Pericytes Are Immunoregulatory Cells in Glioma Genesis and Progression.

Vascular co-option is a consequence of the direct interaction between perivascular cells, known as pericytes (PCs), and glioblastoma multiforme (GBM) cells (GBMcs). This process is essential for inducing changes in the pericytes' anti-tumoral and immunoreactive phenotypes. Starting from the initial stages of carcinogenesis in GBM, PCs conditioned by GBMcs undergo proliferation, acquire a pro-tumoral and immunosuppressive phenotype by expressing and secreting immunosuppressive molecules, and significantly hinder the activation of T cells, thereby facilitating tumor growth. Inhibiting the pericyte (PC) conditioning mechanisms in the GBM tumor microenvironment (TME) results in immunological activation and tumor disappearance. This underscores the pivotal role of PCs as a key cell in the TME, responsible for tumor-induced immunosuppression and enabling GBM cells to evade the immune system. Other cells within the TME, such as tumor-associated macrophages (TAMs) and microglia, have also been identified as contributors to this immunomodulation. In this paper, we will review the role of these three cell types in the immunosuppressive properties of the TME. Our conclusion is that the cellular heterogeneity of immunocompetent cells within the TME may lead to the misinterpretation of cellular lineage identification due to different reactive stages and the identification of PCs as TAMs. Consequently, novel therapies could be developed to disrupt GBM-PC interactions and/or PC conditioning through vascular co-option, thereby exposing GBMcs to the immune system.

Assessing health-related quality of life using the Wound-QoL-17 and the Wound-QoL-14-Results of the cross-sectional European HAQOL study using item response theory.

For assessing health-related quality of life in patients with chronic wounds, the Wound-QoL questionnaire has been developed. Two different versions exist: the Wound-QoL-17 and the Wound-QoL-14. For international and cross-cultural comparisons, it is necessary to demonstrate psychometric properties in an international study. Therefore, the aim of this study was to test both questionnaires in a European sample, using item response theory (IRT). Participants were recruited in eight European countries. Item characteristic curves (ICC), item information curves (IIC) and differential item functioning (DIF) were calculated. In both questionnaires, ICCs for most items were well-ordered and sufficiently distinct. For items, in which adjacent response categories were not sufficiently distinct, response options were merged. IICs showed that items on sleep and on pain, on worries as well as on day-to-day and leisure activities had considerably high informational value. In the Wound-QoL-14, the item on social activities showed DIFs regarding the country and age. The same applied for the Wound-QoL-17, in which also the item on stairs showed DIFs regarding age. Our study showed comparable results across both versions of the Wound-QoL. We established a new scoring method, which could be applied in international research projects. For clinical practice, the original scoring can be maintained.

Validation of the Wound-QoL-17 and the Wound-QoL-14 in a European sample of 305 patients with chronic wounds.

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.

How does a chronic wound change a patient's social life? A European survey on social support and social participation.

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.

Pain control with punch grafting in ulcers with underlying arteriolosclerosis.

OBJECTIVE: Martorell hypertensive ischaemic ulcers are often misdiagnosed and can be a clinical and therapeutic challenge. Controversy exists regarding both their underlying triggers and the type of treatment that should be carried out. This study was designed to compare the effectiveness of punch grafting and conventional therapy in pain reduction. METHOD: A single-centre retrospective study was performed, including 40 patients with a clinical diagnosis of a Martorell ulcer or post-traumatic ulcer secondary to arteriolopathy in the elderly, who were treated with punch grafting (n= 24) or conventional medical treatment (n=16). RESULTS: There was a statistically and clinically significant reduction in pain after punch grafting. The minimal overall reduction was of three points in visual analogue pain scores. Of the patients who received punch grafting, 80% reported a VAS pain score of 0 at the third follow-up, in contrast with the 44% (n=4) patients who were treated without punch grafting. The mean time to epithelialisation was 82.1 days in patients who received conventional treatment and 43.5 days in those who received punch grafts. CONCLUSION: Punch grafting is a simple, validated and cost-effective technique that can be performed on an outpatient basis, promotes wound healing and reduces pain. It may control pain and stimulate epithelialisation even if the wound does not present with optimum wound bed characteristics for graft taking. Pain reduction and faster epithelialisation are associated with improvements in patients' quality of life.

Strategies for the Biofunctionalization of Straining Flow Spinning Regenerated Bombyx mori Fibers.

