Pressure ulcers microbiota dynamics and wound evolution.
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ABSTRACT:
SUBMITTER: Dunyach-Remy C
PROVIDER: S-EPMC8445962 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Label‑free quantitative mass spectrometry was used to analyze the differences in the granulation tissue protein expression profiles of patients with diabetic foot ulcers (DFUs) before and after negative‑pressure wound therapy (NPWT) to understand how NPWT promotes the healing of diabetic foot wounds. A total of three patients with DFUs hospitalized for Wagner grade 3 were enrolled. The patients received NPWT for one week. The granulation tissue samples of the patients prior to and following NPWT for one week were collected. The protein expression profiles were analyzed with label‑free quantitative mass spectrometry and the differentially expressed proteins (DEPs) in the DFU patients prior to and following NPWT for one week were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to annotate the DEPs and DEP‑associated signaling pathways. Western blotting and ELISA were performed to validate the results. By comparing the differences in the protein profiles of granulation tissue samples prior to and following NPWT for one week, 36 proteins with significant differences were identified (P<0.05); 33 of these proteins were upregulated and three proteins were downregulated. NPWT altered proteins mainly associated with antioxidation and detoxification, the cytoskeleton, regulation of the inflammatory response, complement and coagulation cascades and lipid metabolism. The functional validation of the DEPs demonstrated that the levels of cathepsin S in peripheral blood and granulation tissue were significantly lower than those prior to NPWT (P<0.05), while the levels of protein S isoform 1, inter α‑trypsin inhibitor heavy chain H4 and peroxiredoxin‑2 in peripheral blood and granulation tissue were significantly higher than those prior to NPWT (P<0.05). The present study identified multiple novel proteins altered by NPWT and laid a foundation for further studies investigating the mechanism of action of NPWT.
| S-EPMC8503750 | biostudies-literature
Project description:The ischemia-reperfusion (I/R) induced skin lesion has been identified as primary cause of pressure ulcer. Better understanding of the mechanism is required for new therapy development. Leucine rich repeat containing protein 19 (LRRC19) is a recently discovered transmembrane protein containing leucine-rich repeats and plays a role in immune response. To investigate the role of LRRC19 in pressure ulcers, mouse ulcer model was established with two cycles of I/R. The expression of LRRC19 was assessed during injury. siRNA mediated LRRC19 downregulation was applied to investigate the disease severity, immune cell infiltration and pro-inflammatory cytokines production. The primary skin fibroblasts were stimulated with IL-1β to dissect the molecular mechanism. LRRC19 was readily induced in I/R induced lesion site in a pattern mimicking the disease progress as measured by wound area. Knockdown of LRRC19 by siRNA significantly alleviated the disease severity and attenuated immune cell infiltration and pro-inflammatory cytokines production. In primary skin fibroblast model, siRNA knockdown of LRRC19 suppressed IL-1β mediated NFκB activation and its downstream cytokines production. LRRC19 was a novel factor for I/R-induced tissue damage by promoting NFκB dependent pro-inflammatory response. Our results supported that LRRC19 could be a potential therapeutic target for pressure ulcers.
| S-EPMC6150054 | biostudies-literature
Project description:Imaging mass spectrometry (IMS) was employed for the analysis of frozen skin biopsies to investigate the differences between stage IV pressure ulcers that remain stalled, stagnant, and unhealed versus those exhibiting clinical and histological signs of improvement. Our data reveal a rich diversity of proteins that are dynamically modulated, and we selectively highlight a family of calcium binding proteins (S-100 molecules) including calcyclin (S100-A6), calgranulins A (S100-A8) and B (S100-A9), and calgizzarin (S100-A11). IMS allowed us to target three discrete regions of interest: the wound bed, adjacent dermis, and hypertrophic epidermis. Plots derived using unsupervised principal component analysis of the global protein signatures within these three spatial niches indicate that these data from wound signatures have potential as a prognostic tool since they appear to delineate wounds that are favorably responding to therapeutic interventions versus those that remain stagnant or intractable in their healing status. Our discovery-based approach with IMS augments current knowledge of the molecular signatures within pressure ulcers while providing a rationale for a focused examination of the role of calcium modulators within the context of impaired wound healing.
| S-EPMC4324443 | biostudies-literature
Project description:Visual and empirical assessments do not enable the early detection of wound deterioration or necroses. No suitable objective indicator for predicting poor wound-healing is currently available. We used infrared thermography to determine the association between wound temperature and pressure-wound healing. We examined patients with grades 2-4 pressure ulcers from a medical center in southern Taiwan and recorded the temperatures of the wound bed, periwound, and normal skin using infrared thermographic cameras. A total of 50 pressure ulcers and 248 infrared-thermography temperature records were analyzed. Normal skin temperature was not related to pressure ulcer wound healing. In a multivariate analysis, higher malnutrition universal-screening-tool scores were associated with poor wound-healing (p = 0.020), and higher periwound-temperature values were associated with better wound-healing (p = 0.028). In patients who had higher periwound-skin temperature than that of the wound bed, that result was also associated with better wound-healing (p = 0.002). Wound-bed and periwound temperatures differed significantly with the grade of the pressure ulcer, and a high periwound temperature was positively correlated with wound healing. Infrared thermography can objectively serve as indicators for assessing pressure-ulcer healing.
