Ulcer Healing Research Articles

Gastric MALT Lymphoma with Giant Ulcer from Untreated H. pylori: Role of Endoscopic Biopsy – A Case Report.

Introduction: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare extranodal non-Hodgkin lymphoma strongly linked to Helicobacter pylori infection. It often presents with nonspecific symptoms like dyspepsia, nausea, and epigastric pain and can mimic other gastric pathologies, such as peptic ulcers or gastric cancer. This case report is significant as it highlights the importance of thorough biopsy procedures in diagnosing gastric MALT lymphoma. The patient presented with complaints of dyspepsia, nausea, and epigastralgia and had a giant ulcer on endoscopy. Only after biopsies with a large number of samples (over 10) from both normal and abnormal mucosa the diagnosis of MALT lymphoma was established and reconfirmed after immunohistochemistry. The presence of Helicobacter pylori was detected, and after its eradication treatment, the ulcer was more minor and improved from Forrest II-c to III. This case underscores the potential for a wrong diagnosis (undiagnosed MALT-Lymphoma) if biopsy samples are not comprehensive. It also emphasizes the need for suspicion of gastric MALT-Lymphoma and the necessity of more invasive tissue biopsy, such as EUS-FNA, EMR, and ESD, when suspicion persists. Conclusion: Early diagnosis of gastric MALT lymphoma requires multiple biopsy samples during the initial endoscopy to prevent false negatives. Immunohistochemistry is essential for confirmation, and advanced techniques like EUS-FNA, EMR, or ESD play a significant role when suspicion persists. Timely H. pylori eradication can lead to ulcer healing and better outcomes. Proper endoscopist training is critical to reduce diagnostic delays.

Role of macrophage polarization in diabetic foot ulcer healing: A bibliometric study.

Diabetic foot ulcers (DFUs) are a significant contributor to disability and mortality in diabetic patients. Macrophage polarization and functional regulation are promising areas of research and show therapeutic potential in the field of DFU healing. However, the complex mechanism, the difficulty in clinical translation, and the large heterogeneity present significant challenges. Hence, this study was to comprehensively analyze the publication status and trends of studies on macrophage polarization and DFU healing. To examine the relevant literature on macrophage polarization in DFU healing. A bibliometric analysis was conducted using the Web of Science database. Relevant literature was retrieved from the Web of Science Core Collection database between 2013 to 2023 using literature visualization and analysis software (VOSviewer and CiteSpace) and bibliometric online platforms. The obtained literature was then subjected to visualization and analysis of different countries/regions, institutions, journals, authors, and keywords to reveal the research's major trends and focus. The number of publications on the role of macrophage polarization in DFU healing increased rapidly from 2013 to 2023, especially in the latter period. Chinese researchers were the most prolific in this field, with 217 publications, while American researchers had been engaged in this field for a longer period. Qian Tan of Nanjing Drum Tower Hospital and Qian Ding of Nanjing University were the first to publish in this field. Shanghai Jiao Tong University was the institution with the most publications (27). The keywords "bone marrow", "adjustment, replacement, response, tissue repair", and "activation, repair, differentiation" appeared more frequently. The study of macrophage polarization in DFU healing focused on the regulatory mechanism, gene expression, and other aspects. This study through the bibliometric method reveals the research trends and development trends in this field of macrophage polarization in DFU healing from 2013 to 2023 in the Web of Science Core Collection database. The key hotspots in this field mainly include the regulation of macrophage activation, gene expression, wound tissue repair, and new wound materials. This study provides references for future research directions.

Use of Omeprazole in A Junction to Band-Ligation for Portal Hypertensive Patients in Al-Managel Hospital 2024, Sudan

Portal hypertensive patients candidate for Band ligation were administered Omeprazole tab (proton pump Inhibitor) in Al-Managel Hospital to assess post-ligation ulcer healing and Heartburn, dysphagia and odynophagia Symptoms following ligation. Forty-five patients were treated with Omeprazole tab 20 mg twice daily for one week immediately after the ligation session and rechecked in the next session (3-4) weeks later. Healing of post-banding ulcers occurs naturally without significant association with using Omeprazole, as examined by Qui Square and Fisher's exact test. Omeprazole is significantly associated with decreased heartburn and odynophagia symptoms as checked by an Independent Paired T-test. Adjunctive use of Omeprazole with Band ligation for Portal Hypertensive patients is recommended to improve post-ligation symptoms of heartburn and odynophagia.

