The effect of hyperbaric oxygen therapy on hematological indices and biochemical parameters in patients with diabetic foot.

BACKGROUND: Diabetes Mellitus (DM) is a metabolic disease with a high morbidity and mortality and increasing in prevalence all over the world. Due to the hypoxic, ischemic, inflammatory, and infective environment in DM, diabetic foot ulcers have been treated with medico-surgical interventions and adjuvant hyperbaric oxygen Therapy (HBOT). The purpose of this study was to evaluate the effects of HBOT on hematological indices and biochemical parameters in patients with diabetic foot. METHODS: The study group was formed from the file records of 103 male patients who applied to Yunus Emre State Hospital HBOT Center between September 1, 2016 and December 31, 2020, and were treated HBOT with a multidisciplinary approach. RESULTS: There were negative low correlations between number of HBOT sessions and Mean Corpuscular Hemoglobin (MCH) (P = .037, r = -0.207) and Blood Urea Nitrogen (BUN) (P = .037, r = -0.222). White Blood Cell Count (WBC), Neutrophils (NEU), Monocytes (MON), Platelet Count (PLT), and Plateletcrit (PTC) parameters were found to be decreased, and an increase in lymphocytes (LYM), Eosinophils (EOS), Mean Corpuscular Hemoglobin Concentration (MCHC), and Red Cell Distribution Width (RDW) parameters were detected after the treatments (P < .05). Again, after the treatment, glucose (Glu), C-Reactive Protein (CRP), direct bilirubin, and total protein (TP) levels were decreased, and uric acid (UA) levels increased (P < .05). CONCLUSION: HBOT improved hematological indices in patients and had a beneficial effect on biochemical parameters, particularly Glu and CRP levels. Adjuvant HBOT alleviates diabetic inflammation and has a beneficial effect on diabetic patient treatment.

Luminal Delivery of Pectin-Modified Oxygen Microbubbles Mitigates Rodent Experimental Intestinal Ischemia.

INTRODUCTION: Ischemic gut injury is common in the intensive care unit, impairs gut barrier function, and contributes to multiorgan dysfunction. One novel intervention to mitigate ischemic gut injury is the direct luminal delivery of oxygen microbubbles (OMB). Formulations of OMB can be modified to control the rate of oxygen delivery. This project examined whether luminal delivery of pectin-modified OMB (OMBp5) can reduce ischemic gut injury in a rodent model. METHODS: The OMBp5 formulation was adapted to improve delivery of oxygen along the length of small intestine. Adult Sprague-Dawley rats (n = 24) were randomly allocated to three groups: sham-surgery (SS), intestinal ischemia (II), and intestinal ischemia plus luminal delivery of OMBp5 (II + O). Ischemia-reperfusion injury was induced by superior mesenteric artery occlusion for 45 min followed by reperfusion for 30 min. Outcome data included macroscopic score of mucosal injury, the histological score of gut injury, and plasma biomarkers of intestinal injury. RESULTS: Macroscopic, microscopic data, and intestinal injury biomarker results demonstrated minimal intestinal damage in the SS group and constant damage in the II group. II + O group had a significantly improved macroscopic score throughout the gut mucosa (P = 0.04) than the II. The mean histological score of gut injury for the II + O group was significantly improved on the II group (P ≤ 0.01) in the proximal intestine only, within 30 cm of delivery. No differences were observed in plasma biomarkers of intestinal injury following OMBp5 treatment. CONCLUSIONS: This proof-of-concept study has demonstrated that luminal OMBp5 decreases ischemic injury to the proximal small intestine. There is a need to improve oxygen delivery over the full length of the intestine. These findings support further studies with clinically relevant end points, such as systemic inflammation and vital organ dysfunction.

Pharmacotherapy and revascularization strategies of peripheral artery disease.

The global epidemiological transition of atherosclerotic vascular diseases is witnessing a rapid redistribution of its burden, shifting from high-income to low- and middle-income countries. With a wide clinical spectrum, spanning from intermittent claudication to more complex critical limb threatening ischemia, nonhealing ulcers, gangrene as well as acute limb ischemia, peripheral artery disease is often faced with the challenges of under-diagnosis and under-treatment despite its high prevalence. The management of peripheral arterial disease in patients with multiple comorbidities presents a formidable challenge and remains a pressing global health concern. In this review, we aim to provide an in-depth overview of the pathophysiology of peripheral artery disease and explore evidence-based management strategies encompassing pharmacological, lifestyle, interventional, and surgical approaches. By addressing these challenges, the review contributes to a better understanding of the evolving landscape of peripheral artery disease, offering insights into effective and holistic management strategies.

