Ulcer Healing Rates Research Articles

Clinical and histopathological responses to bee venom phonophoresis in treating venous and diabetic ulcers: a single-blind randomized controlled trial.

Chronic venous and diabetic ulcers are hard to treat that cause patients long time of suffering as well as significant healthcare and financial costs. The conducted study was to evaluate the efficacy of bee venom (BV) phonophoresis on the healing of chronic unhealed venous and/or diabetic foot ulcers Also, to compare the healing rate of diabetic and venous ulcers. The study included 100 patients (71 males and 29 females) with an age range of 40-60 years' old who had chronic unhealed venous leg ulcers of grade I, grade II, or diabetic foot ulcers with type II diabetes mellitus. They randomly assigned into four equal groups of 25: Group A (diabetic foot ulcer study group) and group C (venous ulcer study group) who both received conservative treatment of medical ulcer care and phonophoresis with BV gel, in addition to group B (diabetic foot ulcer control group) and group D (venous ulcer control group) who both received conservative treatment of medical ulcer care and received ultrasound sessions only without BV gel. Wound surface area (WSA) and ulcer volume measurement (UVM) were used to assess the ulcer healing pre-application (P0), post-6 weeks of treatment (P1), and after 12 weeks of treatment (P2). In addition to Ki-67 immunohistochemistry was used to evaluate the cell proliferative in the granulation tissue of ulcers pre-application (P0) and after 12 weeks of treatment (P2) for all groups. This research revealed a statistical significance improvement (p ≤ 0.0) in the WSA, and UVM with no significant difference between study groups after treatment. Regarding Ki-67 immunohistochemistry showed higher post treatment values in the venous ulcer group in comparison to the diabetic foot ulcer group. Bee venom (BV) provided by phonophoresis is effective adjuvant treatment in accelerating venous and diabetic foot ulcer healing with higher proliferative effect on venous ulcer. www.ClinicalTrials.gov, identifier: NCT05285930.

Anti-inflammatory effect of hyperbaric oxygen in the treatment of peptic ulcer disease: review

OBJECTIVE: Based on the analysis of literature data, highlight the mechanisms of anti-inflammatory action of hyperbaric oxygenation (HBO) in peptic ulcer of the stomach and duodenum (PUS and D).MATERIALS AND METHODS: The subject of study was scientific publications on the use of hyperbaric oxygenation (GBT) in treatment (PUS and D). The search was carried out on the international databases Elibrary, Pub Med, Scopus, Google Scholar from 1980–2022. A total of 38 literature sources were selected, of which at least 60% were published within the last five years. RESULTS: The effectiveness of the therapeutic effect of HBO (ulcer healing rate) in PUS and D depends on the location and size of the ulcer defect on the wall of the stomach or duodenum. At the moment, there is no conclusive data on the optimal number of HBO sessions required to achieve the maximum therapeutic effect in the treatment of PUS and D. DISCUSSION: The leading link in hyperoxic sanogenesis in this pathology is the anti-inflammatory effect of hyperbaric oxygen (HBO2), which is realized by: a) through stimulation of mucocyte formation; b) through regulation of HBO2 qualitative composition of mucocyte secretion; c) by stimulating the formation of bicarbonates by additional cells and increasing the sensitivity of these cells to their endogenous stimulant -solar acid (HCl); d) through the effect of HBO2 on gastrin formation (HCl stimulant), as well as on the diffusion of HCl from the gastric lumen into its capillary network. Together, this leads to a rapid cessation of pain syndrome, which creates conditions for the elimination of dyspeptic syndrome. This is realized through the restoration of the myoelectric activity of the stomach wall and duodenum, the regulation of the myogenic tone of their walls, as well as the elimination of the violation of gastric accommodation in the conditions of HBO. CONCLUSION: The anti-inflammatory effect of HBO2 in the treatment of PUS and D allows us to consider hyperbaric oxygenation as an integral part of the treatment of ulcerative lesion of the upper gastrointestinal tract.

Comparison of outcomes following polidocanol microfoam and radiofrequency ablation of incompetent thigh great and accessory saphenous veins