Novel insights into the role of gut microbiota and its metabolites in diabetic chronic wounds.

Wounds in patients with diabetes present significant physical and economic challenges due to impaired healing and prolonged inflammation, exacerbated by complex interactions between microbes. Especially, the development and healing of diabetic foot ulcers (DFUs) remain an urgent clinical problem. The human gut harbors a vast microbial ecosystem comprising intestinal flora and their metabolic products. Recent advancements in research have illuminated the concept of the "gut-skin axis," revealing intricate relationships between gut microbiota, microbiota-derived metabolites, and various skin diseases, including DFUs. This review aims to unravel the formation and healing process of DFUs in the context of the gut-skin axis. We reviewed the current research progress worldwide regarding to the gut-skin axis, compared and discussed significant changes in the microbiota colonizing the skin and gut in patients with DFUs. The roles of microbiota-derived metabolites such as lipopolysaccharides, short-chain fatty acids, and trimethylamine-N-oxide in the development of DFUs are highlighted. We also reviewed treatment strategies currently employed in clinical practice and identified potential therapeutic targets such as probiotics for treating DFUs. The need for more comprehensive experimental designs to elucidate the intricate relationship between gut microbiota and its metabolites in the context of DFUs are therefore highlighted.

Relationship between ferroptosis and healing of diabetic foot ulcer: a prospective clinical study

ObjectiveDiabetic foot ulcer (DFU) is one of the common complications in patients with diabetes mellitus (DM). In order to find a method to monitor and treat the refractory DFU, the ferroptosis level in DFU and traumatic wounds (TW) was monitored and the difference between them was analyzed. At the same time, this study further analyzed the correlation of ferroptosis levels with DM severity and DFU’s healing.MethodsA prospective cohort study was from January, 2021 to December, 2023 in the Second People’s Hospital of Gansu province, which included 59 patients with DFU and 42 patients with TW. We then used the kit to detect the indicators related to ferroptosis, including 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA) and reactive oxygen species (ROS), in the wound exudate of the two groups of patients.ResultsThe DFU group had higher ferroptosis level than the TW group (4-HNE: P = 0.003, MDA: P<0.001, ROS: P<0.001). The severity of diabetes was significantly associated with ferroptosis level in DFU patients(r = 0.936, P <0.001). The results of multiple regression analysis showed that 4-HNE (β = -0.182, P = 0.008), MDA (β = -0.478, P <0.001) and ROS (β = -0.394, P<0.001) significantly negatively predicted the healing rate of DFU.ConclusionAs a new monitoring and therapeutic target, ferroptosis level plays an important role in predicting the healing rate of DFU and assisting clinical treatment decision-making.

Effectiveness and safety of topical autologous platelet-rich fibrin membrane with total contact cast versus perilesional injectable autologous platelet-rich plasma therapy with total contact cast in trophic ulcer due to leprosy: A randomised controlled trial