The impact of ischemic vascular stenosis on LIPU hyperthermia efficacy investigated Based on in vivo rabbit limb ischemia model.

Ischemic diseases due to arterial stenosis or occlusion are common and can have serious consequences if untreated. Therapeutic ultrasound like high-intensity focused ultrasound (HIFU) ablates tissues while low-intensity pulsed ultrasound (LIPU) promotes healing at relatively low temperatures. However, blood vessel cooling effect and reduced flow in ischemia impact temperature distribution and ultrasonic treatment efficacy. This work established a rabbit limb ischemia model by ligating the femoral artery, measuring vascular changes and temperature rise during LIPU exposures. Results showed the artery diameter was narrowed by 46.2% and the downstream velocity was reduced by 51.3% after ligation. Finite element simulations verified that the reduced flow velocity impaired heat dissipation, enhancing LIPU-induced heating. Simulation results also suggested the temperature rise was almost related linearly to vessel diameter but decayed exponentially with the increasing flow velocity. Findings indicate that the proposed model could be used as an effectively tool to model the heating effects in ischemic tissues during LIPU treatment. This research on relating varied ischemic flow to LIPU-induced thermal effects is significant for developing safe and efficacious clinical ultrasound hyperthermia treatment protocols for the patients with ischemic diseases.

Effectiveness of Repetitive Hyperbaric Oxygen Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: Lower extremity artery disease is strongly associated with morbidity and is typically addressed through revascularization interventions. We assessed the clinical outcomes of patients with chronic limb-threatening ischemia (CLTI) without revascularization who did and did not undergo repetitive hyperbaric oxygen therapy (HBOT). METHODS: Between April 2002 and March 2017, the records of 58 patients with CLTI (Rutherford classification 4 in 19% and 5 in 81%) were evaluated retrospectively. HBOT was performed at 2.8 atm of oxygen (HBOT group). The control group included those who could not continue HBOT and historical controls. Patients in poor general health or with an indication for revascularization therapy were excluded. We examined major adverse events (MAEs) and limb salvage rates. Independent predictors and risk stratification were analyzed using a multivariate regression analysis. RESULTS: The mean age was 71±13 years. Of all patients, 67% had diabetes and 43% were undergoing hemodialysis. The mean follow-up period was 4.3±0.8 years. The overall survival rate was 84.5% and 81.0% at 1 and 3 years, respectively. The Cox regression analysis indicated that high body mass index (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76-0.97; p=0.01), well-nourished (OR: 1.21; 95% CI: 1.01-1.45), and HBOT (OR: 0.05; 95% CI: 0.01-0.26; p<0.001) independently predicted absence of MAEs. For major limb amputation, the ankle-brachial index (OR: 0.2; 95% CI: 0.05-0.86; p=0.03) and HBOT (OR: 0.04; 95% CI: 0.004-0.32; p=0.003) were independent predictors. CONCLUSIONS: Repetitive, stand-alone HBOT was associated with MAE-free survival and limb salvage in patients with CLTI.

Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury.

BACKGROUND: Ischemia/reperfusion injury is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal stromal cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy; however, their full potential in treating AKI remains unknown. METHODS: In this study, we employed an in vitro model of chemically induced ischemia using antimycin A combined with 2-deoxy-D-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow, and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential), and overall cell metabolism by metabolomics. RESULTS: Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction, and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40-50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites. CONCLUSION: Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.

DIONYSIUS trial: "Does increasing oxygen nurture your symptomatic ischaemic ulcer sufficiently?" Study protocol for an international multicentre randomised trial.

