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A limited understanding of the pathology underlying chronic wounds has hindered the development of effective diagnostic markers and pharmaceutical interventions. This study aimed to elucidate the molecular composition of various common chronic ulcer types to facilitate drug discovery strategies. We conducted a comprehensive analysis of leg ulcers (LUs), encompassing venous and arterial ulcers, foot ulcers (FUs), pressure ulcers (PUs), and compared them with surgical wound healing complications (WHCs). To explore the pathophysiological mechanisms and identify similarities or differences within wounds, we dissected wounds into distinct subregions, including the wound bed, border, and peri-wound areas, and compared them against intact skin. By correlating histopathology, RNA sequencing (RNA-Seq), and immunohistochemistry (IHC), we identified unique genes, pathways, and cell type abundance patterns in each wound type and subregion. These correlations aim to aid clinicians in selecting targeted treatment options and informing the design of future preclinical and clinical studies in wound healing. Notably, specific genes, such as PITX1 and UPP1, exhibited exclusive upregulation in LUs and FUs, potentially offering significant benefits to specialists in limb preservation and clinical treatment decisions. In contrast, comparisons between different wound subregions, regardless of wound type, revealed distinct expression profiles. The pleiotropic chemokine-like ligand GPR15L (C10orf99) and transmembrane serine proteases TMPRSS11A/D were significantly upregulated in wound border subregions. Interestingly, WHCs exhibited a nearly identical transcriptome to PUs, indicating clinical relevance. Histological examination revealed blood vessel occlusions with impaired angiogenesis in chronic wounds, alongside elevated expression of genes and immunoreactive markers related to blood vessel and lymphatic epithelial cells in wound bed subregions. Additionally, inflammatory and epithelial markers indicated heightened inflammatory responses in wound bed and border subregions and reduced wound bed epithelialization. In summary, chronic wounds from diverse anatomical sites share common aspects of wound pathophysiology but also exhibit distinct molecular differences. These unique molecular characteristics present promising opportunities for drug discovery and treatment, particularly for patients suffering from chronic wounds. The identified diagnostic markers hold the potential to enhance preclinical and clinical trials in the field of wound healing.
The Wound-QoL assesses the impact of chronic wounds on patients' health-related quality of life (HRQoL). A 17-item and a shortened 14-item version are available. The Wound-QoL-17 has been validated for multiple languages. For the Wound-QoL-14, psychometric properties beyond internal consistency were lacking. We aimed to validate both Wound-QoL versions for international samples representing a broad range of European countries, including countries for which validation data had yet been pending. Patients with chronic wounds of any aetiology or location were recruited in Austria, Lithuania, the Netherlands, Poland, Slovakia, Spain, Switzerland and Ukraine. Psychometric properties were determined for both Wound-QoL versions for the overall sample and, if feasible, country-wise. We included 305 patients (age 68.5 years; 52.8% males). Internal consistency was high in both Wound-QoL-17 (Cronbach's α: 0.820–0.933) and Wound-QoL-14 (0.779–0.925). Test–retest reliability was moderate to good (intraclass correlation coefficient: 0.618–0.808). For Wound-QoL-17 and Wound-QoL-14, convergent validity analyses showed highest correlations with global HRQoL rating (r = 0.765; r = 0.751) and DLQI total score (r = 0.684; r = 0.681). Regarding clinical data, correlations were largest with odour (r = −0.371; r = −0.388) and wound size (r = 0.381; r = 0.383). Country-wise results were similar. Both Wound-QoL versions are valid to assess HRQoL of patients with chronic wounds. Due to its psychometric properties and brevity, the Wound-QoL-14 might be preferrable in clinical practice where time is rare. The availability of various language versions allows for the use of this questionnaire in international studies and in clinical practice when foreign language patients are being treated.
Chronic wounds can severely limit patient's social life. This cross-sectional study investigated quantitatively social support of patients with chronic wounds, its association with health-related quality of life as well as qualitatively changes in social participation of these patients. Overall, 263 patients from seven countries participated. The most frequent wound class was leg ulcer (49.2%). Results revealed generally high levels of social support (mean global score: 5.5) as measured with the Multidimensional Scale of Perceived Social Support. However, individuals differed considerably (range 1.0–7.0). All dimensions of social support differed by patients' family and living situations (p < 0.001 to p = 0.040) and were positively correlated with generic health-related quality of life (r = 0.136–0.172). Having children, living with others and being in a relationship were significant predictors of having higher global social support. Patients reported great support from family members. Many participants reported no changes in relationships with friends. Wound care managers took an important role and provided additional emotional support. Patients reported a range of discontinued activities. Despite the high overall level of social support, inter-individual differences should be acknowledged. The importance of family carers should be acknowledged to be able to reduce caregiver burden and to ensure high-qualitative wound care.
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