Introduction With a vision of a 90% reduction of grade 2 disability (G2D) in the Global Leprosy Strategy by 2030, the management of trophic ulcer, a common G2D, has become a priority. Autologous injectable perilesional platelet rich plasma (PRP) is first generation, whereas autologous platelet rich fibrin membrane (PRFM) is second generation platelet concentrate helping in trophic ulcer healing by providing growth factors and cytokines. PRFM requires less amount of blood (8 mL) against 20 mL in PRP. Objective Evaluate the effectiveness and safety of PRFM with total contact cast versus PRP with total contact cast in leprosy trophic ulcer. Methods Observer-blind, non-inferiority randomised controlled trial recruited clinically diagnosed leprosy trophic ulcer with wound area measurement <40 cm2 after obtaining informed consent. Calculated sample size was 26 per group considering the percentage success in the control group (PRP) 39.29% and the experimental group (PRFM) 55.55%, 5% significance-level, 80% power, non-inferiority limit 10%, and 10% drop-out rate. Randomisation was done by computer generated random number table and allocation concealment by sequentially numbered opaque sealed envelope (SNOSE) technique. PRP was prepared with first spin 1,600 rpm for 10 minutes and second spin 4,000 rpm for 10 minutes. PRFM was prepared by centrifugation at 2,600 rpm for 3 minutes. Four treatment sessions followed by two follow-ups at 2 weekly intervals were conducted. Result Baseline clinico-demographic profile was similar in both groups. The surface area was significantly reduced (Friedman’s ANOVA P<0.001) in both PRP (from 422.48+657.30 sq cm to 247.84+635.96 sq cm) and PRFM (290.04+281.42 sq cm to 152.77+336.09 sq cm) with significant reduction from first FU onwards in both groups (Post-Hoc Dunn’s test P<0.001). Complete improvement was noted in 12% of PRP and 23% of PRFM (Fischer’s test P=0.465). Both groups showed improvement in DLQI. Limitation Short duration of treatment and follow-up (10 weeks). Conclusion PRFM with total contact cast is not inferior to PRP. Because of operational ease (less blood, less time), PRFM is a better alternative to PRP.

Ultrasound-Triggered Oxygen Release System for Accelerating Wound Healing of Diabetic Foot Ulcers.

Diabetic foot ulcer (DFU) is a common complication of chronic diabetes mellitus. Oxygen plays a critical role in the healing process of DFU wounds by promoting cell migration and neovascularization. However, clinical hyperbaric oxygen (HBO) therapy predominantly uses systemic oxygen administration, posing challenges in inadequate DFU local oxygen penetration and potential ectopic organs oxygen toxicity. To address these challenges, a strategy to encapsulate oxygen with lipid microbubbles (OMBs) and incorporate them into a body temperature-sensitive heparin-pluronic copolymer hydrogel (HP/OMBs) have been developed. HP/OMBs showed high biocompatibility both in vitro and in vivo. After in situ administration, oxygen can be released from HP/OMBs to the local deep site of the DFU wounds under ultrasound (US) triggering. Thus, given its biocompatibility and practicality, the combined action of HP/OMBs and the US has important translational value in accelerating diabetic chronic wound healing.

Diabetic foot ulcer photography study: a study within a trial to assess the reliability of two-dimensional (2D) photography for the assessment of ulcer healing in patients with diabetes-related foot ulcers—protocol paper

BackgroundThe primary endpoint in diabetes-related foot ulcer (DFU) trials is often time to healing, defined as complete re-epithelialisation with absence of drainage, requiring clinical expert assessment as the gold standard....

Placenta-derived biomaterials vs. standard care in chronic diabetic foot ulcer healing: A systematic review and meta-analysis.

This study explored the effectiveness of current placenta-derived biomaterials therapies in ulcer healing in DFU compared to standard of care (SOC). The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. Twelve randomized controlled trials (RCTs) with a total of 833 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving placenta-derived biomaterials therapies (OR=6.247 [4.425, 8.819], p<0.01, I2=41%) compared to control groups. Placenta-derived biomaterials therapies have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in DFU. The utilization of placenta-derived biomaterials in therapies for wound healing, particularly in chronic DFU, presents promising implications for clinical practice. These biomaterials offer a rich source of growth factors, cytokines, and extracellular matrix components, which can stimulate tissue regeneration and angiogenesis. Incorporating such therapies into clinical practice holds the potential to accelerate wound closure, reduce infection rates, and improve overall healing outcomes in people with diabetic chronic foot ulcers. Furthermore, the availability of these biomaterials can offer clinicians a readily-accessible and cost-effective alternative to traditional wound care approaches, ultimately enhancing patient care and quality of life. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Outcomes Associated With Wound Care Nurses' Practice for the Management of Venous Leg Ulcers: A Scoping Review.