INTRODUCTION: Diabetic foot ulcers (DFUs) are a major complication of diabetes and often associated with peripheral arterial occlusive disease. Current available evidence shows hyperbaric oxygen therapy (HBOT) can reduce the risk of major amputation, but clinicians remain sceptical about the (cost-)effectiveness and feasibility of HBOT for ischaemic DFUs in clinical practice. Therefore, vascular surgeons and HBOT physicians worldwide feel a strong need for a sufficiently powered clinical trial to determine whether and how many HBOT sessions may be a (cost-)effective adjunctive treatment to ischaemic DFUs. METHODS: An international, multicentre, multi-arm multi-stage design is chosen to conduct an efficient randomised clinical trial. Patients will be randomised to receive standard care (wound treatment and surgical interventions following international guidelines) with either 0, 20, 30 or at least 40 sessions of HBOT. These sessions will comprise 90-120 min of HBOT at a pressure of 2.2-2.5 atmospheres absolute according to international standards. Based on a planned interim analysis, the best performing study arm(s) will continue. Primary end point is major amputation (ie, above ankle) rate after 12 months. Secondary end points are amputation-free survival, wound healing, health-related quality of life and cost-effectiveness. ETHICS AND DISSEMINATION: All patients enrolled in this trial will receive maximum vascular, endovascular or conservative treatment and local wound care according to best practice and (inter)national guidelines. HBOT therapy is added to the standard treatment and is regarded as a low-risk to moderate-risk therapy. The study is approved by the medical ethics committee of the Amsterdam University Medical Centers, location University of Amsterdam. TRIAL REGISTRATION NUMBER: 2020-000449-15, NL9152, NCT05804097.

The Impact of Controlled Physical Training with Hydrotherapy on Changes in Swelling and Claudication Distance in Patients with Atherosclerotic Ischemia of the Lower Limbs.

BACKGROUND: Patients with peripheral artery disease (PAD) often experience intermittent claudication. It is manifested by pain typically seen in the distal part of the legs during walking, which impairs the ability to walk, limits physical activity and results in lower health-related quality of life. It often leads to chronic ischemic pain, ulceration and even amputation. The aim of the study was to evaluate the effect of controlled physical training and whirlpool massage on changes in circuits, range of motion and distance of claudication in people with atherosclerotic ischemia of the lower limbs. MATERIAL AND METHODS: The study included 100 patients, males and females aged 39 to 79 years, with peripheral circulation disorders of the lower limbs. The subjects were randomly divided into two groups. Group I (G) was treated with a series of 10 lower-limb whirling massages and took part in individually planned training, including breathing, relaxation and active free lower-limb exercises. Group II-control group (GC) took part only in individually planned training. Prior to the treatment procedures and after their completion, the ranges of movement of the ankle joint and the circumference of the lower limbs were measured and the corridor test (6MWT, six-minute walk test) was performed. RESULTS: Statistically significant reduction in the circumference of the foot, ankle, calf and thigh in the G group was noticed. Both, in G and in GC group, a statistically significant increase in the range of dorsiflexion of the foot was found in comparison to the period before the procedures (p = 0.010; p = 0.006, respectively). There was also a statistically significant increase in the range of motion of the plantar flexion of the foot after the procedures in G (p = 0.007) and in GC (p = 0.048). Differences in the circumference of the lower limbs and the range of ankle joint movements between the study group and the control group before and after the therapy were not statistically significant. However, there was a statistically significant difference between these groups after the procedures in the 6-min walk test-significantly higher values of 6MWT were recorded in group G (p = 0.003). CONCLUSIONS: Individually planned training, supplemented with hydrotherapy as thermal therapy, has a beneficial effect on reducing swelling of the lower limbs, increasing the range of foot movements and extending the distance in the 6-min walk test.

Hyperbaric oxygen therapy for treatment of a late presenting ischaemic complication from hyaluronic acid cosmetic filler injection.

Vascular compromise and resulting ischaemic injury are known rare complications of cosmetic filler injections. Most hyaluronic acid vascular compromises present early and can be treated effectively by hyaluronidase. Here we present a case of ischaemic wound and mucosal necrosis after cosmetic facial hyaluronic acid injection that appeared within hours of injection but was not diagnosed and treated for 5 days. At day 5, the patient was treated with hyaluronidase injection immediately followed by 14 sessions of daily hyperbaric oxygen therapy (HBOT). Despite the delayed treatment, the patient had essentially complete recovery and the hyperbaric therapy was overall well-tolerated. Our case report suggests that hyaluronidase injection with concurrent daily HBOT sessions may be effective to allow recovery from late-presenting filler ischaemic complication. Furthermore, given the safety profile of HBOT, we suggest a more deliberate approach to this modality as a therapeutic adjunct by cosmetic practitioners when similar complications arise.