BackgroundMicrofoam ablation (MFA) and radiofrequency ablation (RFA) are both approved by the Food and Drug Administration for treatment of proximal saphenous truncal veins. The objective of our study was to compare early postoperative outcomes between MFA and RFA following treatment of incompetent thigh saphenous veins. MethodsA retrospective review of a prospectively maintained database was conducted of patients who underwent treatment of incompetent great saphenous veins (GSVs) or anterior accessory saphenous veins (AASVs) in the thigh. All the patients underwent duplex ultrasound of the treated leg at 48 to 72 hours postoperatively. Patients were excluded from analysis if concomitant stab phlebectomy was performed. Demographic data, CEAP (clinical, etiologic, anatomic, pathophysiologic) class, venous clinical severity score (VCSS), and adverse events were recorded. ResultsBetween June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent venous closure for symptomatic reflux. A total of 200 consecutive thigh GSVs and ASVs treated within the study period using either MFA (n = 100) or RFA (n = 100) were identified. The patients were predominantly women (69%) with a mean age of 64 years. The preoperative CEAP classification was similar between the MFA and RFA groups. The mean preoperative VCSS was 9.4 ± 2.6 for the RFA patients and 9.9 ± 3.3 for the MFA patients. Among the RFA patients, the GSV was treated in 98% and the AASV in 2% compared with the GSV in 83% and the AASV in 17% in the MFA group (P < .001). The mean operative time was 42.4 ± 15.4 minutes in the RFA group and 33.8 ±16.9 minutes in the MFA group (P < .001). The median follow-up was 64 days for the study cohort. The mean postoperative VCSS declined to 7.3 ± 2.1 in the RFA group and 7.8 ± 2.9 in the MFA group. Complete closure occurred in 100% of the limbs after RFA and 90% after MFA (P = .005). Eight veins were partially closed and two remained patent following MFA. The incidence of superficial phlebitis was 6% and 15% (P = .06) after RFA and MFA, respectively. Overall, symptomatic relief was 90% following RFA and 89.5% following MFA. The complete ulcer healing rate for the entire cohort was 77.8%. Deep venous proximal thrombus extension (RFA, 1%; vs MFA, 4%; P = .37) and remote deep vein thrombosis (RFA, 0%; vs MFA, 2%; P = .5) showed a trend toward being higher following MFA but the difference did not reach statistical significance. All were asymptomatic and resolved with short-term anticoagulation therapy. ConclusionsMFA and RFA are both safe and effective for treating incompetent thigh saphenous veins, with excellent symptomatic relief and a low incidence of postprocedure adverse thrombotic events. RFA resulted in improved complete closure rates following initial treatment compared with MFA. The operative times were shorter with MFA. Both modalities can be used for patients with active venous ulcers with good healing rates. Longer term studies are required to characterize the durability of MFA closure for above knee truncal veins.

Early results following comparison of radiofrequency and microfoam ablation of large diameter truncal veins demonstrate high closure rates and symptomatic relief

ObjectiveEndovenous closure of truncal veins with a large diameter (LD) (≥8 mm) has been associated with higher risk of post ablation thrombus propagation into the deep venous system. Similar findings after Varithena microfoam ablation (MFA) have not been characterized. The study objective was to analyze outcomes after both radiofrequency ablation (RFA) and MFA and of LD truncal veins. MethodsA retrospective review of a prospectively maintained database was performed. All patients who underwent MFA and RFA for LD symptomatic truncal vein reflux (≥8 mm) were identified. All patients had postoperative duplex (48-72 hours) scanning. Patients underwent subsequent clinical follow-up at 3 to 6 weeks. Demographic data, CEAP Classification, Venous Clinical Severity Score, procedure details, adverse thrombotic events, and follow-up data were abstracted. ResultsBetween June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent truncal vein (great, accessory, and small saphenous) closure for symptomatic reflux. Sixty-six limbs in the MFA group met inclusion criteria. Sixty-six consecutive limbs treated with RFA during the same time period were included as a comparison group. The mean truncal vein diameter treated was 10.5 mm (RFA, 10.0 mm; MFA, 10.9 mm). Twenty-nine limbs (44%) in the RFA group underwent concomitant phlebectomy. Tributary veins were concomitantly sclerosed in 34 MFA limbs (52%). Total procedural times were shorter in the MFA group (MFA, 31.6 minutes vs RFA, 55.7 minutes) (P < .001). Immediate closure rates were 100% and 95% in the RFA and MFA groups, respectively. Venous Clinical Severity Scores improved after treatment in both groups (RFA, from 9.5 to 7.8; P ≤ .001) (MFA, from 11.3 to 9.0; P ≤ .001). In the RFA and MFA groups, 83% and 79% of venous ulcers healed during the study period, respectively. Symptomatic superficial phlebitis occurred after RFA in 11% and 17% MFA. The incidence of postablation proximal deep venous thrombus extension was 3.0% in the RFA group and 6.1% in the MFA group, which was not statistically significant. All resolved with short-term oral anticoagulant therapy. No remote deep venous thromboses or pulmonary emboli occurred in either group. ConclusionsHigh early closure rates, symptom relief and ulcer healing rates can be achieved after RFA and MFA of LD saphenous veins. Both techniques can be used safely across a wide array of CEAP classes. Longer term studies are required to characterize the durability of MFA closure and sustained symptom relief in LD truncal veins.

