Topical oxygen therapy and singlet oxygen in wound healing: A scoping review.

The aim of this scoping review was to provide an overview of current research into topical oxygen therapies including the under-researched singlet oxygen for wound healing. A scoping review was undertaken using five databases. After duplicates and ineligible studies were excluded, 49 studies were included for a narrative review. Out of the included 49 studies, 45 (91.8%) were published in the past 10 years (2013-2023) with 32 (65.3%) published in the past 5 years (2018-2023). Eight of the studies were systematic reviews and/or meta-analysis and 18 were RCTs. The search identified zero human RCTs on singlet oxygen, but one human cohort study and five studies in animals. There is evidence that topical oxygen therapy may be useful for the treatment of chronic wounds, mainly diabetic foot ulcers. Singlet oxygen has shown potential, but would need further confirmation in controlled human trials, including more research to understand the bio-properties.

Signaling via a CD28/CD40 chimeric costimulatory antigen receptor (CoStAR™), targeting folate receptor alpha, enhances T cell activity and augments tumor reactivity of tumor infiltrating lymphocytes.

Transfer of autologous tumor infiltrating lymphocytes (TIL) to patients with refractory melanoma has shown clinical efficacy in a number of trials. However, extending the clinical benefit to patients with other cancers poses a challenge. Inefficient costimulation in the tumor microenvironment can lead to T cell anergy and exhaustion resulting in poor anti-tumor activity. Here, we describe a chimeric costimulatory antigen receptor (CoStAR) comprised of FRα-specific scFv linked to CD28 and CD40 intracellular signaling domains. CoStAR signaling alone does not activate T cells, while the combination of TCR and CoStAR signaling enhances T cell activity resulting in less differentiated T cells, and augmentation of T cell effector functions, including cytokine secretion and cytotoxicity. CoStAR activity resulted in superior T cell proliferation, even in the absence of exogenous IL-2. Using an in vivo transplantable tumor model, CoStAR was shown to improve T cell survival after transfer, enhanced control of tumor growth, and improved host survival. CoStAR could be reliably engineered into TIL from multiple tumor indications and augmented TIL activity against autologous tumor targets both in vitro and in vivo. CoStAR thus represents a general approach to improving TIL therapy with synthetic costimulation.

Comparison of Restenosis Risk in Single-Layer versus Dual-Layer Carotid Stents: A Duplex Ultrasound Evaluation.

PURPOSE: The aim of this study was to report intermediate-term results of duplex ultrasound follow-up of carotid artery stenting performed with the dual-layer stent as compared to concurrent patients treated with other commercially available single-layer carotid stents. MATERIALS AND METHODS: A single centre, retrospective, nonrandomized study including 162 non-consecutive patients with 199 implanted carotid stents treated over a 7-year period was conducted. Patients with at least one ultrasound examination after treatment were included. Procedural and follow-up data for patients treated with the dual-layer stent implantation (83 stents) vs first-generation carotid stents implantations (116 stents) were compared. RESULTS: The median follow-up time was 24.0 months (IQR 10-32 months) for dual-layer stents and 27.5 months (IQR 10.3-59 months) for single-layer stents. The rate of severe restenosis was significantly higher in the dual-layer stent group than in the single-layer group (13.3% [11/83] vs 3.4% [4/116], p = 0.01). Seven reinterventions were performed in 5 patients with dual-layer stents. The rate of reintervention was significantly higher compared to no reinterventions in single-layer stents (6% [5/83] vs 0% [0/116], p = 0.012). Patients with restenosis had significantly higher presence of dyslipidaemia (100% [12/12] vs 63.3% [95/150], p = 0.009). CONCLUSIONS: In this real-world cohort of patients undergoing carotid artery stenting, the patients treated with low-profile dual-layer micromesh stent showed higher rates of restenosis and reinterventions compared to first-generation single-layer stents.

"I Cry. I Simply Cry." An Ethnography of a Lymphedema Summer Camp.

Background: The aim of this study was to explore how self-management is taught, learnt, and experienced during a 3-day educational Lymphedema Camp for parents of children with lymphedema. Methods: Participants (professionals, parents, and children) were observed during camp activities and interviewed informally and formally in focus groups. The embodied nature of the experience expressed by professionals, parents, and researchers became the analytical focus for understanding the felt tensions in the teaching and learning of self-management to families. Findings: The affective sensibilities associated with the uncertainties involved in teaching and learning self-management skills were palpable given that: young people are now expected to take up strict time-consuming self-management regimens (often via the support of a parent) where "evidence-based" outcomes are uncertain or may not match the outcomes wanted by a young person (varying in age and therefore ability or willingness to engage); or where there are tensions within the family; and the variety of different professionals involved means that techniques varied but where these professionals also lacked the necessary skills training to guide them in how to teach self-management. An analytical focus on the distress, doubt, fear, loneliness, guilt, and moralism felt by professionals, parents, and the researchers supports us to identify the character of the problems associated with performing best practice care guidance where there is a lack of practical support or resources for how self-management in this population should be achieved. Conclusion: To avoid these issues more training and research are needed on "how" to self-manage and stop victim-blaming that generates tensions and drives a wedge between the carer and the cared-for. When systemic problems get located with individuals (professionals, parents, or children), this directs our attention and understanding away from systems of care that lack coordination, may be under-resourced, and where effective training is absent.

