Transcutaneous Oxygen Tension Research Articles

Peripheral blood mononuclear cell transplantation to treat no-option critical limb ischaemia: effectiveness and safety.

Local intramuscular transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilised peripheral blood mononuclear cells (PB-MNC) has been shown to be effective for treating patients with no-option critical limb ischaemia (CLI) who are not considered suitable to undergo surgical bypass or percutaneous transluminal angioplasty. The aim of this study was to investigate the effectiveness and safety of PB-MNCs as a treatment for no-option CLI patients. This prospective cohort study was conducted between April 2013 and December 2017. Patients with no-option CLI were treated with G-CSF 5-10 µg/kg/day for 3 days. PB-MNCs (7.1±2.2×1010) with CD34+ cells (2.1±1.2×108) were collected by blood cell separator and then injected into the calf or thigh of ischaemic limbs. Ankle-brachial index, toe-brachial index and transcutaneous oxygen tension were recorded at 1 and 3 months after injection. The amputation rate and the wound healing rate were also recorded. Eight patients took part in the study. Two patients experienced rest pain relief 1 month after PB-MNC therapy. Five patients had healed ulcer at 6 months after PB-MNC therapy. Limb ischaemia did not improve after PB-MNC therapy in one patient. Below-knee amputation was performed in that patient due to extension of gangrene. Two patients required reinjection of PB-MNCs because of recurrence of ischaemic ulcer. The limb salvage rate after 1 year was 87.5%. Local intramuscular transplantation of G-CSF-mobilised PB-MNCs might be a safe and effective treatment for no-option CLI patients.

Analysis of biomonitoring data after full-thickness skin grafting.

Skin graft vascularization is investigated mainly by histological evaluation. Immunohistochemical analysis has been conducted only in mice. Transcutaneous oxygen tension (TcPO2 ), which is an index of blood flow, has not been evaluated in skin grafts and only a few studies have reported biologic monitoring data using color tone evaluation and surface temperature. In humans, these tests can be performed non-invasively. To evaluate human skin graft vascularization, we analyzed biomonitoring data after skin grafting. We evaluated 14 patients who underwent skin grafting surgery at Nagoya City University Hospital. The TcPO2 , color tone, surface temperature, and dermoscopic observations at recipient sites were measured at postoperative day (POD) 4, 6, and 11. Mean TcPO2 levels at POD4, 6, and 11 were 12.7, 15.2, and 33.5mmHg, respectively, and significantly higher at POD11 than at POD4 (p=0.003, Steel-Dwass test). Dermoscopic observation revealed gradually increasing redness and yellowness. Color tone evaluation measured by spectrophotometry supported the appearance. The a*(redness) value at POD4, 6, and 11 was 6.19, 9.20, and 11.27, respectively, and significantly higher at POD11 than at POD4 (p<0.001, Steel-Dwass test). The b*(yellowness) value at POD4, 6, and 11 was 8.83, 9.24, and 13.02, respectively, and significantly higher at POD11 than at POD4 (p=0.020, Steel-Dwass test). The surface temperature did not significantly differ between graft and control sites. These findings suggest that skin graft vascularization started by POD6 and stabilized by POD11. Because TcPO2 increases after POD4, skin grafts should remain undisturbed until at least POD11.

