Search Results (32)

Background and Objectives: This study investigated the frequency and clinical significance of subclinical but substantial peripheral arterial disease (PAD), identified using PAD evaluation, including pulse volume recording/ankle–brachial index (PVR/ABI), transcutaneous oxygen pressure (TcpO2), and skin perfusion pressure (SPP) tests in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 54 patients with PAD evaluation results at or after AAV diagnosis. PVR/ABI and/or TcpO2 and/or SPP were performed on the same day. Abnormal PVR/ABI, TcpO2, and SPP were defined as PVR/ABI < 0.97, TcpO2 < 40 mmHg, and SPP < 50 mmHg, respectively. Poor outcomes included all-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accidents, and acute coronary syndrome after PAD evaluation. Results: The median age of the 54 patients was 67 years, and 48.1% were male. In total, 3 of 54 patients (5.6%), 6 of 16 (37.5%), and 6 of 23 (26.1%) had abnormal PVR/ABI, TcpO2, and SPP, respectively. The concordance rate between abnormal PVR/ABI and abnormal TcpO2 or SPP was very low. Among the 54 patients, 5 (9.3%) died, and 2 (3.7%) progressed to ESKD. Abnormal SPP was significantly associated with cutaneous and renal manifestations at the time of PAD evaluation and had the potential to predict progression to ESKD during follow-up in patients with AAV. Conclusions: This study is the first to reveal the clinical usefulness of PAD evaluation: abnormal SPP may have the potential to identify subclinical but substantial PAD and can predict simultaneous kidney involvement as well as future progression to ESKD in patients with AAV. Full article

Pressure injuries (PIs) are typically characterized by lesions of the dermis and subcutaneous tissue; they result from a downward force exerted on the area between a bony prominence and an external surface. Transcutaneous oxygen pressure (TcPO2) measurements are a standardized method for measuring tissue oxygen pressure. Standardized TcPO2 measurement data are lacking in regions susceptible to pressure injury. It is unclear whether the absence of data can be attributed to the unreliability and variability of the measurements obtained. This study aimed to assess the reliability and repeatability of TcPO2 measurements conducted using a fluorescence-sensitive photo-optical sensor at three sites on the foot where PIs can occur but for which no data are available. Thirty volunteers participated in this study. TcPO2 was measured in two sessions, one week apart, at the lateral of the fifth metatarsal head, the styloid process, and the lateral malleolus of both feet. TcPO2 (mmHg) exhibited moderate reliability for the left fifth metatarsal and right fifth metatarsal styloid process (ICC: 0.575 and 0.624, respectively). The right fifth metatarsal and the right and left lateral malleoli demonstrated good and excellent reliability of the styloid process of the left fifth metatarsal, with ICC values of 0.810, 0.816, 0.763, and 0.900, respectively. The implementation of a fluorescence-sensitive photo-optical sensor for the measurement of TcPO2 in the designated regions yielded reliable and reproducible measurements. Full article

Background/Objectives: Intermittent pneumatic impulse compression (IIC) is a well-established drainage treatment that reduces edema and enhances arterial blood flow. While widely utilized in various medical fields, its efficacy in dermatology, particularly for stasis dermatitis, remains underexplored. This study evaluates the effectiveness of IIC in inpatients with bilateral stasis dermatitis by comparing standard therapy alone versus standard therapy with additional IIC on one leg over five days. Methods: Seventeen patients from the Dermatology Department at University Hospital Duesseldorf were enrolled. Both legs received standard therapy, while one randomized leg received additional IIC for four hours daily. Measurements, including transcutaneous oxygen pressure (tcpO₂), leg circumference, and pain sensation, were taken at baseline, the first day post-IIC, and after five days. Statistical analysis included paired t-tests, with significance set at p < 0.05. Results: The IIC-treated legs exhibited significant improvements in tissue oxygen saturation (MD = 19.87 mmHg, SD = 27.82, p = 0.012) and reduced ankle circumference (MD = −2.125 cm, SD = 1.593, p < 0.0001). No significant changes were observed in tcpO₂ or circumference in the non-IIC-treated legs. Other leg circumference measurements (calf, above the knee) did not demonstrate significant improvements in either group. Pain levels remained stable under IIC therapy. Conclusions: This proof-of-concept study provides evidence supporting IIC as a beneficial adjunct therapy for stasis dermatitis, demonstrating significant edema reduction and enhanced oxygenation. Further investigations are warranted to confirm these findings and expand clinical applicability. Full article

