot ulcers, offloading is crucial (DFUs). Compared to using only non-surgical methods, surgical offloading may hasten the recovery time. A well- trained team is necessary to prevent the issues with improperly fitting footwear and to teach the patient how to use them on a regular basis with the non-surgical offloading technique.

Hydroxypropyl Cellulose-Based Orally Dissolving Film Loaded with Insoluble Dexamethasone for Treatment of Oral Ulcers.

Oral ulcers present as recurrent and spontaneous lesions, often causing intolerable burning pain that significantly disrupts patients' daily lives and compromises their quality of life. In addressing this clinical challenge, oral dissolving films (ODFs) have emerged as promising pharmaceutical formulations for oral ulcer management due to their rapid onset of action, ease of administration, and portability. In this study, ODFs containing the insoluble drug dexamethasone (Dex) were formulated for the treatment of oral ulcers in rabbits using a solvent casting method with ethanol as the solvent. To optimize the composition of the ODFs, a Box-Behnken Design (BBD) experiment was employed to investigate the effects of varying concentrations of hydroxypropyl cellulose (HPC), low-substituted hydroxypropyl cellulose (L-HPC), and plasticizer (glycerol) on key parameters, such as disintegration time, tensile strength, and peel-off efficiency of the films. Subsequently, the film properties of the Dex-loaded ODFs (ODF@Dex) were thoroughly assessed, revealing favorable attributes, including homogeneity, mechanical strength, and solubility. Notably, the use of ethanol as the solvent in the ODF preparation facilitated the homogeneous distribution of insoluble drugs within the film matrix, thereby enhancing their solubility and dissolution rate. Leveraging the potent pharmacological activity of Dex, ODF@Dex was further evaluated for its efficacy in promoting ulcer healing and mitigating the expression of inflammatory factors both in vitro and in vivo. The findings demonstrated that the ODF@Dex exerted significant antiulcer effects by modulating the PI3K/Akt signaling pathway, thus contributing to ulcer resolution. In conclusion, our study underscores the potential of HPC-based ODFs formulated with ethanol as a solvent as a promising platform for delivering insoluble drugs, offering a viable strategy for the clinical management of oral ulcers.

The influence of socioeconomic factors on intervention and postoperative healing of venous ulcers: a prospective study.

In previous studies, venous ulcers (VUs) have been found to occur more often in patients with lower socioeconomic status. The aim of this study was to explore if socioeconomic factors influence the delay of referral to a vascular service or the time to healing after superficial venous intervention. In this prospective study, patients answered a questionnaire about the duration and recurrence of their VU, comorbidities, body mass index (BMI), smoking, alcohol, social and physical activities, ambulatory status, education, marital status, housing, perceived economic status and dependence on home care. Postoperative complications, VU healing and recurrence were noted one year after superficial venous intervention. A total of 63 patients were included in this study (30 females and 33 males), with a mean age of 71.2 years (range: 37-92 years). Duration of the present VU in patients was: <3 months in 48%; 3-6 months in 27%; 6-12 months in 11%; and >12 months in 14%. Risk factors for delayed referral were recurrent VU (odds ratio (OR): 4.92; p=0.021); walking impairment (OR: 5.43; p=0.009) and dependence on home care (OR: 4.89: p=0.039) in a univariable analysis. The latter was the only significant finding in a multivariable analysis with socioeconomic risk factor (OR: 4.89; p=0.035). In 85% of patients, their VU healed without recurrence during one year follow-up. Healing took longer if the patients: were of older age (p=0.033); had a normal BMI (independent samples t-test, p=0.028); had a recurrent VU (OR: 5.00; p=0.049); or walking impairment (Fishers exact test, OR: 9.14; p=0.008), but no significant socioeconomic risk factors were found. In this study, socioeconomic factors were not important risk factors for delayed referral of VU patients to a vascular service or prolonged healing time after superficial venous intervention. This work was supported by the Scandinavian Research Foundation for Varicose Veins and other Venous Diseases (SFÅV) and by ALF funding from Region Örebro County. The authors have no conflicts of interest to declare.