HIGH WATTAGE VAPING SHIFTS URINE METABOLOME TOWARD A HEALTHIER PROFILE: A RANDOMIZED CROSSOVER STUDY

Abstract Objective: We previously demonstrated in young and healthy occasional tobacco smokers that acute exposure to high wattage vaping with and without nicotine decreases transiently transcutaneous oxygen tension and arterial oxyen tension. Propylene glycol and glycerol are e-cigarette constituents that facilitate liquid vaporization and nicotine transport. As these small hydrophilic molecules have a short serum/urine half-live, we hypothesized that short-term cessation of vaping in regular users would change urine metabolic signatures. Design and method: Thirty regular e-cigarette users were enrolled in this randomized, investigator-blinded, three-period crossover-study. The periods consisted of nicotine-vaping (nicotine-session), nicotine-free vaping (nicotine-free-session), and complete cessation of vaping (stop-session), all maintained for five days before the session began. Multiparametric metabolomic analyses on urine and serum were used to verify subjects’ protocol compliance. Metabolomic analysis was performed on urine samples by proton nuclear magnetic resonance. Results: Partial least squares discriminant analysis (PLS-DA) performed on baseline serum metabolome did not allow to split up any of the three experimental session. PLS-DA performed on baseline urine metabolome allowed to split up the nicotine and the stop sessions (Figure 1.C), the nicotine-free and the stop-sessions (Figure 1.D) but not the nicotine from the nicotine-free session (Figure 1.B) as well as all three sessions (Figure 1.A). Heatmap outlines the main metabolites with variables of importance values &gt; 1 of both session as well as those identified by the PLS-DA. Baseline urine propylene glycol was lower in the stop-session compared to the nicotine-and nicotine-free sessions (all-p &lt; 0.0001). Baseline urine 3-hydroxyisovalerate and urine-pyruvate were higher in the nicotine-session vs. the nicotine-free and the stop-sessions (all-p &lt; 0.05). Compared to the stop-session, baseline urine trimethylamine-oxide and hippurate were lower in the nicotine-session (all-p &lt; 0.05). Finally, baseline N-Phenylacetyl-glycine was lower in the nicotine-session when compared to the stop-session (p &lt; 0.05). Conclusions: In conclusion, our study reveals that short-term e-cigarette cessation in regular users modified the urine metabolomic signature in a way signature in a way that suggests several modulations in hypoxia related pathways. This will need further researches focusing on cellular and molecular alterations (i.e., hypoxia-inducible Factors-1, nuclear factor-kappa B), in cell and animal models.

Efficiency of mesenchymal stromal cells (MSCs) in the treatment of patients with critical limb-threatening ischemia

Relevance. The relevance of the study is determined by the fact that hopes are placed in the cell therapy for patients with critical limb-threatening (CLI) ischemia as a method of the restoration of blood circulation in the affected limb in patients who cannot undergo surgical or endovascular intervention. Aim. To evaluate the efficiency of allogeneic MSCs for the treatment of critical lower limb ischemia (randomized placebo-controlled study).Materials and methods. The study included 34 patients with critical lower limb ischemia (grade 4 according to Pokrovsky). There were 18 patients in the MSC group, and 16 patients in the placebo group). The groups were comparable concerning age, disease duration, and comorbidities. Allogeneic MSCs (phenotype CD73+, CD90+, CD105+, CD45–, CD34–, CD14–) were injected into the posterior calf muscles. Clinical outcome, ankle pressure, transcutaneous oxygen tension (tcpO2), and pain-free walking distance (PFWD) were evaluated. The patients were followed-up for 12–36 months. According to the clinical outcome in each group, the patients were divided into subgroups with «effect (+)» or «effect (–)». In 2 patients, there was an «uncertain clinical outcome». When analyzing the results, these patients were assigned to one or another subgroup.Results. In the MSC and placebo groups, the clinical outcome assessed as «effect (+)» or «effect (–)» did not differ (OR 1.5; 95 % CI 0.34–6.7). With different variants of group formation and with the assignment of patients with an «uncertain clinical outcome» to a one or another subgroup, the final results neither differed. According to instrumental research methods (PFWD, tcpO2, ankle pressure, angiography), there were no differences in the MSC and placebo groups. Conclusion. With different variants of analysis and group formation, no convincing evidence that allogeneic MSCs can be effective for the treatment of critical lower limb ischemia have been obtained.

Transcutaneous oxygen tension and ankle brachial pressure index as predictors of outcome in diabetic foot

Transcutaneous oxygen tension and ankle brachial pressure index as predictors of outcome in diabetic foot