High-performance regenerated silkworm (Bombyx mori) silk fibers can be produced efficiently through the straining flow spinning (SFS) technique. In addition to an enhanced biocompatibility that results from the removal of contaminants during the processing of the material, regenerated silk fibers may be functionalized conveniently by using a range of different strategies. In this work, the possibility of implementing various functionalization techniques is explored, including the production of fluorescent fibers that may be tracked when implanted, the combination of the fibers with enzymes to yield fibers with catalytic properties, and the functionalization of the fibers with cell-adhesion motifs to modulate the adherence of different cell lineages to the material. When considered globally, all these techniques are a strong indication not only of the high versatility offered by the functionalization of regenerated fibers in terms of the different chemistries that can be employed, but also on the wide range of applications that can be covered with these functionalized fibers.

A dual pressure indicator, two-layer compression system for treatment of venous leg ulcers: a review.

OBJECTIVE: Venous leg ulcers (VLUs) are considered the most frequent category of hard-to-heal limb ulcers. Although evidence-based care of VLUs suggests that compression therapy plays a pivotal role in the standard of care, patient adherence is considered low, with at least 33% non-compliance, either due to perceived problems from clinicians regarding their own competency in applying the bandages, or from the patient finding the wrapping bothersome. For many years, four-layer bandaging has been considered the 'gold standard', but application can be difficult and may also prove uncomfortable for patients. Accurate application may be facilitated by a stretch indicator which has been engineered to act as a surrogate for appropriate pressure application that can address the skill concern, while fewer layers can save clinicians' time and improve the quality of life of patients. Here, we review the literature supporting a two-layer system which combines elastic (long stretch) and inelastic (short stretch) components as well as both layers having graphic markers to define that the dressing has been applied at the proper tension. METHOD: An initial search was conducted on PubMed and then followed up by a manual search of Google Scholar to retrieve evidence of different levels, in order to evaluate the outcomes of use of the specific two-layer compression system with pressure indicators in the management of patients presenting with VLUs. RESULTS: A total of four papers discussing the specific compression system in question were identified from 32 publications retrieved from PubMed, while a further six were retrieved from Google Scholar. These 10 publications were considered relevant to the two-layer system and were analysed for the outcomes of care, including wound healing, appropriate application, time-saving and better patient acceptance and adherence. CONCLUSION: Previous authors have demonstrated that two-layer systems are equivalent to four-layer systems. However, the ability to reproducibly apply appropriate compression has remained a question. The papers reviewed demonstrate that evidence suggests that the two-layer compression bandage system with indicators provides continuous, consistent and comfortable treatment that may be easier to apply with accurate pressure levels due to their indicator systems, and therefore, is a procedure that may increase patient adherence and acceptability to the wound therapy.

Refractory palmoplantar pustulosis succesfully treated with apremilast.

Palmoplantar pustulosis is a chronic inflammatory disease which characterized by a eruption of sterile pustules on the palms and soles. Apremilast is an oral phosphodiesterase-4 inhibitor which is approved for the treatment of chronic plaque psoriasis and psoriatic arthritis. However, no clinical trial has been performed to confirm the efficacy of apremilast for palmoplantar pustulosis yet. Moreover, there are very few cases of this disease treated with apremilast. Herein, we describe a case of a refractory palmoplantar pustulosis succesfully treated with apremilast.

Surgical management of middle cranial fossa bone defects: meningoencephalic herniation and cerebrospinal fluid leaks.

Along the medical practice of an Otologist he/she will face middle cranial fossa (MCF) bone defects. The purpose of this study is to contribute to the understanding of this possible life threatening condition, and to share and discuss our management approach. A literature review is also presented. STUDY DESIGN: Retrospective case series at García-Ibáñez Otology and Skull base private center referral. METHODS: This study is based on the analysis of data collected from 19 cases of temporal bone meningoencephalic herniations surgically treated from 2006 to 2018. The follow-up ranged from 18 to 162 months with a mean average of 44.5 months. MAIN FINDINGS: Meningoencephalic herniations were divided into four etiologic groups: spontaneous (24.8%), secondary to chronic otitis media (21.8%), iatrogenic (45.9%), and posttraumatic (7.5%). Different surgical techniques were used as treatment: transmastoid (TM) approach (27.8%), MCF approach (27.8%), combined technique (transmastoid plus minicraniotomy, 3%), and middle ear obliteration with blind sac closure of the external auditory canal (41.4%). CONCLUSIONS: Variables like bilateral hearing level, size and location of the bone defect and existence of CSF leak should be analyzed to select the safest and most effective closing surgical approach.

Punch grafting for pain reduction in hard-to-heal ulcers.