The role of the wound care nurse is identified as a key element in the management of patients with venous leg ulcers (VLUs). However, the literature offers fragmented knowledge of the outcomes associated with their practice. To identify, summarize, and map all available evidence based on the wound care nurses practice for the treatment of VLUs. A scoping review was conducted in May 2024 on PubMed, CINAHL, Scopus, and Cochrane Library databases. Observational or experimental studies related to patients affected by VLUs and cared for by wound care nurse specialists were included. Of the 1562 articles reviewed, 9 studies met the inclusion criteria. The most frequently measured outcomes were clinical responses and included healing rate and ulcer recurrence. Less frequent outcomes were patient-reported and resource utilization measures. This review indicates a general predominance of outcomes related to objective clinical responses. Future studies should broaden the types of outcomes by also including patient-reported parameters (eg, pain, quality of life, stress) in order to gain greater evidence on the impact of wound care nurse specialists in the care of patients affected by VLUs.

Pharmacological investigation of selected 1,2,4 triazole derivative against ethanol induced gastric ulcer.

The present study aims to assess the therapeutic potential of (2S,3S,4S,5S,6S-2-(acetoxymethyl)-6-(4-chlorophenyl)-3-(pyridine-4-yl)5-thioxo-4,5-dihydro-1,2,4-triazol-1-yl tetrahydro-2H-pyran 3,4,5tryltriacetate (JAK05) on gastric ulcer. The current study was designed to evaluate the anti-ulcer potential of JAK05 against ethanol-induced gastric ulcer by employing in silico, in vitro and in vivo techniques. In silico studies, JAK05 has a binding score ranging from -8.51 to -21.38 (kcal/mol). Molecular dynamics simulation at 100ns shows better structural stability, stable binding affinity and stable conformation when bonded to H+/K+-ATPase. In vitro study demonstrates that JAK05 inhibits Helicobactor pylori. In vivo study confirmed that JAK05 promotes ulcer healing in rats at a dose of 40mg/kg and demonstrated a protective effect on the gastric mucosa, comparable to omeprazole by modulating acid secretion and fluid volume. Glutathione, glutathione-s-transferase and catalase levels increased in rat stomach tissue while nitric oxide decreased with the administration of JAK05. Additionally, lipid peroxide levels were found to have significantly decreased. Pathological histopathology analysis shows improved tissue structure and reduced inflammatory markers. These findings were confirmed using immunohistochemistry and enzyme-linked immunosorbent assay. JAK05 exhibits a high affinity for selected targets. JAK05 shows anti-ulcer properties by targeting through multiple mechanisms inhibiting H. pylori, reducing oxidative stress, suppressing inflammation and blocking acid production.

A case report on ulcer healing properties of aqueous solution of geranium maculatum mother tincture in chronic neuropathic ulcer of foot

A case report on ulcer healing properties of aqueous solution of geranium maculatum mother tincture in chronic neuropathic ulcer of foot

TNF-α Expression and Plasma Cell and Macrophage Numbers in Traumatic Ulcers in a Rat Model Treated by Topical or Systemic Probiotic L. casei Shirota.

Introduction: Live microorganisms, named probiotics, can improve overall physical well-being, particularly the oral cavity's health. L. casei Shirota, a popular probiotic, can influence the immune response by increasing the number of macrophages and plasma cells that play a role in traumatic ulcer healing. Aims: To determine the expression of tumor necrosis factor-alpha (TNF-α) and the varied number of plasma cells and macrophages on a traumatic ulcer animal model treated with topical or systemic administration of a probiotic L. casei Shirota. Material and Methods: Thirty-six healthy, 2-3-month-old male Rattus norvegicus weighing 175-250 gram, were designed into control and topical and systemic administration probiotic groups. The control group was treated with Aquadest 20 uL/20 gr, while topical probiotic and systemic administration probiotic groups were treated with 10,9x107 cells/kg, respectively. A heated round burnisher tip was used to traumatize the inferior incisive fornix labial area. After 3 or 7 days, the animal models were terminated. Immunohistochemical examination, Hematoxylin eosin staining, and statistical analysis were performed to analyze the expression of TNF-α and the number of plasma cells and macrophages. Results: The Mann-Whitney and Tukey HSD tests indicated significant differences (p < 0.05) in the results for the three groups. It was observed that topical administration provides more remarkable results than systemic administration for the expression of TNF-α, the number of plasma cells, and the number of macrophages. Conclusion: Topical administration of L. casei Shirota demonstrates better results than systemic administration for healing traumatic ulcers.