Diabetic foot: diabetic ulcer care

Background. Diabetic foot syndrome (DFS) is the presence of an infection and/or ulcer defect of the foot associated with neuropathy and circulatory disorders of the lower extremities of varying severity. Insensitivity of the foot, its deformation and constant load lead to the formation of necrosis under hyperkeratosis with the potential infectious process development.&#x0D; Objective. To describe the features of the course and treatment of DFS.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. Classification of diabetic ulcers is carried out according to the PEDIS system, where P means perfusion, E – extent, D – depth, I – infection, S – sensation. To assess the circulatory status of the lower extremities, the ankle-brachial index (ABI) and transcutaneous oxygen tension are determined. Critical ischemia is determined by the following criteria: tibial systolic blood pressure &lt;50 mm Hg, big toe blood pressure &lt;30 mm Hg, or transcutaneous oxygen tension &lt;30 mm Hg, or ABI &lt;0.5. DFS treatment involves unloading the foot with the help of special shoes or orthoses, ultrasonic or vacuum cavitation of wounds, surgery, antibiotic therapy. If necessary, anti-pseudomonad antibiotics should be used (ceftazidime, cefoperazone, cefepime, imipenem, meropenem, ciprofloxacin, amikacin). 95 % of the microorganisms present in the world are able to coexist in the form of biofilms – communities of microorganisms in a matrix of polymers (mucopolysaccharides), which are released by the same bacteria. Taking this into account, one should choose antibiotics that can penetrate biofilms. Diabetic ulcers should be covered with dressings such as Hydroclean plus, which contain an antiseptic that protects the wound from secondary infection, prevents excessive evaporation of moisture and has an atraumatic contact layer that prevents traumatization of the young granulation tissue. This dressing continuously releases Ringer’s solution into the wound and absorbs the wound exudate, creating a continuous washing effect. Lacerta (“Yuria-Pharm”) can be used to stimulate the regeneration of long-term defects of connective tissues. Lacerta activates the migration and proliferation of fibroblasts, accelerates their metabolic activity, and enhances angiogenesis. Other methods of accelerating of the wound healing include the use of cryopreserved amniotic membranes and the injection of stem cells.&#x0D; Conclusions. 1. DFS is the presence of an infection and/or ulcerative defect of the foot associated with neuropathy and circulatory disorders of the lower extremities. 2. Classification of diabetic ulcers is carried out according to the PEDIS system. 3. Treatment of DFS involves unloading the foot with special shoes or orthoses, ultrasonic or vacuum cavitation of wounds, antibiotic therapy, surgery. 4. It is advisable to cover diabetic ulcers with hydrogel bandages. 5. Lacerta can be used to stimulate the regeneration of persistent skin defects.

Photo-Optical Transcutaneous Oxygen Tension Measurement Is of Added Value to Predict Diabetic Foot Ulcer Healing: An Observational Study.

Currently, transcutaneous oxygen tension measurement (TCpO2) is the most favorable non-invasive test for diabetic foot ulcer (DFU) healing prognosis. Photo-optical TCpO2 is novel, less time-consuming and more practical in use compared to regular electro-chemical TCpO2. We prospectively investigated the clinical value of photo-optical TCpO2 to predict DFU healing. Patients with suspected DFU undergoing conservative treatment underwent an ankle pressure, toe-pressure and photo-optical TCpO2 test. The primary endpoint was DFU wound healing at 12 months. Based on their clinical outcome, patients were divided into a DFU healing and DFU non-healing group. Healing was defined as fully healed ulcers and non-healing as ulcers that deteriorated under conservative treatment or that required surgical amputation. Differences between groups were analyzed and an optimal TCpO2 cut-off value was determined. In total, 103 patients were included, of which 68 patients (66%) were classified as DFU healing. The remaining 35 patients (34%) had deteriorated ulcers, of which 29 (83%) eventually required surgical amputation. An optimal TCpO2 cut-off value of 43 mmHg provided a sensitivity, specificity and odds ratio of 0.78, 0.56 and 4.4, respectively. Photo-optical TCpO2 is an adequate alternative tool to validate the vascular status of the lower extremity indicating healing prognosis in patients with DFU. Therefore, we recommend that photo-optical TCpO2 can be safely coapplied in clinical practice to assist in DFU treatment strategy.

Evaluating the effects of sedentary behaviour on plantar skin health in people with diabetes

BackgroundDiabetes-Related Foot Ulcers (DRFUs) are a common and devastating consequence of Diabetes Mellitus and are associated with high morbidity, mortality, social and economic costs. Whilst peak plantar pressures during gait are implicated cited as a major contributory factor, DRFU occurrence has also been associated with increased periods of sedentary behaviour. The present study was designed aimed to assess the effects of sitting postures on plantar tissue health. MethodsAfter a period of acclimatisation, transcutaneous oxygen tensions (TCPO2) and inflammatory cytokines (IL-1α and IL-1RA) were measured at the dorsal and plantar aspects of the forefoot before, during and after a 20-min period of seated-weight-bearing in participants with diabetes (n = 11) and no diabetes (n = 10). Corresponding interface pressures at the plantar site were also measured. ResultsDuring weight-bearing, participants with diabetes showed increases in tissue ischaemia which were linearly correlated proportional to plantar pressures (Pearson's r = 0.81; p < 0.05). Within the healthy group, no such correlation was evident (p > 0.05). There were also significant increases in post seated weight-bearing values for ratio for IL-1α and IL-1RA, normalised to total protein, post seated weight-bearing in participants with diabetes compared to healthy controls. ConclusionThis study shows that prolonged sitting may be detrimental to plantar skin health. It highlights the need to further examine the effects of prolonged sitting in individuals, who may have a reduced tolerance to loading in the plantar skin and soft tissues.