Comparison of the effect of combination therapies in the treatment of large varicose ulcers: A real-world cohort study.

The primary treatment for varicose ulcers is to address the underlying cause of venous hypertension, additionally, split-thickness skin transplantation (ST) is an effective option for large ulcers. The aim of this study was to compare the efficacy of venous surgery with or without split-thickness ST in the management of varicose ulcers (diameter ≥6 cm). Patients with varicose ulcers between 2013 and 2023 were included in the real-world retrospective cohort study. The endovenous microwave ablation/endovenous laser ablation-high ligation-foam sclerotherapy-compression therapy + ST group (EMA/EVLA-CT-HL-FS + ST) consisted of 32 patients, while the EMA/EVLA-CT-HL-FS group consisted of 48 patients. A difference in ulcer healing time was found between the two groups (the hazard ratio [HR] was 4.4, 95% CI [2.3-8.2], P < 0.0001). However, the healing rate did not differ between the two groups at 6 and 12 months postoperatively. ST has been shown to expedite ulcer healing and ameliorate the symptoms of VVs in the early stages of treatment, while its intermediate to long-term efficacy for ulcer healing and overall patient quality of life may be limited.

Single-center clinical experience of cyanoacrylate embolization method for incompetent perforating veins in treating CEAP-6 patients

ObjectiveThe most severe form of chronic venous insufficiency includes venous leg ulcers in the CEAP-6 stage. The aim of this study is to evaluate the relationship between incompetent perforator veins occluding with cyanoacrylate and closure of perforator veins and healing of venous leg ulcers in patients at the CEAP-6 stage. MethodsA total of 187 patients who underwent cyanoacrylate application to incompetent perforator veins due to venous leg ulcers from 2018 to 2021 were retrospectively reviewed. Twelve months after the procedure, patients were evaluated for perforator vein closure, ulcer diameter, and Venous Clinical Severity Scale. Receiver operating characteristic analysis was used to estimate the probability of postoperative nonocclusion of the perforating vein based on the preoperative ulcers’ diameters and the perforating veins’ mean diameters. Univariate and multivariate binary logistic regression analyses were conducted to identify the risk factors associated with incomplete closure of the perforating vein. ResultsAt the 12 months, 87.1% of patients experienced incompetent perforator veins closure, leading to complete healing of venous leg ulcers. Preoperative ulcer diameter significantly decreased from 7.20 ± 3.48 cm2 to 0.28 ± 0.77 cm2 after the procedure (P < .001). On average, 3.5 ± 1.01 perforating veins were treated, with a diameter of 4.09 ± 0.41 mm. No postoperative paresthesia or deep vein thrombosis occurred. Preoperative Venous Clinical Severity Scale scores decreased significantly from 17.85 ± 3.06 to 8.03 ± 3.53 postoperatively (P < .001). Patients with nonoccluded perforating veins had larger preoperative ulcer diameters (13.77 ± 1.78 cm2) than those with occluded perforating veins (6.24 ± 2.47 cm2; P < .001). The mean perforating vein diameter was also larger in nonoccluded perforating veins patients (4.45 ± 0.41 mm) than in occluded perforating veins patients (4.04 ± 0.38 mm; P < .001). The sensitivity, specificity, and accuracy of the preoperative ulcer diameter cutoff point of 11.25 cm2 for the possibility of postoperative nonocclusion of perforating veins were 100% each. In contrast, those for the preoperative mean perforating vein diameter cutoff point of 4.15 mm were determined as 66.7%, 79.1%, and 77.5%, respectively. The presence of diabetes mellitus increased the likelihood of incompetent perforator veins, remaining open by 3.4 times (95% confidence interval: 1.11-10.44; P = .032), whereas a 1 mm larger mean perforating vein diameter increased this likelihood by 9.36 times (95% confidence interval: 3.47-25.29; P < .001). ConclusionsThis study demonstrates that occlusion of incompetent perforator veins with cyanoacrylate is effective, safe, and associated with low complication rates in CEAP-6 patients. The findings support that cyanoacrylate occlusion of perforator veins may be a valuable option in the treatment of venous leg ulcers.