Evaluation of Moringa Oleifera Leaf Extract for its In vitro Antibacterial Properties, Mechanism of Action, and In vivo Corneal Ulcer Healing Effects in Rabbits' Eyes.

M. oleifera is the most adapted tree species in different medicinal eco-systems and has resilience against climate changes. This multiple-use tree provides healthy foods, snacks, honey, and fuel. Besides this, it has immense promising applications by offering antimicrobial and antibacterial activities for targeted uses. This validates the court of Hippocrates that let food be the medicine and medicine be the food for which moringa qualifies. The objective of this study is to assess the antioxidant properties of M. oleifera, in vitro antibacterial activity of hydro-ethanolic extract, and further investigate in vivo healing potential of M. oleifera for corneal ulcers and in silico analysis. To evaluate the antioxidant and in vitro antibacterial potency of the hydro-ethanolic extract of M. oleifera on clinically isolated multidrug-resistant strains of Staphylococcus aureus using agar well diffusion assay. Furthermore, in vivo, healing response of M. oleifera extract was analysed on corneal ulcers induced in rabbit eyes infected with methicillin-resistant Staphylococcus aureus. The M. oleifera extract exhibited exponential antioxidant activity. In-vitro antibacterial activity was evaluated by agar well diffusion assay showing zone of inhibition ranging from 11.05 ± 0.36 to 20 ± 0.40 mm at concentrations of 20, 40, 80, and 160 mg/ml, whereas, in our finding, no zone of inhibition was observed below 20 mg/ml concentration, which indicated that there is threshold limit below which the antibacterial activity of M. oleifera extract is not observed. Furthermore, continuous application of 3% and 5% M. oleifera extract (eye drop) four times a day for 14 consecutive days showed a significant healing response of the eyes of rabbits with corneal ulcers. These results suggest that M. oleifera extract could be a viable alternative or in combination could be used in existing antibacterial therapies for corneal ulcers. Additionally, there is a possibility of commercial formulation of M. oleifera extract in the form of deliverable pharmaceutical products; therefore, it should be explored further.

COMPARATIVE ANALYSIS OF SUBFASCIAL ENDOSCOPIC PERFORATOR SURGERY (SEPS) AND OPEN LIGATION FOR TREATING LOWER LIMB VARICOSITIES

This study compares Subfascial Endoscopic Perforator Surgery (SEPS), a minimally invasive technique, with traditional Open Ligation for treating lower limb varicosities, a manifestation of chronic venous insufficiency (CVI) that affects quality of life through complications like ulcers, edema, and skin pigmentation. Conducted over one year at Kamineni Institute of Medical Sciences, Telangana, the study involved 50 patients divided equally between the two groups, assessing postoperative complications, hospital stay duration, symptom resolution, and varicosity recurrence. Results revealed that SEPS had significant advantages. It demonstrated superior symptom resolution, with 24% of patients achieving complete ulcer healing compared to none in the Open group. Additionally, 60% of SEPS patients experienced complete edema resolution, compared to only 20% in the Open group. SEPS also enabled faster recovery, with 88% of patients discharged within 10 days, whereas all Open group patients required stays of 11 days or longer. The complication rate was lower in SEPS (4%) compared to Open Ligation (8%), with no cases of deep vein thrombosis (DVT) or skin necrosis observed in either group. These findings align with global research, highlighting SEPS as a preferred treatment modality due to its minimally invasive nature, shorter hospital stays, and better clinical outcomes. The study underscores the need for further research, particularly in diverse populations and with long-term follow-up, to validate these findings and assess the cost-effectiveness of SEPS. Comparative studies with emerging minimally invasive techniques such as laser or radiofrequency ablation are also recommended to refine treatment protocols and enhance patient-centric care. SEPS holds promise as a standard of care for chronic venous insufficiency, offering improved recovery and reduced morbidity.