A Ternary Synergistic eNOS Gene Delivery System Based on Calcium Ion and L-Arginine for Accelerating Angiogenesis by Maximizing NO Production.

Purpose: This study aimed to construct a delivery system based on L-arginine-modified calcium phosphate (CaP) to load eNOS plasmids (peNOS), which could amply nitric oxide (NO) to repair endothelial damage, promote angiogenic activities and alleviate inflammation. Methods: pDNA-loaded CaP nanocomplex (CaP/pDNA) were prepared by co-precipitation method, subsequently modified by L-arginine. The gene transfection efficiency, pro-angiogenic and anti-inflammatory ability were investigated in vivo and in vitro. The therapeutic effect on ischemic hindlimb in vivo was assessed. Results: L-arginine modification augmented the transfection efficiency of CaP/peNOS to elevate the eNOS expression, and then served as NO substrate catalyzed by eNOS. At the same time, calcium ions produced by degradation of CaP carriers enhanced the activity of eNOS. In vitro experiments, the loading capability and transfection performance of R(L)-CaP were confirmed to be superior to that of CaP. Additionally, HUVECs treated with R(L)-CaP/peNOS showed the strongest NO release, cell migration, tube formation and the lowest inflammatory levels compared to the CaP/peNOS and R(D)-CaP/peNOS groups. We also demonstrated the advantages of R(L)-CaP/peNOS in increasing blood reperfusion in hindlimb ischemia mice by accelerating angiogenesis and reducing inflammation, which can be attributed to the highest eNOS-derived NO production. Conclusion: The combination strategy of peNOS transfection, L-arginine supplement and calcium ions addition is a promising therapeutic approach for certain vascular diseases, based on the synergistic NO production.

The role of hyperbaric oxygen for acute traumatic ischemias.

Acute traumatic ischemias are an array of disorders that range from crush injuries to compartment syndromes, from burns to frostbite and from threatened flaps to compromised reimplantations. Two unifying components common to these conditions are a history of trauma be it physical, thermal, or surgical coupled with ischemia to the traumatized tissues. Their pathophysiology resolves around the self-perpetuating cycle of edema and ischemia, and their severity represents a spectrum from mild, almost non-existent, to tissue death. Since ischemia is a fundamental component of the traumatic ischemias and hypoxia is a consequence of ischemia, hyperbaric oxygen is a logical intervention for those conditions where tissue survival, infection control and healing is at risk. Unfortunately, even with mechanisms of hyperbaric oxygen that strongly support its usefulness in traumatic ischemias coupled with supportive clinical data, clinicians are disinclined to utilize it for these conditions. This focuses on the orthopedic aspects of the traumatic ischemias, namely crush injury and compartment syndrome, and show how hyperbaric oxygen treatments can mitigate their severity.

A Composite Deferoxamine/Black Phosphorus Nanosheet/Gelatin Hydrogel Scaffold for Ischemic Tibial Bone Repair.

Introduction: Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization. Methods: In this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo. Results: The resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway. Conclusion: The BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.

Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial).

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.

Transcutaneous Electric Nerve Stimulation on ischemic rest pain in inpatients: randomised trial.

OBJECTIVE: To investigate the efficacy of a short-term application of Transcutaneous Electric Nerve Stimulation to relieve rest pain in patients with chronic limb-threatening ischemia. METHODS: In patients ³18 years old, with chronic limb-threatening ischemia and rest pain ³3 in the Visual Analogue Scale, without diabetic neuropathy were randomly assigned to 1) Transcutaneous Electric Nerve Stimulation (100 Hz, 200 µs) or 2) sham intervention, both during one or two 20 min treatment sessions. The primary outcome was pain intensity, assessed by the visual analogue scale (0-10 cm) and described by the McGill Pain Questionnaire. We used a t-test for difference of means. RESULTS: A total of 169 patients were assessed, 23 met the study criteria and were randomized. Thirty-four applications were performed in two days: in the 17 Transcutaneous Nerve Stimulation and 17 sham. The within-group analysis indicated a pain decrease in both groups (Transcutaneous Electric Nerve Stimulation, from 7-3.9 cm, p<0.0001, and sham from 5.8-3.2 cm, p<0.0001). No statistically significant difference was verified between-groups (p=0.5). CONCLUSIONS: Both groups showed a decrease in rest pain of 54 and 55%, respectively. However, there was no difference between short-term high-frequency Transcutaneous Electric Nerve Stimulation and sham intervention to relieve ischemic rest pain in chronic limb-threatening ischemia patients.