Determination of transcutaneous oxygen tension for evaluating the degree of ischemia in patients with diabetic foot syndrome

One of the main syndromes that poses a direct threat to the patient's ability to work and life is diabetic foot syndrome (DFS). It is known that DFS is caused by a complex of disorders of the anatomical and functional state of the foot due to neuro-ischemic changes caused by prolonged hyperglycemia. The aim of styding was to investigate the value of transcutaneous oxygen tension during the performance of revascularization and rehabilitation interventions in patients with DFS. We studied 114 patients with purulent-necrotic forms of DFS with moderate and severe diabetes, who were determined by the value of transcutaneous oxygen tension during hospital treatment.Therefore, determination of transcutaneous oxygen tension is the most informative way to assess the degree of ischemia before and after revascularization operations. When the value of TcpO2 at the foot ≤25 mmHg we recommend performing the first stage of revascularization intervention. At TcPO2 values &gt;25 mmHg, revascularization was recommended for post-primary remediation of purulent-necrotic lesions and to accelerate healing in patients with large foot tissue defects after surgery for purulent-necrotic complications of DFS. When restoring the value of the transcutaneous voltage above25 mmHg it can be performed remediation interventions at almost any distal level. At values of 10-25 mmHg – it should be done more proximal level (where the determined transcutaneous value of TcpO2 is about 15-25 mmHg) of the demarcation line necrosis, as the risk of reamputation is higher than 75 %. At values of ≤10 mmHg, we recommend performing high amputations.

Involvement of microcirculation in critical ischemia: how to identify it?

Critical limb ischemia represents the most severe pattern of peripheral arterial disease (PAD) associated with the high risk of major amputation, cardiovascular events and death. The diagnosis and management of critical limb ischemia (CLI) is often challenging. Systolic ankle and toe pressure measurements are considered to be the basic techniques for the identification of PAD. However, they provide rough insight into the dependent local tissue perfusion. Furthermore, those techniques do not enable investigation of microcirculation which has crucial role in the pathogenesis of CLI. Some patients with mild deterioration of macrocirculation develop CLI if microcirculation is affected. Investigation of perfusion on macro- and local microcirculatory level enables more effective treatment: revascularization of the angiosome-related artery. The technologies capable of assessing limb tissue oxygenation or perfusion on microcirculatory level enable direct assessment of distant tissue oxygenation. Transcutaneous oxygen tension (TcPO2) measurement which was introduced in clinical practice represents one of the objective criteria for the diagnosis of CLI. Main weakness of this technique as well as laser Doppler flow measurement is low penetrance from the skin surface. Measurement of tissue blood flow on microcirculatory level can be performed with indocyanine green fluorescent imaging (ICG), contrast-enhanced magnetic resonance and vital microscopy. ICG is promising method which provides excellent informative image of tissue perfusion. However, it offers little quantitative information. Investigation of microcirculation in patients with CLI is of outmost importance because it enables insight in local tissue perfusion and oxygenation, which represents the basis of identification of most ischemic regions and provide more successful angiosome related revascularization of an affected artery.

Determinants of Bone Material Strength and Cortical Porosity in Patients with Type 2 Diabetes Mellitus.

Reduced bone material strength index (BMSi) and increased cortical porosity (CtPo) have emerged as potentially contributing to fracture risk in type 2 diabetes mellitus (T2DM) patients. To determine whether BMSi or CtPo are related to other diabetic complications. Cross-sectional observational study. Subjects recruited from a random sample of southeast Minnesota residents. A total of 171 T2DM patients (mean age, 68.8 years) and 108 age-matched nondiabetic controls (mean age, 67.3 years). Bone material strength index was measured using microindentation, skin advanced glycation end-products (AGEs) measured using autofluorescence, high-resolution peripheral quantitative computed tomography at the distal radius and tibia, assessment of diabetic microvascular complications including urine microalbuminuria, retinopathy, neuropathy, and vascular disease (ankle brachial index and transcutaneous oxygen tension [TcPO2]). All analyses were adjusted for age, sex, and body mass index. Skin AGEs were negatively correlated with the BMSi in both T2DM (r = -0.30, P < 0.001) and control (r = -0.23, P = 0.020) subjects. In relating diabetic complications to CtPo, we found that T2DM patients with clinically significant peripheral vascular disease (TcPO2 ≤ 40 mm Hg) had higher (+21.0%, P = 0.031) CtPo at the distal tibia as compared to controls; in these subjects, CtPo was negatively correlated with TcPO2 at both the distal tibia (r = -0.39, P = 0.041) and radius (r = -0.41, P = 0.029). Our findings demonstrate that bone material properties are related to AGE accumulation regardless of diabetes status, while CtPo in T2DM patients is linked to TcPO2, a measure of microvascular blood flow.