Relaxation intervention to improve diabetic foot ulcer healing: protocol for a pilot study with a nested qualitative study.

A mixed-methods approach nested in a pilot three-arm randomised controlled trial (RCT) was conducted to evaluate the feasibility and acceptability of an intervention of progressive muscle relaxation with guided imagery (experimental group) compared to a neutral guided imagery placebo (active control group) and a group that did not receive any psychological intervention (passive control group). The purpose was to inform a future definitive RCT that will test its effectiveness. Qualitatively, this study examined patients and health professionals' perspectives regarding the relaxation intervention, in order to assess the acceptability and applicability of relaxation as an adjuvant therapy. Participants must have had a diagnosis of diabetes and diabetic foot disease; one or two active hard-to-heal ulcers at the time of the assessment; and clinical levels of stress or anxiety or depression. Participants were randomised and assessed at three timepoints after the first hospital consultation for hard-to-heal diabetic foot ulcer (DFU). Rates of eligibility, recruitment, refusal, adherence to study protocol, participation in follow-up and dropout, and patients' satisfaction with the relaxation intervention were assessed as primary outcomes. Secondary outcomes were DFU healing; patients' DFU-related quality of life; physical and mental quality of life; perceived stress; emotional distress; adherence to DFU care; perceptions of DFU; as well as arterial systolic/diastolic pressure and heart rate. The results of this pilot study contributed to clarification and better elucidation of the benefits of relaxation techniques regarding patients' HRQoL and DFU healing. Funding: This study was conducted at the Psychology Research Centre (CIPsi/UM) School of Psychology, University of Minho, Portugal and supported by the Foundation for Science and Technology (FCT) through the Portuguese State Budget (UIDB/01662/2020) and by a PhD fellowship from FCT assigned to GF (SFRH/BD/131780/2017) and an FCT grant (PTDC/PSI-GER/28163/2017) assigned to MGP. The authors have no conflicts of interest to declare.

Evaluating the effects of digital stromal vascular fraction injections in systemic sclerosis patients: a retrospective study

ObjectiveManaging hand symptoms in patients with systemic sclerosis is difficult, and the current treatments often provide only limited relief of. In 2014 a new treatment for theses patients was proposed for improving hand function, namely the digital injection of adipose tissue derived stem cells.MethodsFrom 2015 to 2017 seven systemic sclerosis patients with an impaired hand function were treated with the aforesaid injections. A medical chart review was performed to collect pre- and postoperative patient specific data.ResultsOur findings indicated no significant improvement in nailfold capillaroscopic measurements or in the healing of preexisting digital ulcers. Additionally, patients reported a slight worsening in hand function after the treatment. However, we observed a decrease in the modified Rodnan skin score, which measures skin thickness Although previous research has verified the safety and feasibility of this treatment, we found no definitive evidence of its effectiveness.ConclusionOur results suggest that the specific conditions under which this treatment could be beneficial need to be identified through randomized controlled trials involving larger groups of patients.Level of Evidence:Level IV, therapeuticstudy.

Periplaneta americana extract promotes infectious diabetic ulcers wound healing by downregulation of LINC01133/SLAMF9

Wound healing in diabetic ulcers remains a significant clinical challenge, primarily due to bacterial infection and impaired angiogenesis. Periplaneta americana extract (PAE) has been widely used to treat diabetic wounds, yet its underlying mechanisms are not fully understood. This study aimed to elucidate these mechanisms by analyzing long non-coding RNA (lncRNA) expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE, using high-throughput sequencing. Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor (hM-CSF) and subsequently polarized into M1 macrophages with lipopolysaccharide. The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE. Furthermore, PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and angiogenesis. These effects were diminished when LINC01133 or SLAMF9 were overexpressed. Mechanistically, LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1. Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions. In conclusion, PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.