Search Results (37)

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by an impaired ventilatory response to hypercapnia and hypoxia, particularly during sleep, and frequently associated with autonomic dysfunction. It is caused by pathogenic variants in the PHOX2B gene. Although CCHS is typically diagnosed in the neonatal period, milder forms may present later in infancy or childhood, often triggered by respiratory infections. Case presentation: We report the case of 16-month-old male diagnosed with CCHS following an episode of hypoxemic–hypercapnic respiratory failure during respiratory syncytial virus (RSV) infection. His medical history included neonatal respiratory distress requiring oxygen therapy and recurrent wheezing. At 15 months, he developed acute respiratory distress with severe hypercapnia (PaCO₂ 70 mmHg), requiring admission to the Pediatric Intensive Care Unit and invasive mechanical ventilation. Persistent sleep-related hypercapnia and hypoxemia prompted evaluation for central hypoventilation, confirmed by means of transcutaneous capnography and nocturnal pulse oximetry. Genetic testing revealed a de novo nonsense mutation in exon 1 of PHOX2B (p.Tyr14Ter). Brain magnetic resonance imaging showed diffuse white matter changes suggestive of gliosis. Further investigations identified early-onset systemic hypertension, requiring antihypertensive therapy. The patient was discharged on nocturnal non-invasive ventilation and enrolled in a neurodevelopmental rehabilitation program. Conclusions: This case highlights the phenotypic variability of CCHS and the importance of considering this diagnosis in children presenting with unexplained hypercapnia and sleep-related hypoxemia. It underscores the need for comprehensive autonomic evaluation, including blood pressure monitoring. The p.Tyr14Ter variant may allow partial protein function, potentially accounting for the relatively mild phenotype. Full article

Background/Objectives: Hyperspectral imaging (HSI) facilitates noninvasive assessment of tissue perfusion in patients with peripheral arterial disease. However, available studies are either based on small cohorts and provide no comparison to standard methods or only one-time measurements. Methods: In this prospective cohort study, assessment of tissue perfusion with transcutaneous oxygen pressure (TcPO2) measurement and HSI before (1 day) and after revascularization (1–3 days) in patients with Rutherford category 3–6 was performed. The primary endpoint was change in tissue perfusion evaluated with the different methods. HSI and TcPO2 were correlated with clinical improvement after revascularization. Results: Significant improvement in the perfusion was detected by tissue oxygenation in the microcirculation (StO2; improvement +12%, mean difference 5 ± 15.9, p < 0.001) and near-infrared spectroscopy (NIR; improvement +9%, mean difference 3.7 ± 7.1, p < 0.001), but not with the tissue hemoglobin index (THI; mean difference +0.8 ± 10.3, p = 0.428). A high number of worse or unchanged HSI measurements despite successful revascularization was detected. A significant improvement of TcPO2 after revascularization (mean difference +16.2 ± 27.7 mmHg, p < 0.001), consistent with clinical improvement, was detected. No correlation of the HSI parameters with TcPO2 or clinical symptoms could be seen. Conclusions: Significant improvement of StO2, NIR and TcPO2 values was detected after successful revascularization; however, no correlation of HSI parameters with TcPO2 or clinical results could be observed. Furthermore, the substantial rate of lower or unchanged HSI parameters despite clinical improvement and higher TcPO2 values calls the validity and clinical relevance of TIVITA^®-based HSI measurements for postoperative tissue perfusion improvement into question. Full article