The Effects of Physical Training and Flunarizine on Walking Capacity in Intermittent Claudication

The clinical significance of drugs improving red cell deformability is not confirmed. We established the effect of physical training alone and combined with flunarizine on intermittent claudication. Twelve patients aged 48-73 years were included in the study. Pain-free walking distance on treadmill, ankle/arm pressure ratio and transcutaneous oxygen tension were measured. Walking distance increased significantly (p less than 0.05) by 130% from 75 m to 173 m during the first year when the patients were on programmed physical training. Ankle/arm pressure ratio also increased significantly (p less than 0.05) from 0.46 to 0.55 during this period. The increase in walking distance ceased when the programmed physical training was discontinued for 6 months. During the following double-blind, cross-over medication period the patients were given flunarizine 5 mg b.i.d. and placebos in randomized order for 3 months each. They also continued the same programmed physical training as during the first year. Walking distance increased, albeit not significantly, with time to 392 m after the second medication period. There was no difference, however, between flunarizine and placebo. Ankle/arm pressure ratio was of the same magnitude as at the beginning of the trial. Oxygen tension measurements did not give consistent results. We conclude that programmed physical training increased walking distance as a function of time. Flunarizine had no effect on the performance of patients with intermittent claudication.

SUN-381 Cortical Porosity Is Associated with Peripheral Small Vessel Disease in Adult Patients with Type 2 Diabetes

Patients with Type 2 Diabetes (T2D) are at higher fracture risk despite having relatively normal or even increased BMD by DXA. Increased cortical porosity has emerged as a potential factor contributing to fragility fractures in T2D. However, there is conflicting evidence whether T2D patients have increased cortical porosity. We hypothesized that microvascular complications have an important role in cortical porosity. Thus, we performed high-resolution peripheral quantitative computed tomography imaging at the distal radius and tibia to evaluate bone microarchitecture in men with T2DM age ≥ 50 yrs or postmenopausal women with T2DM and nondiabetic controls. Comprehensive diabetic complications were assessed in all patients including urine microalbuminuria, retinopathy, neuropathy (touch, temperature, and vibration sensation), ankle brachial index (ABI) and transcutaneous oxygen tension (TcPO2). Percent differences between groups were obtained from linear regression models adjusting for age, BMI, and sex. Relationships between variables were assessed using adjusted Spearman correlations. A total of 164 T2D patients (mean age 68.9 ±7.8 yrs.; 56.7% men; HbA1C=7.7 ±0.9%; mean diabetes duration 15.2 yrs.) and 107 nondiabetic controls (mean age 67.3±8.8 yrs.; 42.1% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was a trend for increased cortical porosity at the distal tibia in the T2D group (+12.2%; p=0.063) compared with nondiabetic controls. Of note, TcPO2 was negatively correlated with cortical porosity at the distal radius (r= -0.17; p= 0.039) and distal tibia (r= -0.15; p= 0.073). In particular, the Low TcPO2 (≤40 mmHg) group (n=29) had greater cortical porosity at the distal tibia (+19.6 %; p=0.037) compared with the High TcPO2 (>40 mmHg) group (n=133). In addition, the low TcPO2 group had a significant increase in cortical porosity in the distal tibia (+24.8% p=0.020) compared with nondiabetic controls. In conclusion, this is the first evidence in humans indicating that TcPO2, a measure of microvascular blood flow, is linked to cortical porosity in the distal radius and tibia in T2D patients. Our findings may explain the conflicting findings regarding cortical porosity in T2D because only T2D patients with impaired microvascular blood flow have increased cortical porosity. Collectively, our data indicate that cortical porosity is a microvascular complication of longstanding T2D.

Comparative results of isolated profundoplasty and distal bypass surgery in patients with diabetes mellitus and trophic ulcers