Fractional Epidermal Skin Grafts in Hard-to-Heal Wounds: Case Series.

Cellutome™ is a minimally invasive, automated system for harvesting fractional epidermal micrografts. This therapy is indicated for granulating, small size, poor exuding acute wounds. We enrolled 15 patients with 9 venous leg ulcers and 6 atypical ulcers. The micrografts were applied with a nonadherent dressing and covered with a polyurethane foam and multilayer bandage. We scheduled 3 weekly visits for the change of the secondary dressings and multilayer bandage and clinical assessment (Wound Bed Score [WBS], pain assessment, and healing rate). The lesions were measured with the Silhouette Star™ system, a software that allows measurement of perimeter and area from a digital image. The only symptom during the procedure was a sensation of warmth. The donor area healed in 2 weeks in all patients (n = 15). We reported an area reduction of 24.30% in typical ulcers and 38.82% in atypical ulcers after 3 weeks. The average WBS improved in all ulcers from 13.06 to 14.93. The average healing rate was 0.19 mm/day both in typical and atypical ulcers. Consequently, in our small case series fractionated epidermal graft treatment significantly promoted the healing rate in all chronic ulcers regardless of etiology. Future studies with larger case series will be needed.

Angiosome Oriented or Least Diseased Vessel, Which Is the Optimal Target Arterial Path for Endovascular Revascularisation in Patients With Diabetic Foot Ulcers?

The aims were to determine whether, when treating diabetic foot ulcers (1), selecting an angiosome directed (AD) vessel as the target arterial path (TAP) when candidate vessels have comparably severe disease impacts outcomes and (2) whether a more severely affected AD vessel or a less severely affected non-angiosome directed (NAD) vessel should be chosen. This was a retrospective observational study. Patients with diabetic foot ulcers who had undergone endovascular revascularisation in the institution between January 2016 and May 2020 and had been followed up for two years were included. Eligible patients were identified retrospectively and relevant data were collected from the institution's electronic medical records. The severity of the lesions was classified using the Global Limb Anatomic Staging System (GLASS). Outcomes between various subgroups were compared according to the severity of the lesions to determine the optimal TAP choice in each case. The study cohort comprised 215 patients (216 limbs). The affected limbs were classified as follows: 93 (43.1%) as GLASS 1 - 2 AD; 27 (12.5%) as GLASS 1 - 2 NAD, 62 (28.7%) as GLASS 3 AD, and 34 (15.7%) as GLASS 3 NAD groups. In the GLASS 1 - 2 group, rates of ulcer healing, survival, and amputation free survival were higher and time to healing shorter in the AD than NAD group. In the GLASS 3 group, there were no significant differences between the AD and NAD groups for any studied outcome measures, including ulcer healing and overall survival. Using a more severely diseased AD as the TAP did not achieve significantly better outcomes than using a less severely affected NAD vessel. Selecting the AD vessel may achieve better outcomes when two candidate TAPs belong to GLASS 1-2, whereas selecting the least diseased vessel as the TAP regardless of AD or NAD status may be preferable in other situations.

Level of 25-hydroxyvitamin D and vitamin D receptor in diabetic foot ulcer and factor associated with diabetic foot ulcers

BackgroundAt present, there is no clinical study to elucidate the correlation between vitamin D deficiency and the incidence of diabetic foot osteomyelitis (DFO).This study aims to clarify levels of 25-hydroxyvitamin D [25(OH)VD] in peripheral blood and vitamin D receptor (VDR) expression in wound margin tissues (T-VDR) of patients with type 2 diabetes mellitus (T2DM) with diabetic foot ulcer (DFU) and DFO, and to determine its correlation with treatment outcomes of DFU and DFO, and and its value as a potential biomarker for the diagnosis of DFU and DFO.Methods156 T2DM patients with DFU (DFU group), 100 T2DM patients without DFU (T2DM group), and 100 healthy controls (NC group). The DFU group patients were subdivided into DFO (n = 80) and NDFO groups (n = 76). The level of serum 25(OH)VD was measured via chemiluminescence immunoassay, and T-VDR expression level was determined by quantitative real-time PCR.ResultsThe levels of serum 25(OH)VD in the DFU group were significantly lower than the T2DM group [(10.3 (5.8, 18.7) vs 15.7 (8.6, 24.6) ng/mL, P = 0.002)]. Similarly, the levels of serum 25(OH)VD and T-VDR expression in the DFO group were statistically lower than the NDFO group [9.2 (5.2, 20.5) vs 12.8 (6.9, 22.1) ng/mL, P = 0.006)], [1.96 (0.61, 3.97) vs 3.11 (1.36, 5.11), P = 0.004)], respectively. Furthermore, the levels of serum 25(OH)VD and T-VDR expression in DFU patients were positively correlated with the ulcer healing rate of foot ulcer after 8 weeks of treatment ( P = 0.031, P = 0.016, respectively). Multivariate logistic regression analysis showed that low level of serum 25(OH)VD was an independent risk factor for DFU and DFO (ORDFU = 2.42, ORDFO = 3.05, P = 0.008, 0.001, respectively), and decreased T-VDR expression level was an independent risk factor for DFO (OR = 2.83, P = 0.004). Meanwhile, the ROC curve analysis indicated that the AUC of serum 25(OH)VD level for the diagnosis of DFU and DFO was 0.821 (95% CI, 0.754–0.886, P < 0.001) and 0.786 (95%CI, 0.643–0.867, P < 0.001), respectively. When establishing a diagnosis of DFO, the AUC of T-VDR expression level was 0.703 (95%CI: 0.618–0.853, P < 0.001).ConclusionsThe levels of serum 25(OH)VD and T-VDR expression in DFU and DFO decreased. Serum 25(OH)VD and T-VDR are potentially valuable biomarkers for diagnosis and prognosis of DFU and DFO..