Background/Objectives: Due to poor perfusion, diabetic foot ulcers (DFUs) create hypoxic environments, and their chronicity represents a negative factor in wound healing. Transcutaneous oxygen pressure (TcPO₂) is a non-invasive method that provides information on oxygen supply to microvascular circulation, useful for determining the severity and progression of peripheral arterial disease (PAD) as well as potentially predicting DFU healing. However, the current literature does not provide strong support for the use of TcPO₂ as an independent predictive tool. Methods: This protocol aims to systematically review the available evidence according to PRISMA (2020) guidelines, registered with the International Prospective Register of Systematic Reviews (registration number: CRD42024505907). The following databases will be used: Cochrane Library, EMBASE, Ovid Medline, PubMed, and Web of Science. Additionally, a manual search will be conducted through the references of the included articles. Results: The systematic review will summarize the current evidence on the prognostic value of TcPO₂ in DFU healing, identifying gaps in knowledge and potential areas for future research. Conclusions: The findings of this study may clarify the prognostic value of TcPO₂ in DFU healing, which could ultimately facilitate clinical management, decision-making, patient care, and potentially reduce treatment costs. Full article

Background: Patients with no-option chronic limb-threatening ischemia (NoCLTI), lacking suitable distal arteries for conventional revascularization, face major limb amputation. The 1-year mortality rate after major amputation is 48.3%, increasing to 70.9% in 3 years. Open deep venous arterialization (DVA) offers a promising alternative for limb salvage, achievable through open, endovascular, or hybrid approaches. We aim to provide a comprehensive, step-by-step guide to performing open DVA in NoCLTI patients, addressing preoperative and postoperative considerations as well as the technical details of the procedure. Methods: Patient selection for open DVA focuses on individuals with NoCLTI at high risk for amputation. Preoperative assessments include evaluating risk factors, determining limb threat severity using the Wound, Ischemia, and foot Infection (WIfI) score, and mapping anatomical patterns via the Global Limb Anatomic Staging System (GLASS). The procedure involves identifying the target artery using Doppler ultrasound, performing microdissection to expose the artery and vein, ligating proximal vein branches, and creating a side-to-side anastomosis. Venous valves are disrupted with a valvulotome to allow antegrade flow. A proximal bypass graft may be applied if necessary. Results: Postoperatively, patients are monitored for 2–4 days with frequent Doppler assessments. Anticoagulation therapy begins with a heparin drip, transitioning to oral agents and/or dual antiplatelet therapy. Wound care includes deferred debridement for 2–4 weeks and may involve negative-pressure therapy. Follow-up involves weekly visits for the first month, and then at 3 months, and every 6 months thereafter, with surveillance using transcutaneous oxygen measurement, the toe–brachial index, and arterial duplex ultrasound. Conclusions: Open DVA represents a viable limb salvage option for patients with NoCLTI, potentially avoiding major amputations and improving quality of life. Success depends on careful patient selection, a meticulous surgical technique, and comprehensive postoperative care. Full article