Aim. To compare the results of lower limb revascularization in patients with diffuse lesions of lower limb arteries who underwent femoral-distal bypass surgery and isolated reconstruction of the deep femoral artery (DFA) in the immediate postoperative period.Materials and methods. The study included 86 patients with diffuse arterial lesions of lower extremities, 52 (60.4%) men and 34 (39.6%) women with the average age of 67.3 ± 16.8 years. All patients had diffuse lesions of the arteries below the Poupart’s ligament; the condition of the lower leg arteries was 5–8.5 points on the Rutherford scale. Trophic ulcers were present in all cases. Group 1 included 48 patients who underwent reconstruction of lower leg arteries. Group 2 included 38 patients whose surgical intervention was limited to endarterectomy from the common femoral and deep femoral arteries.Results. In the early postoperative period, 1 (2.1%) patient (from group 1) died from developed myocardial infarction. The patient underwent a femoral-popliteal-tibial bypass surgery with a composite Y-shaped graft. In group 2, no fatal complications were observed. After the operation, all patients demonstrated an increase in the linear blood flow velocity in the arteries of the foot and the transcutaneous oxygen tension (TOT). The TOT level 14 days after surgery comprised 44.1 mm Hg and 39.9 mm Hg (p&gt; 0.05) in groups 1 and 2, respectively.Conclusions. In 86.8% of patients, isolated profundoplasty followed by vasotropic therapy allows the target values of TOT to be obtained, which is necessary for successful healing of lower limb trophic ulcers.

Pilot study of the safety and efficacy of angiogenic therapy in diabetic foot syndrome

BACKGROUND: The syndrome of diabetic foot remains the main cause of non-traumatic amputation of the lower extremity in the world. Even with the provision of comprehensive medical care in the conditions of a specialized center, 10-15% of patients do not succeed in healing the ulcerative defect due to the ischemic component.&#x0D; AIMS: The objective of this study is evaluation of safety and efficacy of pl-VEGF165 transfer in patients with neuroischemic type of diabetic foot syndrome.&#x0D; METHODS: The pilot study included 35 diabetic patients with neuroischemic foot ulcers (Wagner stage 1-2) who were not candidates for revascularization procedures (NCT02538705). The patients were closely monitored after repeated pl-VEGF165 intramuscular gene transfer (2,4 mg) at 1, 3, and 6 months after treatment. The primary efficacy endpoint was the surface area of the ulcers (sq.cm), the secondary endpoints were transcutaneous oxygen tension (Tcp02), ankle-brachial index (ABI), neuropathy disability score (NDS), neuropathy symptoms score (NSS), and Michigan neuropathy screening instrument (MNSI). Adverse events were monitored throughout the study.&#x0D; RESULTS: The use of pl-VEGF165 as part of complex treatment allowed to achieve wound healing in 65,7% of patients with chronic ulcerative defects, the safety of the target limb was 84%. Carrying out therapeutic angiogenesis as a part of the combined therapy ensured a reduction in the average area of the resistant to treatment defects from 3.6 [1.0; 7.05] cm2 to 0.0 [0.0;2.0] cm2 (p=0,001), which correlated with an increase in the TcPo2 index by 15% from 35 [29.5; 40.5] to 40.5 [36.0; 46.5] mm Hg (p= p=0,005) and in the ABI by 16% from 0.96 [0.82;1.08] to 1.11 [0.85; 1.24] (p=0,062). The decrease in the signs of diabetic neuropathy was determined - the scores of NSS scales and VAT decreased from 6,5 [5.75; 8.0) to 6.0 [5.25; 7.0] (p=0,004) and from 9.0 [8.0; 13.5] to 8.0 [7.0; 12.7] (p=0,001), respectively. No adverse effects associated with the use of pl-VEGF165 were recorded.&#x0D; CONCLUSIONS: Thus, preliminary results of the pilot study show that the use of pl-VEGF165 gene transfer in combination therapy allows for complete healing of neuroischemic diabetic foot ulcers in the majority of patients.

Establishing a measurement array to assess tissue tolerance during loading representative of prosthetic use

BackgroundIn the early stages of rehabilitation after primary amputation, residual limb soft tissues have not been mechanically conditioned to support load and are vulnerable to damage from prosthetic use. There is limited quantitative knowledge of skin and soft tissue response to prosthetic loading. MethodsAn in-vivo protocol was developed to establish suitable measures to assess tissue tolerance during loading representative of early prosthesis use. Ten participants without amputation one participant with trans-tibial amputation were recruited, and pressure applied to their calf in increments from 20 to 60 mmHg. Measurements were recorded at relevant skin sites including interface pressures, transcutaneous oxygen (TCPO2) and carbon dioxide (TCPCO2) tensions and inflammatory biomarkers. FindingsAt the maximum cuff pressure, mean interface pressures were between 66 and 74 mmHg, associated with decreased TCPO2 values. On the release of pressure, the ischaemic response was reversed. Significant upregulation (p < 0.05) in inflammatory biomarker IL-1α and its antagonist IL-1RA were observed at all sites immediately following loading. InterpretationThe protocol was successful in applying representative prosthetic loads to lower limb tissues and monitoring the physiological response, both in terms of tissue ischemia and skin inflammation. Results indicated that the measurement approaches were sensitive to changes in interface conditions, offering a promising approach to monitor tissue status for people with amputation.