Beneficial Effects of a Blended Fibroin/Aloe Gel Extract Film on the Biomolecular Mechanism(s) via the MAPK/ERK Pathway Relating to Diabetic Wound Healing.

In diabetic patients, the process of wound healing is usually delayed or impaired. A diabetic environment could be associated with dermal fibroblast dysfunction, reduced angiogenesis, the release of excessive proinflammatory cytokines, and senescence features. Alternative therapeutic treatments using natural products are highly demanded for their high potential of bioactive activity in skin repair. Two natural extracts were combined to develop fibroin/aloe gel wound dressing. Our previous studies revealed that the prepared film enhances the healing rate of diabetic foot ulcers (DFUs). Moreover, we aimed to explore its biological effects and underlying biomolecular mechanisms on normal dermal, diabetic dermal, and diabetic wound fibroblasts. Cell culture experiments showed that the γ-irradiated blended fibroin/aloe gel extract film promotes skin wound healing by enhancing cell proliferation and migration, vascular epidermal growth factor (VEGF) secretion, and cell senescence prevention. Its action was mainly linked to the activation of the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway known to regulate various cellular activities, including proliferation. Therefore, the findings of this study confirm and support our previous data. The blended fibroin/aloe gel extract film displays a biological behavior with favorable properties for delayed wound healing and can be considered as a promising therapeutic approach in the treatment of diabetic nonhealing ulcers.

Application and value of intravascular ultrasound for excimer laser ablation combined with drug-coated balloon in the treatment of lower limb arteriosclerotic obliterans

Objective: To examine the value of intravascular ultrasound (IVUS) for excimer laser ablation (ELA) combined with drug-coated balloon (DCB) in treating lower limb arteriosclerotic obliterans (ASO). Methods: As a prospective case series study, patients who underwent ELA combined with DCB for lower limb ASO with the guidance of IVUS from September 2021 to March 2022 at Department of Vascular Surgery, Zhongshan Hospital, Fudan University were enrolled prospectively. Lesion characteristics, procedure-related outcomes and complications were collected. The therapy outcomes were compared with baseline data by paired t test. Results: There were 8 males and 2 females, aged (72.0±5.9) years (range: 61 to 81 years). Of all the 11 lesions, there were 8 lesions in superficial femoral artery and 3 in popliteal artery. The lesion length was (7.0±2.4) cm (range: 3.2 to 9.8 cm). There were 4 chronic totally occlusion and 7 severe stenosis. All patients underwent the operation successfully. The technical success rate was 10/11. Bailout stenting was performed in one lesion because of flow-limiting dissection. Four lesions were grade 3 to 4 in peripheral artery calcium score system, and 9 lesions with calcification arc≥180°. Larger diameter drug-coated balloons were selected in 5 lesions after measurement of intravascular ultrasound. The follow-up time was (6.0±1.9) months (range: 3 to 9 months). The ankle-brachial index of the patient was significantly improved immediately after surgery (0.97±0.13 vs. 0.48±0.18, t=-7.60, P<0.01) and at 3 months after surgery (0.95±0.12 vs. 0.48±0.18, t=-7.17, P<0.01). The 3-month primary patency rate was 11/11, the target lesion reintervention was 0 and ulcer healing rate was 3/4. Conclusion: IVUS assisted ELA in the treatment of lower limb artery lesions is safe and effective in early stage.