Background and Objectives: According to the International Working Group on Diabetic Foot (IWGDF) risk classification, the estimated risk of developing a diabetic foot ulcer (DFU) is much higher in patients with a history of DFUs (Grade 3) compared to those with a peripheral neuropathy but without a history of DFUs (Grades 1 and 2). It has been suggested that microcirculation impairment is involved in DFU genesis and could be taken into account to refine the existing risk classification. The aim of this study was to evaluate microcirculation parameters in patients with diabetes according to their estimated DFU risk. Materials and Methods: A total of 172 patients with type 2 diabetes associated with a peripheral neuropathy and/or a history of DFUs were included and classified into two groups (Grade 1–2 and Grade 3) according to the IWGDF classification. All patients underwent an evaluation of peripheral neuropathy, plantar sudomotor function, and skin microcirculation parameters. These different parameters were compared between both groups. Results: There was no significant difference between the two groups in terms of age, diabetes duration, transcutaneous oxygen pressure level, skin microcirculatory reactivity, neuropathy disability score, neuropathy symptom score, or thermal sensitivity. Patients in Grade 3 were more likely to present with retinopathy (OR 3.15, 95%CI [1.53; 6.49]) and severe sudomotor dysfunction (OR 2.73 95%CI [1.29; 5.80] but less likely to have abnormal VPT (OR 0.20 95%CI [0.05; 0.80]). Conclusions: The present study found more retinopathy and a more pronounced alteration to sudomotor function in Grade 3 patients, suggesting that these parameters could be considered to better identify patients at high risk of DFUs. Full article

The results of large cardiovascular studies indicate that SGLT-2 inhibitors may increase the risk of leg amputations. This study aims to investigate whether dapagliflozin therapy affects peripheral vascular oxygenation, i.e., microcirculation in the foot, as measured by transcutaneous oxygen pressure (TcPO2) in patients with type 2 diabetes (T2DM) and peripheral arterial disease (PAD) compared to patients without PAD. The patients with PAD were randomized into two groups. In the first 35 patients with PAD, dapagliflozin was added to the therapy; in the other 26 patients with PAD, other antidiabetic drugs were added to the therapy. Dapagliflozin was added to the therapy in all patients without PAD. TcPO2 measurement, Ankle Brachial Index (ABI), anthropometric measurements, and laboratory tests were performed. After a follow-up period of 119.35 days, there was no statistically significant difference in the reduction of mean TcPO2 values between the group with T2DM with PAD treated with dapagliflozin and the group with T2DM with PAD treated with other antidiabetic drugs (3.88 mm Hg, SD = 15.13 vs. 1.48 mm Hg, SD = 11.55, p = 0.106). Patients with control TcPO2 findings suggestive of hypoxia (TcPO2 < 40 mm Hg) who were treated with dapagliflozin had a clinically significant decrease in mean TcPO2 of 10 mm Hg or more (15.8 mm Hg and 12.90 mm Hg). However, the aforementioned decrease in TcPO2 was not statistically significantly different from the decrease in TcPO2 in the group with PAD treated with other diabetic medications (p = 0.226, p = 0.094). Based on the available data, dapagliflozin appears to affect tissue oxygenation in T2DM with PAD. However, studies with a larger number of patients and a longer follow-up period are needed to determine the extent and significance of this effect. Full article

Background/Objectives: To analyze the best noninvasive tests prognosis marker in patients with diabetic foot ulcer (DFU) who underwent endovascular revascularization based on clinical outcomes, such as healing rate, time to heal, and free amputation survival after at least a six-month follow-up. Methods: A multicentric prospective observational study was performed with 28 participants with ischemic or neuroischemic DFU who came to the participant centers and underwent endovascular revascularization between January 2022 and March 2023. Toe systolic pressure (TP), ankle systolic pressure (AP), the ankle brachial pressure index (ABPI), the toe brachial pressure index (TBPI), transcutaneous pressure of oxygen (TcPO₂), and skin perfusion pressure (SPP) were evaluated using PeriFlux 6000 System, Perimed, Sweden, before (Visit 0) and four weeks after revascularization (Visit 1). The primary clinical outcome was an evaluation of the clinical evolution of noninvasive tests comparing Visit 0 and Visit 1, estimating the sensitivity for predicting wound healing of noninvasive tests at six months following initial recruitment. Results: After six months, 71.43% (n = 20) of DFU healed, four patients (14.3%) received major amputations, and one (3.5%) died. The two tests that best predicted wound healing after revascularization according to the ROC curve were TcPO₂ and TP with sensitivities of 0.89 and 0.70 for the cut-off points of 24 mmHg and 46 mmHg, respectively. Conclusions: TcPO₂ and TP were the two tests that best predicted wound healing in patients who underwent endovascular revascularization. Clinicians should consider the importance of the evaluation of microcirculation in the healing prognosis of patients with diabetic foot ulcers. Full article