Factors Predicting Limb Volume Reduction Using Compression Bandaging Within Decongestive Lymphatic Therapy in Lymphedema: A Multicountry Prospective Study.

Objectives: To identify predictive factors associated with limb volume reduction using different decongestive lymphatic therapy (DLT) systems in patients with lymphoedema, over a period of up to 28 days. Methods: A multicountry (Canada, France, Germany, the United Kingdom) prospective cohort study using (DLT): skin care, exercise, compression bandaging, and manual lymphatic drainage for up to 4 weeks. Reduction in limb volume comparing DLT with (1) standard multilayer bandaging with inelastic material, and with (2) multilayer bandaging with Coban2, together with the identification of factors associated with limb volume changes. Results: Out of 264 patients with upper or lower limb lymphedema, 133 used Coban2 and 131 used standard care. Following DLT, mean limb volume reduction was 941 mL using Coban2 compared with 814 mL using standard care. A difference of 127 mL was found (95% confidence interval -275 to 529 mL, p = 0.53). Of the 176 patients with leg swelling, 166 (94.3%) had a limb volume measurement after 28 days and were included in the risk factor analysis. Of these, 132 (79.5%) were female, with overall mean age of 60.1 years (standard deviation = 14.7), with secondary lymphedema in 102/163 (62.6%). Duration of lymphedema was >10 years in 75/161 (46.6%) and 99/166 (59.7%) were International Society of Lymphology late-stage II/III, indicating longstanding and/or a high frequency of patients with advanced stages of lymphedema. Ninety-one (54.8%) received Coban2 and 75 (45.2%) had standard care. Multivariable factors for a greater leg volume reduction were large initial leg volume (p < 0.001), DLT treatment duration of 4 weeks compared with 2 weeks (p = 0.01), and peripheral arterial disease (p = 0.015). Conclusion: Limb volume changes were found to be similar between groups. Lack of standardization of DLT makes interpretation of effectiveness problematic. There is an urgent need for randomized-controlled trials. Despite this, severe lymphedema with a large limb volume responded well to DLT in this study.

Percutaneous thrombectomy in the management of early rethrombosis in venous thoracic outlet syndrome: two case reports.

BACKGROUND: Venous thoracic outlet syndrome resulting in the upper limb deep venous thrombosis is known as Paget-Schroetter syndrome or effort thrombosis. A general treatment algorithm includes catheter-directed thrombolysis followed by surgical thoracic outlet decompression. There are limited data regarding endovascular treatment of rethrombosis presenting early after the surgery. CASE PRESENTATION: Two cases of early rethrombosis successfully treated with percutaneous mechanical thrombectomy by two different techniques are described. In both cases, rethrombosis was diagnosed soon after thrombolysis and first rib resection with scalenectomy. After 12 months, both patients remain symptom-free, with patent subclavian veins confirmed by duplex ultrasonography. CONCLUSION: Percutaneous mechanical thrombectomy devices may offer a safe treatment option for patients with recurrent thrombosis after thoracic outlet surgery, even when thrombolytic therapy is contraindicated.

Prevalence and Risk Factors for Chronic Edema in U.K. Community Nursing Services.

Background and Study Design: Chronic edema (CO) is believed to be a major clinical problem within community nursing services in the United Kingdom. This study was undertaken as part of the LIMPRINT international study to determine the number of people with CO and its impact on health services. Methods and Results: Three urban-based community nursing services participated in the United Kingdom with prospective evaluation for 4 weeks of all patients receiving nursing care using a questionnaire-based interview and clinical assessment using the LIMPRINT tools. Of the total 2541 patients assessed, 1440 (56.7%) were considered to have CO, comprising Leicester City [768/1298 (59.2%)], Nottingham West [124/181 (68.5%)], and Nottingham City [548/1062 (51.6%)]. The mean age for women with CO was 78.6 (standard deviation [SD] 12.8) years and that for men with CO was 72.9 (SD 14.5). More patients with CO suffered from diabetes (32.1% vs. 27.9%, p = 0.027), heart failure/ischemic heart disease (27.3% vs. 14.0%, p < 0.001), and peripheral arterial occlusive disease (5.5% vs. 1.9%, p < 0.001). By far the greatest association was with the presence of a wound (73.6% vs. 37.9%, p < 0.001). Cellulitis affected 628 patients (24.7%) and 688 patients (47.8%) had a concurrent leg ulcer. Rates of reduced mobility (71.6% vs. 61.9%) and obesity were higher in those with CO. Six independent factors associated with CO were service location, age, ethnicity, obesity, heart failure, and the presence of a wound. Conclusion: CO is a major and growing health care problem within primary care that has been previously unrecognized and requires effective service provision.