Saving the foot: Simple orthopaedic surgical intervention demonstrates improved outcomes and reduced costs

BackgroundForefoot ulceration in diabetes requires significant resources, with high cost and low rates of success. The authors present the results of tendon procedures (percutaneous toe tenotomy and percutaneous tendo-achilles lengthening) under local anaesthetic to adjust mechanics in patients with diabetic neuropathic forefoot ulceration. MethodsRetrospective review of electronic patient record of 19 patients (22 feet) undergoing local anaesthetic tendon procedures between April 2019 and April 2021 with a 12 month follow up period. Size of ulcer, rate of ulcer healing, complication rates and ulcer recurrence were recorded and compared to a population of conservatively-managed patients (14 patients, 15 feet) treated prior to the introduction of tendon procedures. All clinical information obtained from electronic patient records. ResultsAll patients undergoing tendon procedures achieved complete ulcer healing at a mean time of 3.3 weeks for toe tip ulcers (after toe tenotomy) and 4.5 weeks for metatarsal head ulcers (after Achilles lengthening). There were no admissions for diabetic foot sepsis, reduced recurrence, reduced amputation rates and no mortality.Of the conservatively managed cohort, only 3 of the 15 achieved ulcer resolution without recurrence within the 12 month study period.The cohort managed conservatively had an average cost of £ 9902 per patient, per annum. The intervention cost was £ 1211 per patient, saving an average of £ 8691 per patient, per annum with ulcer resolution (88 % reduction in costs). ConclusionSignificant patient benefit, reduction in resource use and cost saving was seen with this simple intervention, which merits full evaluation in a clinical trial. Level of EvidenceLevel-IV

The Effect of Vibration on the Acceleration of Wound Healing of Diabetic Neuropathic Foot Ulcer: A Prospective Experimental Study on Human Patients.

Diabetic foot ulcers are a common complication that occurs in approximately 15 percent of patients with diabetes mellitus. Over 60% of diabetic foot ulcers are caused by underlying neuropathy. Former studies on diabetic animals with foot wounds found that vibration platforms significantly accelerate wound healing by catalyzing epithelization, promoting angiogenesis, and enhancing muscle bulk. This result suggests that there is evidence that vibrations may accelerate diabetic neuropathic ulcer healing in human patients. However, to the best of our knowledge, the effect of vibration on the enhancements of diabetic foot ulcer healing in human patients is rarely investigated. Hence, in this work, we conducted an experimental study with human subjects to investigate whether vibration therapy, as a complement to the standard wound treatment, can accelerate the wound healing rate of diabetic neuropathic foot ulcers. In this prospective experimental study, 80 participants diagnosed with Wagner grades I−III diabetic neuropathic foot ulcers were randomly distributed to experimental (n = 40) and control groups (n = 40). Patients in the intervention group received standard wound treatment and vibration wound therapy (VWT), whereas patients in the control group retrieved only standard wound treatment. The results (p = 0.024, α = 0.05) show notable differences in the median healing rate between the intervention group (25 days, 95% CI: 20.3−29.7) and control group (33 days, 95% CI: 25.6−40.4), with the effect-size r, Cohen’s d, Glass’s Δ, and Hedges’ g, respectively, being 0.810, 2.764, 2.311, and 2.772. Moreover, the nitric oxide (NO) level, wound closure area, and wound healing score after intervention significantly differed between the two groups (p < 0.05), putting the intervention group on a higher level than the control group. Furthermore, positive associations were found between the NO level and wound healing closure rates. These findings suggested that VWT enhances diabetic neuropathic foot ulcer healing in terms of healing rate, wound closure area, healing score, and elevated NO level. Considering that no clinically adverse effects were found in the patients induced with vibration intervention, VWT can be regarded as a complementary therapy to the existing ones to accelerate the healing of DFUs.

Effect of Endovenous Laser Ablation Along With Compression Therapy on Chronic Venous Ulcer Healing.

Introduction Chronic venous insufficiency is a major cause of morbidity, and there is a paucity of data regarding its epidemiology due to the lack of a central wound registry. In this study, we aimed to study the time for healing of the ulcer and compliance with compression therapy (CT) following endovenous laser ablation (EVLA) ± ultrasound-guided foam sclerotherapy (UGFS) along with CT in patients with chronic venous ulcers. Methods This prospective observational study was conducted from January 2020 to June 2021 after obtaining institutional ethical committee clearance. Patients with chronic venous ulcers (>six weeks to <six months duration) were included in this study. Demographic details, venous duplex findings, and duration of ulceration were noted. All patients underwent EVLA (Biolitec® 1470 nm) ± UGFS and CT. The patients were followed up weekly till the healing of the ulcer, followed up at one month, three months, and then at six monthly intervals to look for recurrence. Venous clinical severity score (VCSS) at presentation and follow-up, compliance with CT, rate of ulcer healing at six months, and recurrence rates at two years of follow-up were observed prospectively. Results The mean age of the study participants was 45.7±14.2 years, of which 42 (84%) were males. Ulcer size of <2 cm was present in 38%, 2-4 cmin 52%, and >4 cmin 10% of patients. A total of 38% of patients underwent only EVLA, and EVLA+UGFS were done in 62% of participants. The healing rate at six months follow-up was 92%, with the average time taken being 2.55±1.38 months. Those who remained with an unhealed ulcer at six months follow-up had anulcer size of >5 cmand an age of >50 years. Ninety-six percent of the patients were compliant with CT after an endovenous intervention. The recurrence rate at two years post-ablation was 6%. VCSS was 19.66±3.23 at presentation and 5.5±2.82 at six months of follow-up. Conclusion Endovenous ablation of superficial venous reflux along with CT is associated with a shorter healing time of venous ulcerations and reduced chances of recurrence.There is an improvement in VCSS score over the period of six months follow-up.