Peripheral arterial disease (PAD) prevalence and diabetes mellitus (DM) prevalence are continuously increasing worldwide. The strong relationship between DM and PAD is highlighted by recent evidence. PAD diagnosis in diabetic patients is very important, particularly in patients with diabetic foot disease (DFD); however, it is often made difficult by the characteristics of such diseases. Diagnosing PAD makes it possible to identify patients at a very high cardiovascular risk who require intensive treatment in terms of risk factor modification and medical therapy. The purpose of this review is to discuss the diagnostic methods that allow for a diagnosis of PAD in diabetic patients. Non-invasive tests that address PAD diagnosis will be discussed, such as the ankle-brachial index (ABI), toe pressure (TP), and transcutaneous oxygen pressure (TcPO2). Furthermore, imaging methods, such as duplex ultrasound (DUS), computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA), are described because they allow for diagnosing the anatomical localization and severity of artery stenosis or occlusion in PAD. Non-invasive tests will also be discussed in terms of their ability to assess foot perfusion. Foot perfusion assessment is crucial in the diagnosis of critical limb ischemia (CLI), the most advanced PAD stage, particularly in DFD patients. The impacts of PAD diagnosis and CLI identification in diabetic patients are clinically relevant to prevent amputation and mortality. Full article

Background: We performed gene therapy for critical limb ischemia in thromboangiitis obliterans (TAO) by the intramuscular administration of plasmids of the vascular endothelial growth factor gene (VEGF 165) with or without bone marrow-derived stem cells. Methods: The 21 patients were randomly assigned to three groups: A—with dual therapy, cells and plasmid; B—plasmid only; and C—control group, where patients received intramuscular injections of saline. Serum VEGF levels, the ankle–brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and the rest pain measured by the visual analog scale (VAS) were determined sequentially before treatment, and then 1 and 3 months after treatment. Results: In the treatment groups, serum VEGF levels increased by 4 weeks and returned to baseline values after 3 months. ABI after 12 weeks increased by an average of 0.18 in group A, and 0.09 in group B and group C. TcPO2 increased by an average of 17.3 mmHg in group A, 14.1 mmHg in group B, and 10.7 mmHg in group C. The largest pain decrease was observed in group A and averaged 5.43 less pain intensity. Conclusions: Gene therapy using the VEGF plasmid along with or without bone marrow-derived mononuclear cells administered intramuscularly into an ischemic limb in TAO is a safe and effective therapy. Full article

Objectives: The coexistence of arterial compression with neurogenic thoracic outlet syndrome (TOS) is associated with a better post-surgical outcome. Forearm transcutaneous oxygen pressure (TcpO₂) using the minimal decrease from rest of oxygen pressure (DROPmin) can provide an objective estimation of forearm ischemia in TOS. We hypothesized that a linear relationship exists between the prevalence of symptoms (PREVs) and DROPmin during 90° abduction external rotation (AER) provocative maneuvers. Thereafter, we aimed to estimate the proportion of TOS for which arterial participation is present. Methods: Starting in 2019, we simultaneously recorded forearm TcpO₂ recordings (PF6000 Perimed^®) and the presence/absence of ipsilateral symptoms during two consecutive 30 s AER maneuvers for all patients with suspected TOS. We retrospectively analyzed the relationship between the prevalence of symptoms and DROPmin results. We estimated the number of cases where ischemia likely played a role in the symptoms, assuming that the relationship should start from zero in the absence of ischemia and increase linearly to a plateau of 100% for the most severe ischemia. Results: We obtained 2560 TcpO₂ results in 646 subjects (69% females). The correlation between PREVs and DROPmin was 0.443 (p < 0.001). From these results, we estimated the arterial participation in TOS symptoms to be 22.2% of our 1669 symptomatic upper limbs. Conclusions: TcpO₂ appears to be an interesting tool to argue for an arterial role in symptoms in TOS. Arterial participation is frequent in TOS. Whether DROPmin could predict treatment outcomes better than the sole presence of compression is an interesting direction for the future. Full article