Hyperbaric oxygen treatment for intrauterine limb ischaemia: a newborn in the chamber.

Intrauterine limb ischaemia is a rare condition that may have devastating results. Various treatments are reported in the literature; however, results are not always promising and amputations may be required for some patients. Post-natal hyperbaric oxygen treatment (HBOT) may be a useful treatment option for the salvage of affected limbs. A patient who was born with total brachial artery occlusion and severe limb ischaemia was referred for HBOT. The patient underwent the first HBOT session at her 48th hour of life. A total of 47 HBOT sessions were completed (243.1 kPa [2.4 atmospheres absolute], duration 115 minutes being: 15 minutes of compression; three 25-minute oxygen periods separated by five-minute air breaks; and 15 minutes of decompression), four in the first 24 hours. Full recovery was achieved with this intense HBOT schedule combined with anticoagulation, fasciotomy and supportive care. The new-born tolerated HBOT well and no complications or side effects occurred. To the best of our knowledge, our patient is one of the youngest patients reported to undergo HBOT.

Hirudotherapy for neonatal limb ischemia during ECMO support: A word of caution.

INTRODUCTION: Disordered coagulation, clot formation and distal limb ischemia are complications of extracorporeal membrane oxygenation (ECMO) with significant morbidity and mortality. Medicinal leech therapy (hirudotherapy) has been attempted in plastic and orthopedic surgeries to improve venous congestion and salvage ischemic flaps. To our knowledge this has not been reported in pediatric cardiac surgery or during ECMO support. We present a complex neonate whose ECMO course was complicated by distal limb ischemia for whom leech therapy was attempted. PATIENT AND INTERVENTION: A 2-week-old 2.7 kg infant required ECMO support secondary to perioperative multiorgan system dysfunction following repair of critical coarctation and ventricular septal defect. Despite systemic anticoagulation, his clinical course was complicated by arterial thrombus, vasopressor-induced vascular spasm and bilateral distal limb ischemia. Medicinal leech therapy was tried after initially failing conventional measures. RESULT: Following the third leech application, this patient developed significant hemorrhage from the web space adjacent to the left great toe. An estimated 450 ml of blood loss occurred and more than 300 ml of blood product transfusions were required. He ultimately progressed to irreversible systemic end organ dysfunction and comfort care was provided. CONCLUSION: The use of medicinal leech therapy in pediatric cardiac surgery may be considered to minimize the consequences of advanced limb ischemia and venous congestion. However, this should be used with caution while patients are systemically anticoagulated during ECMO support. A directed review is presented here to assist in determining optimal application and potential course of therapy.

Comparison of the efficacy of multiple antioxidant and hyperbaric oxygen treatments in the prevention of ischemia and necrosis of local random McFarlane skin flap.

OBJECTIVE: The aim of this study was to compare the efficacy of multiple antioxidant (Proxeed Plus (PP) with Carnitine, Selenium, Zinc, Coenzyme Q10, Vitamin C, Folic Acid, Vitamin B12) on local random skin flap healing with the hyperbaric oxygen (HBO) therapy. METHODS: Fourty rats were equally divided into five groups (Control, PP, HBO, HBO + PP, PP + HBO + PP). Local random McFarlane skin flap was applied to all rats. Following the applications, evaluations were made biochemical (TAS, TOS, OSI, IL-1ß, IL-6, TNF-α, TGF-ß, VEGF) and histopathological parameters. RESULTS: Necrosis percentage was found to be lower in the PP + HBO + PP group than all other groups whereas the necrosis percentages of PP and HBO groups were similar. Oxidative stress rates were significantly higher in the control group compared to the other groups whereas it was lower in the PP + HBO + PP group than all other groups. The inflammation parameters were the highest in the control group and the lowest in the PP + HBO + PP group. Growth factors were higher in the PP + HBO + PP group than all other groups. Epithelialization and wound healing were better in the HBO and PP groups than in the control group. The greatest healing, epithelialization and vascularization was seen in the PP + HBO + PP group. The histopathological findings in the PP + HBO + PP group were better in each inner region than in the other groups. CONCLUSION: Biochemical and histopathological parameters have shown that PP reduces ischemia and necrosis and increases oxygenation in flap healing by providing significant improvement thanks to the multiple molecular structures in its content.