Immunohistochemical Localization of Epidermal Growth Factor Receptor in Rat Buccal Mucosa Treated with Fenugreek Leaf Oil

The lack of effective treatment for oral mucosal ulcers has motivated clinicians to search for other therapeutic techniques to improve oral ulcer healing. Applying fenugreek to an ulcer triggers the release of its anti-inflammatory components, that might reduce any superfluous inflammatory processes and accelerate wound healing. The aim of this study was to investigate the effect of fenugreek leaf oil on the ulcer associated with the expression of epidermal growth factor receptor (EGFR). A total of 24 adult male rats weighing between 350 and 450 grams and 4-6 months of age were used in this study. The experimental design included: the normal group (no ulcer), the control group (12 ulcers left without treatment to the right), and the study group (12 ulcers on the left side were healed using fenugreek oil). All rats were sacrificed on the 3rd and 7th days of the experimental study, healing durations, and biological samples were prepared for histological and immunohistochemistry analysis of EGFR. The current study exhibited that the EGFR expression increased in ulcer sites treated with fenugreek after 3 days of ulceration with significant differences in comparison with other groups. In conclusion, fenugreek oil was efficient in promoting ulcer healing by enhancing epithelization. Moreover, the positive localization of EGFR increased in the study groups treated with fenugreek oil indicating its potential activity in accelerating the healing process‎‎‎.

THE ROLE OF INTRACELLULAR SIGNALING PATHWAYS IN THE DEVELOPMENT OF LOWER EXTREMITY TROPHIC PATHOLOGY AND PECULIARITIES OF ITS REGENERATION IN TYPE 2 DIABETES (PART 2)

Introduction. In endocrinological science, the pathogenesis of trophic ulcers in soft tissues, which frequently occur and progress in patients with type 2 diabetes, remains a significant yet underexplored issue. Gaining a deeper understanding of the etiology and development of chronic trophic ulcers in the context of type 2 diabetes is crucial for advancing innovative and highly effective therapeutic approaches in the near future. The aim of this study is to investigate the role of certain “minor” signaling pathways, including hypoxia-inducible factor (HIF), Notch, and nuclear factor E2-related factor 2 (Nrf2), in the regeneration of cellular elements in soft tissue trophic ulcers observed in experimental animals and patients with type 2 diabetes. Material and methods. Based on data from modern professional literature, a study was conducted to elucidate the participation of the НIF-1, Notch and Nrf2 signaling pathways in the development of acute wounds, type 2 diabetes and, finally, the occurrence, progression, and healing of trophic ulcers during this endocrine disease. Results. It has been established that under hypoxic conditions at the initial stage of the inflammatory process during the regeneration of damaged soft tissues, an increase in the НIF-1α content is observed. The involvement of this molecular factor in the development of type 2 diabetes and the suppression of its expression level in chronic trophic ulcers against the background of type 2 diabetes were revealed. It has been demonstrated that another messenger cascade, Notch, is involved in all stages of healing of wound defects of the skin in acute wounds. At the same time, with the progression of type 2 diabetes, as well as the occurrence of chronic trophic ulcers in this endocrinological disease, the activation of this intracellular cascade was recorded. The process of regeneration and healing of damaged soft tissues of the skin was also accompanied by an increase in the content of the Nrf2. However, the development of type 2 diabetes was characterized by a decrease in the level of expression of this molecule. It is important to stress that the role of Nrf2 in the healing of trophic ulcers during type 2 diabetes remains not fully studied. Conclusion. The pathogenesis of chronic trophic ulcers in type 2 diabetes is based on disturbances in the activity of individual intracellular “minor” signaling pathways. Further study of the role of messenger cascades such as НIF-1, Notch and Nrf2 will contribute to the development of new approaches to improving the effectiveness of treatment of patients with chronic trophic ulcers of the lower extremities under type 2 diabetes.