Clinical and Ethical Challenges in Undertaking LIMPRINT in Vulnerable Populations.

Background and Study Objective: To estimate the prevalence of chronic edema (CO) and wounds within two vulnerable populations, a male high security prison in the East Midlands (United Kingdom) and residential and nursing homes in the United Kingdom and Australia. Methods and Results: Methods for screening for CO and wounds were adapted from the main LIMPRINT methodology. Prison Population: In total, 195 inmates were recruited with 22 (11%) having CO. While the majority were white Caucasian (156/83.4%) a further 20 (10.7%) were dark skinned with 11 (5.95%) from other minority populations. Comorbidities included 123 (63%) smokers, 22 (11%) alcohol dependant, 60 (31%) with mental health problems, and 35 (18%) a history of self-harm. Only three had a current wound with 30 (16%) having had a traumatic stab wound. Residential and Nursing Homes (United Kingdom and Australia): In the United Kingdom, the total population available for inclusion was 189 with only 137 (73%) recruited. Seventy-two of the 137 (52%) suffered from CO and a further 16 (23%) had a history of cellulitis. Results from the Australian residential care facilities have been published in full. In summary, of the 37 participants 20 (54%) experienced CO with 25 (68%) having comorbidities and 11 (30%) having a concurrent wound. Conclusion: Obtaining an accurate picture of the prevalence and impact of CO in vulnerable populations is extremely challenging due to issues of access and consent. Lack of reliable data for these populations will contribute to poor service provision.

LIMPRINT: Estimation of the Prevalence of Lymphoedema/Chronic Oedema in Acute Hospital in In-Patients.

Background: To estimate the prevalence of lymphedema/chronic edema (CO) and wounds in acute hospital inpatients in five different countries. Methods and Results: A point-prevalence study was carried out during working day periods in six general hospitals in four countries (Denmark, France, United Kingdom, and Australia) and one hospital oncology inpatient unit in one other country (Ireland). The study used validated clinical tools for the assessment and collection of data. Data were collected by expert clinicians through interviews and physical examination of the patients present in the wards. A total of 1905 patients could be included and investigated among the 3041 total bed occupancy in the seven hospitals. Lymphedema/CO was present in 723 of them (38%). Main risk factors associated with CO were age, morbid obesity, and heart failure, as well as chair bound immobility and neurological deficiency. History of cellulitis was frequent in patients with CO and wounds (24.8%) and CO alone (14.1%) compared to the 1.5% prevalence in patients without CO. Conclusion: Lymphedema/CO is very frequent in patients hospitalized in hospital acute wards. It is strongly associated with obesity, venous insufficiency, and heart failure. Our results strongly suggest a hidden health care burden and cost linked to CO independently of chronic wounds.

LIMPRINT: The UK Experience-Subjective Control of Swelling in Patients Attending Specialist Lymphedema Services.

Background and Study Design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic edema (CO) and its impact on health services. Overall 7436 with CO were recruited in the main UK study from a range of health settings. Methods and Results: Factors relating to subjective control of arm and leg CO were defined in the UK. A total of 1565 patients were included in the study with exclusions for: no limb swelling or not recorded (1669), having concurrent arm/leg CO (272), control of assessment missing (5) and professional being unsure of control status of CO (325). Arm swelling occurred in 953 (18.5%) with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.2%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were : obesity, neurological disease and cellulitis in the last year and for leg CO, obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialized centers is complex due to sociodemographic and clinical comorbidities.

Multiplexed profiling of RNA and protein expression signatures in individual cells using flow or mass cytometry.

Advances in single-cell analysis technologies are providing novel insights into phenotypic and functional heterogeneity within seemingly identical cell populations. RNA within single cells can be analyzed using unbiased sequencing protocols or through more targeted approaches using in situ hybridization (ISH). The proximity ligation assay for RNA (PLAYR) approach is a sensitive and high-throughput technique that relies on in situ and proximal ligation to measure at least 27 specific RNAs by flow or mass cytometry. We provide detailed instructions for combining this technique with antibody-based detection of surface/internal protein, allowing simultaneous highly multiplexed profiling of RNA and protein expression at single-cell resolution. PLAYR overcomes limitations on multiplexing seen in previous branching DNA-based RNA detection techniques by integration of a transcript-specific oligonucleotide sequence within a rolling-circle amplification (RCA). This unique transcript-associated sequence can then be detected by heavy metal (for mass cytometry)- or fluorophore (for flow cytometry)-conjugated complementary detection oligonucleotides. Included in this protocol is methodology to label oligonucleotides with lanthanide metals for use in mass cytometry. When analyzed by mass cytometry, up to 40 variables (with scope for future expansion) can be measured simultaneously. We used the described protocol to demonstrate intraclonal heterogeneity within primary cells from chronic lymphocytic leukemia patients, but it can be adapted to other primary cells or cell lines in suspension. This robust, reliable and reproducible protocol can be completed in 2-3 d and can be paused at several stages for convenience.