Dynamic characterization of vascular response and treatment in oral traumatic ulcer in mice via photoacoustic imaging.

Dynamic surveillance of vasculature is essential for evaluating the healing of oral ulcer. Existing techniques used in vascular imaging face limitations, such as inadequate spatial resolution, restricted diagnostic depth, and the necessity of exogenous contrast agents. Therefore, this study aimed to use robust photoacoustic imaging (PAI) for the dynamic monitoring of vascular response during healing and the associated treatment process of oral ulcer. Kunming mice (male, 8 weeks old, 31-41 g) were treated with 50% acetic acid for 90 s on the tongue mucosa for induction of oral traumatic ulcer. Mice were randomly divided into three groups (n=12): the control, compound chamomile and lidocaine hydrochloride gel (CCLH), and phycocyanin (PC) groups. PAI was then conducted on days 0, 2, 3, 5, and 7 to obtain vessel parameters of the ulcer area, including vessel intensity, density, mean diameter, maximum diameter, and curvature. Immunohistochemical and hematoxylin and eosin (HE) staining were performed on days 3 and 7 to assess microvessel density and inflammation score. The ulcer healing rate and body weight changes were evaluated for clinical observation. Beginning on the second day after ulcer induction, there was a progressive increase over time in blood intensity and vessel parameters, including vascular density and diameter. On day 7, the CCLH and PC groups demonstrated significantly higher measures than did the control group in terms of blood intensity (P<0.05 and P<0.01), vascular density (both P values <0.05), mean diameter (both P values <0.01), and maximum diameter (P<0.01 and P<0.05). Vessel curvature in the two treatment groups exhibited no significant differences compared to that in the control group (both P values >0.05). The effects of vascular morphological changes were further supported by the histological and clinical outcomes. On day 7, compared to that of the control group, the level of microvessel density was significantly higher in both the CCLH (P<0.01) and PC (P<0.05) groups. The histopathological score in PC group was significantly lower than that of the control group on day 7 (P<0.05). Additionally, compared to that of the control group, the healing rates of the CCLH (P<0.01) and PC groups (P<0.05) were superior on day 7. On day 3, the control group showed more weight loss than did the CCLH (P<0.05) and PC (P<0.01) groups. These findings indicate that PAI is a valuable strategy for the dynamic and quantitative analysis of vascular alterations in oral traumatic ulcers and support its prospective application in improving clinical treatment.

Association of Glycosylated Haemoglobin and Wound Healing in Diabetic Foot Ulcer: A Prospective Cohort Study

Introduction: Diabetes Mellitus (DM) is a disease that, over time, can affect practically all organ systems in the body, including the skin and circulatory systems. An estimated 15% of all diabetic patients develop a foot ulcer in their lifetime. Although it is clear from the literature review that strict glycaemic control prevents complications, the relationship between Glycosylated Haemoglobin (HbA1c) value and wound healing in diabetic foot patients is less well-defined. Aim: To determine the association between Glycosylated Haemoglobin (HbA1c) and wound healing rate in Diabetic Foot Ulcers (DFUs). Materials and Methods: This prospective cohort study was conducted in the Department of General Surgery, Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India, between August 2018 and July 2020. All patients between 18 and 70 years old, diagnosed with diabetic foot according to the World Health Organisation definition, and presenting with a lower limb ulcer were included as study participants. A detailed clinical history, examination of the patient, limb, and ulcer, and baseline HbA1c assessment were performed. The ulcer wound was graded and staged according to the University of Texas Wound classification system. All selected patients were divided into two groups. Group-A (n=15) comprised patients with HbA1c ≤7%, and Group-B (n=15) consisted of patients with HbA1c &gt;7%. The primary outcome was the wound healing rate per day in relation to HbA1c levels at baseline and subsequent followup. The secondary outcomes were the demographic profile and predisposing factors affecting the healing of DFUs. Student’s t-test (two-tailed, independent) and Chi-square/Fisher’s-exact tests were performed for statistical analysis. Results: The mean age of the subjects was 57.33±7.43 years in Group-A and 56.20±7.51 years in Group-B. There was a male preponderance in both Group-A (9) and Group-B (11). A total of 11 (36.7%) patients had a history of smoking, all of them being male. The mean healing rate per day was 0.09±0.02 cm2 /day in Group-A patients, which is higher compared to Group-B with 0.02±0.01 cm2 /day. Conclusion: Strict glycaemic control is a mainstay in preventing the progression of foot ulcers to gangrene and, therefore, amputation. A lower baseline HbA1c at the presentation of DFU is indicative of a favourable outcome in terms of wound healing, with comprehensive treatment and follow-up efforts.