Gender, through genetic, epigenetic and hormonal regulation, is an important modifier of the physiological mechanisms and clinical course of diseases. In diabetes mellitus, there are gender differences in incidence, prevalence, morbidity, and mortality. This disease also has an impact on the microvascular function. Therefore, this cross-sectional study was designed to investigate how gender affects the cutaneous microcirculation. We hypothesized that gender should be an important factor in the interpretation of capillaroscopy and transcutaneous oxygen saturation results. The study group consisted of 42 boys and 55 girls, uncomplicated diabetic pediatric patients. Females (F) and males (M) did not differ in terms of age, age at onset of diabetes, or diabetes duration. Furthermore, they did not differ in metabolic parameters. The comparison showed that group F had lower BP, higher pulse, and higher HR than group M. Group F had significantly lower creatinine and hemoglobin levels than group M. In children and adolescents with type 1 diabetes without complications, there was a gender difference in microcirculatory parameters. The resting transcutaneous partial pressure of oxygen was significantly higher in females than in males. However, there were no gender-related differences in basal capillaroscopic parameters or vascular reactivity during the PORH test. Our results indicate that studies investigating the structure and function of the microcirculation should consider the role of gender in addition to known cofactors such as puberty, body mass index, physical activity, and cigarette smoking. Full article

This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the function of diabetes duration. Sixty-seven patients with type 1 diabetes mellitus (T1D), aged 8 to 18 years, and twenty-eight age- and sex-matched healthy subjects were included in the analysis. Diabetic patients were divided into subgroups based on median disease duration. The subgroups differed in chronological age, lipid levels, and thyroid hormones. Capillaroscopy was performed twice: at baseline and then again after the PORH test. Transcutaneous oxygen pressure also was recorded under baseline conditions during and after the PORH test. Comparison of capillaroscopy and transcutaneous oxygen pressure parameters at rest and after the PORH showed no statistically significant difference between the subgroups. This remained true after adjusting for variables that differentiated the two subgroups. However, in the group of patients with long-standing diabetes, significant negative correlations were observed between the Coverage value after the PORH test and capillary reactivity with TcPO₂_zero (biological zero). Significant positive correlations were also found between distance after the PORH test and TcPO₂_zero. The results of our study indicate that in patients with a shorter duration of diabetes, the use of multiple tests provides a better characterization of the structure and function of microcirculation because the onset of dysfunction does not occur at the same time in all the tests. Full article

Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with ”no-option“ critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment. Methods: In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (N = 22) were considered as responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (N = 13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression, and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors, and the risk of major amputation. Results: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO₂) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI), and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP > 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (N = 22) had significantly improved TcPO₂ and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (N = 20) had significantly reduced pain scale after BMCs transplant, compared to the non-RAS-acting agents group. Similar results, reduced pain scale and improved TcPO₂, were achieved in patients treated with atorvastatin and RAS-acting agents (N = 17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. Conclusions: CRP and TcPO₂ were prognostic factors of the responders, while CRP value, ABI, and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO₂ and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responders and previous treatment before BMCs transplant with RAS-acting agents alone or with atorvastatin were significant. Full article

The measurement of partial pressures of oxygen (O₂) and carbon dioxide (CO₂) is fundamental for evaluating a patient’s conditions in clinical practice. There are many ways to retrieve O₂/CO₂ partial pressures and concentrations. Arterial blood gas (ABG) analysis is the gold standard technique for such a purpose, but it is invasive, intermittent, and potentially painful. Among all the alternative methods for gas monitoring, non-invasive transcutaneous O₂ and CO₂ monitoring has been emerging since the 1970s, being able to overcome the main drawbacks of ABG analysis. Clark and Severinghaus electrodes enabled the breakthrough for transcutaneous O₂ and CO₂ monitoring, respectively, and in the last twenty years, many innovations have been introduced as alternatives to overcome their limitations. This review reports the most recent solutions for transcutaneous O₂ and CO₂ monitoring, with a particular consideration for wearable measurement systems. Luminescence-based electronic paramagnetic resonance and photoacoustic sensors are investigated. Optical sensors appear to be the most promising, giving fast and accurate measurements without the need for frequent calibrations and being suitable for integration into wearable measurement systems. Full article