OBJECTIVE: Punch-grafting is a traditional technique to enhance wound healing, which has been associated with significant pain reduction. There are few studies measuring pain reduction after punch grafting, our study was designed to measure this outcome. METHOD: Patients with hard-to-heal wounds treated with punch grafting were included in a single centre prospective study. Wound pain intensity was measured using a Visual Analogue Scale (VAS) at baseline (before the procedure) and at three time points after the procedure. Punch grafting was performed in an outpatient setting. Patient demographic data, wound aetiology and percentage of graft take were recorded. RESULTS: A total of 136 patients were included (62 men and 74 women). Mean age was 60±35 years and 51 (38%) had venous leg ulcers (VLU), 29 (21%) had postoperative wounds, 15 (11%) Martorell ulcers, 15 (11%) traumatic wounds, four (3%) arterial ulcers and 22 (16%) 'other' ulcers. Of the patients, 38 (28%) did not present with painful ulcers and, after punch grafting, all of them remained painless; 29 (21%) patients obtained >70% pain reduction, whereas 73 (54%) patients achieved pain suppression. Pain suppression did not depend on the percentage of graft take. CONCLUSION: Punch-grafting is a simple, technique that not only promotes wound healing but also reduces pain. It can also be performed on an outpatient basis. Further studies should be performed to achieve a better understanding of this beneficial finding. Declaration of interest: The authors have no conflicts of interest to declare.

Preliminary experience of an expert panel using Triangle Wound Assessment for the evaluation of chronic wounds.

OBJECTIVE: Wound assessment is an essential part of wound management and has traditionally focused on the wound bed. The Triangle of Wound Assessment (Triangle) is a new assessment tool that includes a holistic evaluation of the patient with a wound. The aim of this pilot study was to describe the use of the Triangle in our clinical practice in Spain. METHODS: Prospective, consecutive patients, male and female, over 18 years old, with wounds of any aetiology and duration, who attended the centres involved in the study, were recruited between May and June 2017. The TWA was used during the first presentation, to assess the wound bed, edge and periwound skin. The study's expert panel met to discuss the results collected by the assessment, as well as the advantages and disadvantages of the system. RESULTS: We recruited 90 patients. Non-viable tissue (necrotic/sloughy) was recorded in 57.8% of the patients, elevated exudate (medium/high) in 52.2%. Approximately 25% of the patients had signs or symptoms of local infection. Maceration was the most prevalent issue recorded on the wound edge and periwound skin assessment, affecting 31.1% and 30.0% of the patients, respectively. The presence of hyperkeratosis was high for the study population as the main aeitologies of the wounds identified here were DFU. CONCLUSIONS: The implementation of Triangle Wound Assessment could help in the holistic approach to patient care by focusing on more than local wound care, identifying barriers to achieving wound healing and evaluating wound response and patient compliance.

Validity and feasibility of the wound-QoL questionnaire on health-related quality of life in chronic wounds.

Chronic wounds have a major socioeconomic impact due to their frequency, chronicity, and societal costs. Patients experience substantial quality of life (QoL) impairments. The use of questionnaires for a continuous assessment of QoL and resulting interventions to improve the situation of the individual are an important cornerstone of a guideline-based wound care. The aim of this study was to investigate the validity of the Wound-QoL questionnaire. Patients with chronic wounds from two different centers were included in the prospective study. All patients completed the Wound-QoL and two other QoL questionnaires (European Quality of Life-5 Dimensions, EQ-5D, and Freiburg Life Quality Assessment for wounds, FLQA-wk) at baseline and at two more time points (4 and 8 weeks, respectively). Wound status was defined with an anchor question. Two hundred and twenty-seven patients (48.5% women) participated in the study. Mean age was 66.9 years (range 17-96, median 69.5). Indications were venous leg ulcers (40.1%), pyoderma gangraenosum (14.1%), diabetic or ischemic foot ulcers (5.3%), pressure ulcers (2.6%), and other etiologies (30.0%). The Wound-QoL showed good internal consistency, with high Cronbach's alpha in all the subscales and in the global scale in all time points (>0.8). Convergent validity was satisfactory since there were significantly (p ≤ 0.001) good correlations with the EQ-5D (range = 0.5-0.7) and FLQA-wk global score (r > 0.8) at every time point. Responsiveness was high, too. The Wound-QoL is a simple, valid tool for the longitudinal assessment of QoL in patients with chronic wounds. This questionnaire is suitable for use in clinical trials, quality of care studies and clinical routine.

Neuropathic ulcers in leprosy treated with intralesional platelet-rich plasma.

Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy. Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) may restore the healing process, leading to a reparative phase. We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. PRP therapy has been growing as a viable treatment alternative for chronic ulcers. However, stronger scientific evidence is required to support its potential benefit for use in chronic wounds.