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study.

The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori (H. pylori) infection status and CYP2C19 polymorphism on anaprazole. In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers. ClinicalTrials.gov, NCT04215653.

Effect of Percutaneous Endovascular Angioplasty Combined with Negative Pressure Drainage on the “One-Stop” Treatment of Ischemic Diabetic Foot Ulcer

To explore the therapeutic effect, safety, and economic benefit of a "one-stop" diagnosis and treatment mode of vascular surgery for ischemic diabetic foot (DF) ulcer and to analyze the associated and independent factors that affect ulcer healing. In a prospective, single-center study, patients with ischemic DF ulcers from January 2017 to July 2021 were treated with either percutaneous endovascular angioplasty combined with negative pressure closed drainage (PTA-VSD) or percutaneous endovascular angioplasty combined with depuration (PTA-UD). The effectiveness and economic benefits of the 2 measures were compared, and independent factors affecting ulcer healing were explored via univariate and logistic regression analyses. Fifty patients with ischemic DF ulcer (25 patients in the PTA-VSD group and 25 patients in the PTA-UD group; 40 males and 10 females) were included, with an average age of 67.74±10.71years. No difference was observed in the demographic data. The findings showed that the ulcer healing time in the PTA-VSD group was significantly shorter than that in the PTA-UD group (154.79 vs. 238.31days), and the ulcer healing rate at 180days post surgery was significantly greater in the PTA-VSD group (52% vs. 12%) (P=0.002, < 0.05). The ulcer score in the PTA-VSD group decreased significantly at 3, 6, and 12months post surgery. The duration of hospitalization in the PTA-VSD group was greater (P=0.002, <0.05), but no significant difference in hospitalization frequency and cost was observed between the 2 groups. During follow-up, there was 1 death and 1 amputation in the PTA-UD group, but no death or amputation in the PTA-VSD group. Arterial occlusion was primarily located in the femoral-popliteal artery and the inferior knee artery in the 2 groups, and PTA intervention effectively opened the outflow tract of the affected limb. Two to three outflow tracts were opened in 41 patients. The ankle-brachial index (ABI) after surgery was significantly higher in both groups than before. Univariate and multivariate logistic regression analyses revealed that the Wagner grade and number of outflow channels and therapies (PTA-VSD) could be independent factors affecting ulcer healing. The severity of DF ulcers is an important factor affecting the quality of life of patients. A multidisciplinary "one-stop" treatment strategy based on percutaneous endovascular angioplasty combined with negative pressure-sealing drainage can rapidly and effectively restore the blood flow to the affected limb and promote ulcer healing without increasing medical costs.

The Relationship Between the Global Limb Anatomic Staging System Inframalleolar Modifier and the Outcomes of Diabetic Foot Ulcer with Peripheral Artery Disease

We aimed to investigate the relationship between the condition of the inframalleolar (IM) arteries, as assessed by the Global Limb Anatomic Staging System Inframalleolar (GLASS IM) modifier, and the outcomes of patients with diabetic foot ulcers. The data of 215 patients, who underwent endovascular therapy from January 2016 to May 2020 at our center, were retrospectively reviewed. Patients were divided into the P0, P1, and P2 groups according to the angiography results. The rates of ulcer healing, limb salvage, survival, and amputation-free survival were compared during the 2-year period after discharge. Of the 216 affected limbs, 35 (16%) were classed as P0, 122 (57%) as P1, and 59 (27%) as P2. Compared with the P2 group, the P0+P1 group had a higher ulcer healing rate (P=0.001), a shorter ulcer healing time (P=0.004), and a higher survival rate (P=0.044). GLASS IM Modifier classification P2 was an independent predictor of nonhealing ulcers. No significant difference was observed between the P0 versus P1 groups. GLASS IM modifier classification P2 is an independent risk factor for a poor outcome. GLASS IM modifier classification P0 versus P1 demonstrates similar outcomes to each other.

A Comparison of Doxycycline and Amoxicillin Containing Quadruple Eradication Therapy for Treating Helicobacter pylori-Infected Duodenal Ulcers: A Multicenter, Opened, Randomized Controlled Trial in China.