Background/Objectives: Chronic limb-threatening ischemia (CLTI) represents the most severe stage of peripheral arterial disease and is associated with high risks of limb loss. Novel approaches are needed for patients who are not candidates for conventional revascularization. This study is to evaluate the clinical efficacy of a venous arterialization-based extracorporeal perfusion technique in patients with CLTI. Methods: A retrospective single-centre, non-randomised comparative cohort study was conducted involving 76 patients with chronic limb-threatening ischemia (CLTI), retrospectively assigned into a perfusion group (n = 38) and a control group (n = 38), with longitudinal pre-/post-treatment assessments at baseline and Day 7 and 6-month limb-salvage follow-up. Patients in the perfusion group received daily extracorporeal perfusion for 6 h over 7 consecutive days. Clinical efficacy was assessed by comparing pre- and post-treatment changes in ankle–brachial index (ABI), transcutaneous oxygen pressure (TcPO₂), skin temperature, wound area, and Visual Analogue Scale (VAS) pain scores. Limb salvage rates were recorded at 6-month follow-up. Results: The perfusion group exhibited significant improvements in ankle–brachial index (ABI) (increase of 0.20 ± 0.02 vs. 0.02 ± 0.01 in the control group, p < 0.001), transcutaneous oxygen pressure (TcPO₂) (increase of 5.24 ± 0.35 mmHg vs. 0.10 ± 0.04 mmHg, p < 0.001), skin temperature (increase of 1.19 ± 0.09 °C vs. 0.02 ± 0.01 °C, p < 0.001), The mean wound healing rate at 7 days was significantly higher in the perfusion group (23.16 ± 2.30%) compared to the control group (5.62 ± 1.23%) (p < 0.001), and Visual Analogue Scale (VAS) score improvement (3.05 ± 1.01 vs. 1.29 ± 0.61, p < 0.001) compared with the control group. The 6-month limb salvage rate was significantly higher in the perfusion group (86.8% vs. 26.3%, p < 0.001), complete wound healing was achieved in 57.9% of the perfusion group versus 10.5% of the control group (p < 0.001). Conclusions: Venous arterialization-based extracorporeal perfusion significantly improves microcirculation and clinical symptoms in CLTI patients and may serve as an effective adjunctive therapy to enhance limb salvage outcomes. Full article

In the current study, we focus on analyzing the relationship between changes in micro- and macrocirculation and different stages of metabolic memory. We hypothesized that early poor glycemic control induces lasting endothelial changes detectable in pediatric type 1 diabetes (T1D) microcirculation. We assessed microcirculation structure and function using capillaroscopy, transcutaneous oxygen pressure (TcPO₂), and optical coherence tomography (OCT). We evaluated macrovascular circulation using pulsatility index (PI), ankle-brachial index (ABI) and pulse pressure (PP). We also examined the relationship between circulation parameters, the age at onset, and diabetes duration. The study included 67 patients with uncomplicated type 1. We divided all patients into four groups based on their HbA_1c levels at T1D onset and their average HbA_1c after one and two years. We assessed the concentrations of TNF-α, IL-35, IL-4, IL-10, IL-18, IL-12, serum angiogenin, VEGF, sVCAM-1, ICAM-1, sP-Selectin, AGEs, and sRAGE. We compared subgroups with different levels of metabolic memory but comparable T1D duration and age at diagnosis. Micro- and macrovascular parameters were similar between the groups. Our comparison of subgroups with identical metabolic memory but different durations and ages at diagnosis revealed clear differences. The subgroup with a shorter T1D duration showed higher capillary density and a smaller inter-capillary distance compared to those with a longer diabetes duration. This subgroup with shorter duration had significantly lower AGE levels and a reduced TNF-α/IL-35 ratio, along with higher levels of IL-35, IL-4, and IL-12, compared to the longer-duration group. Our findings indicate that in youths with uncomplicated T1D, disease duration—not metabolic memory—plays a dominant role in early microvascular alterations. Full article

Background: Transcutaneous PCO₂ (TcPCO₂) effectively represents the partial pressure of carbon dioxide in deep tissues, providing us with more accurate information regarding deep tissue perfusion and oxygen metabolism. Based on this, we aimed to explore the clinical value of TcPCO₂ in assessing free flap blood supply during oral cancer surgery. Methods: A total of 27 patients undergoing oral cancer reconstruction with free flap reconstruction were enrolled. For enrolled patients, continuous monitoring was conducted before, during, and after free flap transplantation surgery. Results: A total of 121 measurements were taken, comprising 93 instances in the normal flap group and 28 instances in the insufficient flap group. The TcPCO₂ levels were significantly higher and transcutaneous PO₂ (TcPO₂) levels were lower in the insufficient group (p < 0.001). The cutoff values for TcPCO₂ and TcPO₂, calculated using the Youden index, were 66 mmHg and 16 mmHg, respectively. TcPCO₂ exhibits high specificity in monitoring the blood supply of free flaps. The area under the ROC curve (AUC) for TcPCO₂ in predicting insufficient flap perfusion was calculated to be 0.912. Conclusions: TcPCO₂ demonstrates high specificity in assessing blood supply in free flaps for patients undergoing oral cancer surgery and has diagnostic significance for early identification of insufficient flap. Full article

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