To evaluate the role of two-dimensional perfusion angiography as a predictor in wound healing outcomes in patients of critical limb ischemia

Aim: The study was aimed to evaluate the role of two-dimensional (2D) perfusion angiography (PA) as a predictor in wound healing outcomes in patients of critical limb ischemia. Subject and Methods: It was a pilot study conducted over a period of 16 months after taking informed consent and institutional ethical clearance. The study included 40 patients of which 8 were lost to follow-up, hence the prospective data of 32 patients was collected and analyzed. Patients were subjected to endovascular intervention and 2D perfusion software was applied to the digital subtraction angiography images and its parameters were assessed. Transcutaneous oxygen tension (TcPO2) was measured pre- and postintervention and patients were closely followed up for the time taken for wound healing. Results: The median age was 62 years ranging from 30 to 85 years. Most common comorbidity was diabetes (21/32 patients). The mean Ankle–Brachial Index in the study was 0.55 and mean TcPO2 at admission was 26.5 mm of Hg. Most common involved angiosome was percutaneous transluminal angioplasty angiosome. Fifteen patients underwent direct, 9 indirect, and remaining 8 patients underwent revascularization in both territories. The mean percent improvement in TcPO2 was higher in indirect when compared to direct revascularization but it was not statistically significant. The time taken in wound healing was significantly higher in diabetics when compared to nondiabetics with P = 0.03. Most reliable parameter in 2D PA was area under the curve (AUC) which correlated with increase in volume of tissue perfusion. Patients with >100% improvement in AUC showed significantly better wound healing rates when compared to patients with <100% improvement (P = 0.04). Conclusion: This proved 2D PA as a reliable method for immediate assessment of improvement in microcirculation and as a predictor for wound healing. It can also be used as a real-time tool in optimizing the need and determining the end point for revascularization.

Phenomenon of unstable tcpO2 level in transcutaneous oximetry in patients with diabetes mellitus

The back of the foot is a standard region for measuring transcutaneous oxygen tension (tcpO2) with a reliably determined threshold of ischaemia, but such measurement reflects blood supply of only a portion of angiosomes of the foot. Determining the reference values of tcpO2 in other regions of the lower extremity is of current importance. However, measuring the tcpO2 level on the plantar surface and in some other regions not uncommonly reveal a phenomenon of its steady decrease instead of formation of a plateau. The purpose of the present study was to analyse the frequency of the phenomenon of a steady decrease in ptcO2 level while performing transcutaneous oximetry in various zones of the lower extremity. We retrospectively analysed the results of a total of 160 measurements of tcpO2 in 35 patients with diabetes mellitus. The patients' mean age amounted to 68 (47-87) years, with the duration of diabetes mellitus averaging 14 (1-24) years. The male-to-female ratio was 60:40. Seventy-seven percent of patients had foot ulcers/wounds, 34% of patients had a history of previously endured revascularization. The examination was carried out in the dorsal, plantar, medial plantar regions of the foot, on the medial surface of the crus and in the subclavian region, using the TCM 400 monitoring device (Radiometer, Denmark). The measurements were performed by an experienced operator in strict accordance with the manufacturer's recommendations. We evaluated the average value of tcpO2 between the 15th and 19th minutes of measurement and the peculiarities of the tpcO2 curve (plateau/increase/decrease of the value) within this time interval. The mean tcpO2 value in the medial plantar region was significantly higher than that on the back of the foot: 34 (3-70) versus 22 (1-59) mm Hg, p=0.003. A portion of measurements demonstrated a steady decrease in the tpcO2 during the measurement up to the 40th minute. Complying with the stable plateau phase criteria we had developed were 92% of measurements in the subclavian region, 100% - in the middle third of the crus, 76% - on the back of the foot, 77% - in the medial plantar region and 43% - on the plantar surface of the foot. CONCLUSIONS: 1) the revealed phenomenon of a steady decrease of tcpO2 in some patients needs to be taken into consideration in clinical practice and deserves further study; 2) the nature of this phenomenon is unclear, with a possible effect of skin creams on the results of the measurements; 3) it is advisable to include into the functions of the devices for transcutaneous oximetry an algorithm for confirmation of the true phase of the plateau and calculation of the mean tcpO2 value for a chosen period; 4) despite the need for measurement of tcpO2 in the 'alternative zones' it is necessary to thoroughly study the reliability of the data in these zones and to determine the normal values of the parameter separately for each of them.