Background: Increased antibiotic resistance is one of the major factors contributing to the failure of H. pylori eradication. This study aimed to compare the efficacy and safety of doxycycline and amoxicillin, both critical components for bismuth-based quadruple therapy, for the first-line treatment of H. pylori-infected duodenal ulcers. Methods: An open, randomized case-controlled, multicenter trial was conducted in seven hospitals in China. A total of 184 eligible participants were divided into an IDFB (ilaprazole 5 mg, doxycycline 100 mg, furazolidone 100 mg, and bismuth 220 mg bid) or IAFB (ilaprazole 5 mg, amoxicillin 1000 mg, furazolidone 100 mg, and bismuth 220 mg bid) group for 14 days. Both groups were administrated with ilaprazole 5 mg qd for another 14 days. The main outcome was an H. pylori eradication rate; secondary outcomes were ulcer healing, relief of symptoms, and incidence of adverse effects. Results: The H. pylori eradication rates were 85.9% (95% CI 78.6−93.9) in the IDFB vs. 84.8% (95% CI 77.3−92.3) in the IAFB group in ITT analysis (p > 0.05), and 92.9% (95% CI 87.4−98.5) vs. and 91.8% (95% CI 85.8−97.7) in PP analysis (p > 0.05). The overall ulcer healing rates of IDFB and IAFB were 79.1% and 84.7% (p > 0.05), both effective in relieving symptoms. Only nine participants had adverse reactions in this trial (4/92 in IDFB and 5/92 in IAFB). Conclusion: A bismuth quadruple regimen containing doxycycline or amoxicillin could be an effective and safe treatment for H. pylori eradication, while doxycycline replacement is an alternative for participants with penicillin allergy.

Effectiveness and safety of a newly designed self-assembling gel in the treatment of endoscopic submucosal dissection-induced gastric ulcer: A multicenter randomized controlled trial.

Objectives: To evaluate the effectiveness and safety of a newly designed self-assembling gel in treating ESD-induced gastric ulcers in patients. Methods: This open-label, multicenter, randomized controlled trial enrolled patients who underwent ESD between September 2020 and May 2021. Patients were randomized (1:1) to receive the gel (applied to cover the entire ulcer bed under endoscopic guidance immediately after ESD; gel group) or not (control group). The primary outcome was the ulcer healing rate at 28days. And the secondary outcomes were the delayed bleeding, changes in the ulcer stage, and adverse events. Results: Finally, 125 patients (mean age, 63.7years; 70 [56.0%] males) were enrolled. The ulcer healing rate was higher in the gel group than in the control group at 28days (96.9 ± 4.1% vs. 94.7 ± 5.0%; p = 0.001). The ulcer reduction rate at 28days differed significantly (p < 0.001) between ulcers with majority gel coverage (99.8%), ulcers with minority gel coverage (96.2%), and ulcers with no gel coverage (98.0%). Delayed bleeding was found in 1/63 gel-treated patients (1.6%) versus 5/62 controls (8.1%). A1-stage ulcers were found in 16/63 patients in the gel group versus 44/62 patients in the control group (25.4% vs. 71.0%, p < 0.001) at 3-5days. Conclusion: The newly developed self-assembling gel was safe and effective in accelerating gastric ulcer healing in patients after ESD. Clinical Trial Registration: UMIN Clinical Trials Registry System (registration number, ChiCTR2100052935).

The effectiveness of ozone therapy for diabetic foot treatment: A systematic review

Introduction: Diabetic foot ulcer is a local wound in patients with diabetes. Ozone therapy is becoming a treatment option as it accelerates healing. Objective: To verify the effectiveness of ozone therapy for the treatment of diabetic foot ulcers. Methodology: We performed searches in PubMed, SciELO, LILACS, MEDLINE, Web of Science and CINAHL databases until October 2021. The search included article references and clinical trial registry websites without limitation of language or publication date. Randomized and non-randomized clinical trials addressing ozone therapy in patients with diabetic foot ulcers were included. The Risk of Bias assessment tool and the Review Manager software, version 5.4 were used. Results: Six randomized and non-randomized clinical trials met the inclusion criteria (608 patients). Only two studies were considered to be at low risk of bias, with adequate randomization, allocation concealment, and blinded evaluation of results. One study compared two IPC regimens where there was evidence of a statistically significant treatment effect in favor of the rapid IPC regimen (hazard ratio 0.74, 95% CI 0.56 to 0.90). Five trials evaluated CPI as adjunctive therapy to standard therapies and agreed that CPI increases the rate of ulcer healing and a higher cure rate. Two trials evaluated CPI alone compared to other therapies. Conclusion: Ozone therapy for diabetic foot ulcers has been shown to be effective as an adjunct to standard treatment, although the included studies were classified as having a high risk of bias.