Effectiveness of most common adjuvant wound treatments (skin substitutes, negative pressure wound therapy, hyperbaric oxygen therapy, platelet-rich plasma/fibrin, and growth factors) for the management of hard-to-heal diabetic foot ulcers: a meta-analysis of randomized controlled trials for the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome.

To assess the effects of several adjuvant therapies (AT) commonly used in the treatment of diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome. A Medline and Embase search were performed up to May 20th, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AT with placebo/standard of care (SoC), with a duration of at least 12weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, major and minor amputation, serious adverse events (SAE), and all-cause mortality. AT assessed were: growth factors (GF), Platelet-rich plasma and fibrin (PRP/F), skin substitutes (SS), negative pressure wound therapy (NPWT), and hyperbaric oxygen therapy (HBOT). Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences and 95% CIs were calculated for continuous variables. Fifty-one studies fulfilled all inclusion criteria (3, 5, 27, 8, and 8 with GF, PRP/F, SS, NPWT, and HBOT, respectively). Participants treated with any of the explored AT had a significantly higher ulcer healing rate (MH-OR ranging from 2.17 to 4.18) and shorter time-to-healing in comparison with SoC/placebo. Only PRP/F and HBOT showed a significantly lower risk of major amputation (MH-OR: 0.32(0.11;0,93; p = 0.04 and 0.28(0.10;0,79; p = 0.02, respectively), despite a higher risk of SAE. No other significant effects on the above-reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as "high" for all the AT, except for NPWT ("moderate"). In conclusion, AT can actively promote wound healing and shorten time-to-healing in patients with DFU. HBOT and PRP/F also showed a reduction of the risk of major amputation, despite a higher rate of SAE.

Effectiveness of Surgical Interventions in Chronic Venous Insufficiency: An Evidence-Based Systematic Review

Chronic Venous Insufficiency (CVI) is a disease that can significantly affect patients' quality of life. Although modern surgical therapies such as endovenous thermal ablation (ETA), iliac vein stenting, and others have been introduced, the effectiveness and safety of each procedure needs to be further evaluated. This study aims to evaluate the effectiveness and safety of modern surgical interventions in the management of CVI, focusing on clinical outcomes such as ulcer healing, pain reduction, and improvement in patient quality of life. This systematic review was conducted following PRISMA guidelines by screening literature from PubMed, ScienceDirect, Google Scholar, and Cochrane Library between 2014 and 2024. Of the 17,500 articles identified, 10 studies were included through a rigorous selection process. Analysis was performed based on study design, population, intervention type, clinical outcomes, and safety profile. Endovenous thermal ablation showed an anatomical success rate of more than 96% with long-term clinical benefits. Iliac vein stenting significantly improved symptoms of deep vein obstruction (VAS: 9 to 2.5) with a primary patency rate of 92%. Methods such as mechanochemical ablation (MOCA) and cyanoacrylate embolization (CAE) offer minimally invasive approaches with low complication rates and fast recovery times. The combination of early ablation and compression therapy accelerates healing of chronic venous ulcers (median healing time: 56 vs. 82 days). Modern surgical interventions are proven effective and safe in the management of CVI, with thermal ablation as the gold standard and iliac vein stenting as the superior option for deep vein obstruction. This evidence-based approach provides important guidance for personalizing CVI therapy in the future. Further research is needed to evaluate long-term sustainability and to optimize evidence-based clinical guidelines.

Suppression of TRIM72-mediated endoplasmic reticulum stress facilitates FOXM1 promotion of diabetic ulcer healing.

Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif-containing protein 72 (TRIM72)-mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5'-monophosphate-activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1-overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72-mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers.