The impact of obesity on chronic oedema/lymphoedema of the leg - an international multicenter cross-sectional study (LIMPRINT).

BACKGROUND/OBJECTIVES: Obesity and chronic oedema/lymphoedema are two distinct but related conditions, rarely investigated together. The aim was to study the impact of increased weight on chronic oedema and related factors. SUBJECTS/METHODS: A cross-sectional study, 38 centers, nine countries. Patients with clinically confirmed chronic oedema/lymphoedema of the leg were included. Weight category was estimated as: normal weight (BMI 20-30), class I-II obesity (BMI 30-40), or class III obesity (BMI > 40). Factors were tested for an association with increased weight, using a multivariable model. RESULTS: A total of 7397 patients were included; 43% with normal weight, 36% class I-II obesity and 21% class III obesity. Increased weight was associated with more advanced stages of chronic oedema (ISL stage III; the most advanced form); affecting 14% in normal weight, 18% class I-II obesity and 39% class III obesity (p < 0.001). Ten factors were independently associated with increased weight: diabetes (OR 2.4), secondary lymphoedema (OR 2.7), cellulitis/erysipelas within 12 months (OR 1.2), bilateral lymphoedema (OR 3.6), compression therapy (OR 2.1), increased swelling duration (1-2 years OR 1.3, 2-5 years OR 2.5, 5-10 years OR 3.6, >10 years OR 3.5) decreased mobility (walking with aid OR 1.9, being chair bound OR 1.2) and age (reference<45 years; 45-64 years OR 1.5, 75-84 years OR 0.6, 85+ years OR 0.2). Increased weight was associated with a lower presentation of peripheral arterial disease (OR 0.7) and poorer chronic oedema control (OR 0.8). Patients with obesity had lower function, appearance and more severe symptoms (LYMQOL) and lower quality of life (EuroQol). CONCLUSIONS: Obesity negatively impacts chronic oedema, leading to more advanced stages. Achieving good control of swelling with compression is more difficult in these patients. Increased awareness of chronic oedema/lymphoedema as a complication of obesity is important for early detection and for developing effective strategies to prevent and manage them.

Prevalence and characteristics of pain in patients with lower-extremity ulcers-A cross-sectional study.

The study aimed to investigate the prevalence and characteristics of pain in different ulcer types and to identify factors associated with pain experience in patients with lower-extremity ulcers. A cross-sectional single-centre study was performed, including 130 newly referred outpatients with lower-extremity ulcers. Pain intensity was measured with a visual analog scale (VAS) and pain characteristics with the short form mcgill pain questionnaire-2 (SF-MPQ-2). The mean pain intensity was 29.5 (SD 31.8) at rest and 35.5 (SD 34.1) during movement (0-100 VAS). 61.5% of the patients experienced pain (VAS > 0) at rest and 70.8% during movement. Moderate to severe pain at rest was seen in 39.2% and in 43.8% of patients during movement. The mean total score on SF-MPQ-2 (range 0-220) was 35.9 (SD 32.6). Most of the patients described pain as intermittent (mean 11.8 SD 13.9). Analgesics were prescribed for 78% of the patients. Ulcer type (i.e., arterial, immunological, pressure and venous) and age were associated with pain severity, and women had a significantly lower well-being score than men. Prevalence of pain in patients with lower-extremity ulcers was high across different ulcer aetiologies. Pain intensity and quality must be assessed to obtain adequate pain management.

Factors associated with cellulitis in lymphoedema of the arm - an international cross-sectional study (LIMPRINT).

BACKGROUND: Lymphoedema is a globally neglected health care problem and a common complication following breast cancer treatment. Lymphoedema is a well-known predisposing factor for cellulitis, but few have investigated the risk factors for cellulitis in this patient cohort on an international level. The aim of this study was to identify the frequency of cellulitis in patients with lymphoedema of the arm, including potential risk factors for cellulitis. METHODS: An international, multi-centre, cross-sectional study including patients with clinically assessed arm lymphoedema. The primary outcome was the incidence of cellulitis located to the arm with lymphoedema within the last 12 months, and its potential associated risk factors. The secondary outcome was life-time prevalence of cellulitis. Adults with clinically-assessed arm lymphoedema/chronic oedema (all causes) and able to give informed consent were included. End-of-life-patients or those judged as not in the patient's best interest were excluded. Both univariable and multivariable analysis were performed. RESULTS: A total of 2160 patients were included from Australia, Denmark, France, Ireland, Italy, Japan, Turkey and United Kingdom. Secondary lymphoedema was present in 98% of the patients; 95% of these were judged as related to cancer or its treatment. The lifetime prevalence of cellulitis was 22% and 1-year incidence 11%. Following multivariable analysis, factors associated with recent cellulitis were longer swelling duration and having poorly controlled lymphoedema. Compared to having lymphoedema less than 1 year, the risk increased with duration: 1-2 years (OR 2.15), 2-5 years (OR 2.86), 5-10 years (OR 3.15). Patients with well-controlled lymphoedema had a 46% lower risk of cellulitis (OR 0.54, 95% CI 0.39-0.73, p < 0.001). More advanced stages of lymphoedema were associated with cellulitis even after adjustment for swelling duration and control of swelling by logistic regression (stage II OR 5.44, stage III OR 9.13, p = 0.002), demonstrated in a subgroup analysis. CONCLUSION: Patients with advanced arm lymphoedema are at particular risk of developing cellulitis. Prevention of lymphoedema progression is crucial. The results lend towards a positive effect of having well-treated lymphoedema on the frequency of cellulitis.

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.

A simplified method for monitoring cytokines in wound fluid.

Cytokines in wound fluid are used as surrogates for wound healing in clinical research. The current methods used to collect and process wound fluid are noninvasive but not optimal. The aim of this prospective study was to evaluate a method (NovaSwab) by which wound fluid is collected by a surface swab and eluted in a physiological buffer for subsequent cytokine analysis. Wound fluid from 12 patients with leg ulcers was assessed by NovaSwab at the start (Day 0) and at the end of a 23-h collection period of wound fluid retained by foam oblates beneath an occlusive film dressing (Day 1). GM-CSF, IL-1α, IL-1ß, IL-6, IL-8, PDGF-AA, TNF-α and VEGF levels were measured by multiplex and electrochemiluminescence assays. IL-1α (2.4×), IL-1ß (2.0×) and IL-8 (1.8×) levels increased from Day 0 to Day 1 as detected by NovaSwab, indicating local production of these polypeptides in the wounds. On Day 1, the NovaSwab method yielded higher levels of IL-1α (4.0×), IL-1ß (2.7×) and IL-6 (2.7×), and 35% lower levels of VEGF than those in wound fluid accumulated for 23 h in foam oblates (on average, 5 ml of wound fluid). In vitro experiments showed that the investigated cytokines in cell-free wound fluid were recovered in a quantitative manner by the NovaSwab method. We conclude that the method presented here is a promising research tool to study the kinetics of soluble cytokines over the course of wound healing. More studies are needed to determine the interobserver variation and reproducibility of the NovaSwab method.

Wounds in chronic leg oedema.

Wounds and chronic oedema are common disorders, but rarely studied together. The objective of this cross-sectional study was to investigate the point-prevalence and risk factors of wounds on the leg, in chronic leg oedema. Forty sites in nine countries were included. Of 7077 patients with chronic leg oedema, 12.70% had wounds. Independent risk factors were: peripheral arterial disease (odds ratio (OR) 4.87, 95% confidence intervals (CI) 3.63-6.52), cellulitis within the past 12 months (OR 2.69, 95% CI 2.25-3.21), secondary lymphoedema (OR 2.64, 95% CI 1.93-3.60), being male (OR 2.08, 95% CI 1.78-2.44), being over 85 years of age (OR 1.80, 95% CI 1.23-2.62), underweight (OR 1.79, 95% CI 1.14-2.79), bed bound (OR 1.79, 95% CI 1.01-3.16), chair bound (OR 1.52, 95% CI 1.18-1.97), diabetes (OR 1.47, 95% CI 1.23-1.77), and walking with aid (OR 1·41, 95% CI 1.17-1.69). 43.22% of those with wounds had clinically defined well-controlled oedema, associated with a significantly lower risk of wounds (OR 0.50, 95% CI 0.42-0.58, P < .001). Hard/fibrotic tissue (OR 1.71, 95% CI 1.19-2.48), and a positive Stemmers sign (OR 1.57, 95% CI 1.05-2.35) were associated with wounds. The study reinforces the importance of measures to control oedema, as controlled swelling was associated with a 50% lower risk of wounds.

[Research trends in wound care].

Advanced wound care strategies are emerging, but more robust clinical data are needed such as identification of precise biomarkers for point-of-care diagnostics and 24/7 data. This will aid in the implementation of effective therapies in relevant patients. Increased knowledge among health care providers, health literacy improvement as well as patient involvement are also important in this process. In this review we focus on current research trends in compression therapy, modulation of inflammation and growth factors, the proteolytic microenvironment and microbiology.

Lipoedema.

Lipoedema is an overlooked and often misdiagnosed condition, which mainly affects women. This review summarises the present knowledge of the condition. It is characterised by bilateral and symmetrical accumulation of subcutaneous adipose tissue mainly in the legs. Patients with lipoedema often display tenderness to palpation or spontaneous pain in the adipose tissue. Lipoedema is diagnosed based on the medical history and clinical findings. Treatment includes conservative and surgical options with the aim of relieving symptoms and increasing mobility, but there is a paucity of randomised controlled trials.

Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study.

INTRODUCTION: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment. METHODS AND ANALYSIS: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis. ETHICS AND DISSEMINATION: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.

[Pyoderma gangrenosum].

Pyoderma gangrenosum is a diagnostic and therapeutic challenge. A misdiagnosis or delayed diagnosis can lead to increased morbidity and death. A fast workup and initiation of treatment is essential. In this review, we present new diagnostic criteria, which can ease the diagnosis, and we summarise the evidence of different treatment modalities. The evidence points towards local immunosuppressive treatment in mild disease, supplemented by systemic glucorticosteroids, ciclosporin or tumour necrosis factor-alpha inhibitors in severe cases. Other biologics are emerging.