Improving Limb Salvage for Chronic Limb-Threatening Ischemia With Spinal Cord Stimulation: A Retrospective Analysis.

INTRODUCTION: Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease (PAD). Up to a third of CLTI patients are not eligible to receive first-line treatments such as bypass surgery or endovascular interventions. Epidural spinal cord stimulation (SCS) has been used as a method to improve microcirculatory blood flow and relieve ischemic pain in CTLI patients. The aim of the study was to evaluate limb salvage, ulcer closure, and clinical changes of SCS implanted CTLI patients at 1-year follow-up. METHODS: Eligible patients had end-stage lower limb PAD unresponsive to medical therapy and not amenable to surgical reconstruction. Patients were candidates for amputation, but limb loss was not inevitable (Fontaine stage III and IV). Pain intensity and skin temperature in the ischemic area (visual analogue scale), quality of life (WHOQoL-BREF), and ankle/brachial blood pressure index (ABI) were recorded at routine follow-up visits. Data were analyzed retrospectively. RESULTS: 29 patients underwent SCS implantation at one vascular center. The minimum follow-up period was 30 months. Limb survival at 1-year follow-up was 97% (28/29) and 73% (11/15) had complete closure of limb ulcers. Pain intensity, skin temperature, and quality of life progressively improved up to 12 months after implant, with Fontaine stage III patients improving more substantially than Fontaine stage IV patients. SCS therapy did not affect ABI measurement. No complications related to the device or procedure occurred. CONCLUSIONS: SCS is a valid alternative in patients unsuitable for revascularization. The quality of results depends on both a strict selection of patients by vascular specialists and the frequency of follow-up controls. The therapy may be more beneficial in patients classified as Fontaine stage III.

Lentiviral vector-mediated expression of C3 transferase attenuates retinal ischemia and reperfusion injury in rats.

AIMS: Our previous study showed that intravitreal delivery of self-complementary AAV2 (scAAV2)-mediated exoenzyme C3 transferase (C3) can attenuate retinal ischemia/reperfusion (I/R) injury. The current study investigated the neuroprotective effects of lentivirus (LV)-mediated C3 transgene expression on rat retinal I/R injury. MAIN METHODS: The LV encoding C3 and green fluorescent protein (GFP) together (LV-C3-GFP) or GFP only (LV-GFP) was intravitreally injected to SPRAGUE-DAWLEY rats. On day 5 post-intravitreal injection, eyes were evaluated by slit-lamp examination. The GFP expression on retina was confirmed by in vivo and ex vivo assessments. RhoA GTPase expression in retina was examined by western blot. Retinal I/R injury was generated by transiently increasing intraocular pressure (110 mmHg, 90 min). Eyes were then enucleated, and retinas processed for morphological analysis and TdT-dUTP terminal nick-end labeling (TUNEL) assay. KEY FINDINGS: No obvious inflammatory reactions or surgical complications were observed after intravitreal injection of LV vectors. There was a significant decrease of total RhoA GTPase level in the retina treated with LV-C3-GFP. Compared to the blank control group, LV-C3-GFP and LV-GFP did not affect the retinal thickness, cell density in ganglion cell layer (GCL), or numbers of apoptotic cells in retinal flat-mounts. In the LV-GFP-treated retinas, I/R decreased the retinal thickness and GCL cell density and increased apoptotic retinal cell numbers. LV-C3-GFP significantly protected against all these degenerative effects of I/R. SIGNIFICANCE: This study indicated that LV-mediated C3 transgene expression exhibits neuroprotective effects on the retinal I/R injury and holds potential as a novel neuroprotective approach targeting certain retinopathies.