One-year Results of pCMV-VEGF165 Gene Transfer in Patients with Critical Lower Limb Ischemia Due to Peripheral Atherosclerosis and Diabetes Mellitus

Introduction - atherosclerotic peripheral arterial disease is common in patients with diabetes mellitus (DM) and leads to a significant increase in amputation rates. Induction of angiogenesis may be a promising technique in improving limb salvage rates and quality of life in patients with critical limb ischemia (CLI) and DM. Methods - The study was divided into experimental and clinical parts. Experiment was performed using a model of surgical skin wound in Wistar rats with alloxan-induced DM. Experimental animals were treated with 60mcg (N=8) or 200mcg (N=8) of pCMV-VEGF165. Animals in control group were treated with water for injections. At 10 days the animals were withdrawn from the experiment with following morphological and immunohistochemical assessment of the wound and surrounding soft tissues. Clinical study included 140 patients with CLI and DM. Patients were divided into 4 groups: group I – arterial revascularization and conservative therapy (N=45), group II –conservative treatment (N=40), group III – arterial revascularization, conservative therapy, and pCMV-VEGF165 gene transfer (N=30), group IV – conservative treatment and pCMV-VEGF165 gene transfer (N=25). Limb salvage rates, lethal outcomes, degree of ischemia, pain-free walking distance, ankle-brachial index (ABI), transcutaneous oxygen tension (tcp02), blood velocities, and neurological symptom score (NSS) were assessed within 1 year after treatment. Results - experimental part: epithelization and granulation rates were higher in diabetic animals treated with pCMV-VEGF165 (p=0.038). Histological and immunohistochemical studies have revealed a better multi-caliber vessel growth in rats which received gene therapy. Clinical part: after one year amputation rates and lethal outcomes were lower in patients in group III (16.7% of amputations as compared to group I, p=0.041; 13.3% of lethal outcomes). When assessing the results of treatment among the patients who received conservative treatment, amputation rates and lethal outcomes were lower in subjects treated by gene transfer (36% of amputations, p = 0.0496; 16% of lethal outcomes). Postprocedural patency rates at 6 months were comparable between the patients in groups I and III (66.7% and 70%, respectively), while the number of amputations was significantly lower in subjects treated by pCMV-VEGF165 gene transfer (33.3% and 86.7% of amputations in groups III and I, respectively, p=0.013). When comparing the difference in pain-free walking distance, better results were obtained in patients in group IV as compared to group II (p=0.032). When comparing the perfusion parameters and neurological score between the patients in groups II and IV, ABI was not affected by gene therapy, while the subjects in group IV had improved tcpO2 values, blood velocity, and NSS score (p=0.028, p=0.047, p=0.044, respectively). Conclusion - 1. pCMV-VEF165 gene transfer leads to improved wound healing rates and increased vascularization of granulation tissue in diabetic experimental animals (p=0.038). 2. Gene therapy improves perfusion and increases limb salvage rates in diabetic patients with CLI when used in combination with arterial revascularization or conservative therapy within 1 year after treatment.

Relationship of transcutaneous oxygen tension with age and skin elasticity in Korean women.

Oxygen has several positive effects on the skin, including improving collagen synthesis and accelerating wound healing. However, only a few studies have investigated the relationship between skin oxygenation and skin aging parameters. Therefore, this study aimed to assess the correlation between skin oxygenation and skin aging parameters-elasticity, hydration, sebum, color (lightness, redness), and blood perfusion-in Korean women. We evaluated the transcutaneous partial pressure of oxygen, also known as transcutaneous oxygen tension (TcPO2 ), and skin aging parameters, including elasticity, hydration, sebum, color (lightness or redness), and blood perfusion, in the cheek of 34 healthy women (aged 20-69years) and assessed the correlation between TcPO2 and other skin aging parameters using IBM SPSS Statistics 25 software (SPSS Inc). Facial TcPO2 was negatively correlated with age (P<.05). There were positive correlations between facial TcPO2 and elasticity parameters (P<.01). We noted no correlation between facial TcPO2 and skin lightness; however, skin lightness tended to slightly improve with increasing TcPO2 . Skin aging parameters, including hydration, sebum, skin redness, and blood perfusion, showed no correlations with TcPO2 . In Korean women, facial TcPO2 tends to decrease with increasing age and is positively correlated with gross, net, and biological skin elasticity. Therefore, this study demonstrated that oxygen tension of facial skin can be a major causative factor of skin aging.