| S-EPMC8269037 | biostudies-literature
Project description:BackgroundNegative pressure wound therapy (NPWT) is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial.MethodsThis was a two-centre (acute and community), pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC) (spun hydrocolloid, alginate or foam dressings). Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up.ResultsThree hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8%) were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group) during follow-up (time to healing 79 days). The mean number of treatment visits per week was 3.1 (NPWT) and 5.7 (SC); 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT) and 5.0 (SC) months.ConclusionsThis pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial.Trial registrationCurrent Controlled Trials ISRCTN69032034.
| S-EPMC3533804 | biostudies-literature
Project description:Infection in severe pressure ulcers can lead to sepsis with a 6-month mortality as high as 68%.Operative records of 142 consecutive operative debridements on 60 patients in a dedicated wound healing inpatient unit were reviewed, from the Wound Electronic Medical Record, for identification of key steps in debridement technique, mortality, unexpected returns, and time to discharge following debridement.The mean age of the patients was 73.1 years, and 45% were men. Most wounds (53%) were located on the hip (ischial or trochanteric); others were on the sacrum (32%) and the heels (14%). The mean initial wound area prior to debridement was 14.0 cm(2), and 83% of debridements were performed on stage IV pressure ulcers. The postoperative hospital stay averaged 4.1 days. Key steps in the technique included (1) exposure of areas of undermining by excising overlying tissue; (2) removal of callus from wound edges; (3) removal of all grossly infected tissue; and (4) obtaining a biopsy of the deep tissue after debridement of all nonviable or infected tissue for culture and pathology to determine the presence of infection, fibrosis, and granulation tissue. There was one death 9 days post-debridement of a sacral ulcer and one unplanned return to the operating room for bleeding 8 days post-debridement.Operative debridement of pressure ulcers is safe, despite the medical co-morbidities in patients with severe pressure ulcers. Proper debridement technique may prevent sepsis and death in patients with multiple co-morbid conditions.
| S-EPMC2691928 | biostudies-other
Project description:BackgroundNegative pressure wound therapy (NPWT) with instillation (NPWTi) is a new treatment for chronic skin ulcers (CSUs), but the choice of perfusate is still investigated. The clinical application of Huoxue Shengji (HXSJ) decoction has been proved to promote the formation of granulation. The formation of fresh granulation, angiogenesis, and proliferation of vascular endothelial cells are closely related. The purpose of this study was to observe the clinical efficacy of NWPT with HXSJ decoction instillation in the treatment of CSUs and to explore the potential mechanism by which HXSJ decoction promotes proliferation of vascular endothelial cells at the cellular level.MethodsIn the clinical study, the random number table was used to divide the patients into three groups (patients were numbered by visit time and assigned a random number and grouped by the remainder after the random number was divided by 3, and when the number of patients in one group reached 20, the enrolment of this group is stopped), including NPWT combined with HXSJ decoction instillation (group A), NPWT combined with normal saline instillation (group B), and NPWT (group C). Related indexes were examined, including the wound cavity volume, bacterial culture, histopathology examination, time periods of debridement, repair methods, and the time of ulcer healing. In the basic research, the effect of HXSJ decoction on the proliferation of HUVECs was analysed by CCK-8 assay and RT-PCR and western blot were used to quantify the VEGF and VEGFR-2 expression in the relevant signalling pathway.ResultsThere was no significant difference in the improvement rate of invasive cavity volume (P > 0.05) between groups A and B, but a significant difference was observed between groups A and C (P < 0.05). There was no significant difference in microbial reduction among groups (all P > 0.05). Histopathological examination showed that the microvascular count in group A was significantly higher than that in groups B and C (both P < 0.01) and there was no statistical difference between groups B and C (P > 0.05). There were no significant differences in the number of invasive lesions and repair methods among the groups (all P > 0.05). The healing time of group A was significantly faster than those of groups B and C (compared to group B, P < 0.05; compared to group C, P < 0.01), and there was no statistical difference between groups B and C (P > 0.05). In the cellular experiments, concentration screening was performed and 125 μg/mL HXSJ decoction showed the most significant effect on the proliferation of HUVECs and also enhanced the expression of VEGF and VEGFR-2.ConclusionHXSJ decoction can enhance the expression of VEGF and VEGFR-2 and promote the proliferation of HUVECs. Treatment with NWPT with HXSJ decoction instillation can further reduce the wound cavity volume; meanwhile, it can promote blood vessel formation in ulcer wounds, thus accelerating the healing of CSUs.
| S-EPMC9242787 | biostudies-literature
Project description:Saline irrigation has been shown to be both experimentally and clinically efficacious in decreasing bacterial contamination as well as decreasing infection rates. The dynamics of irrigation delivery fall into two primary categories: simultaneous and intermittent irrigation. An important component to irrigation therapy is distribution of irrigation solution to hard-to-reach areas of a wound bed, including undermining and fissure-like structures. Here we test the effectiveness of simultaneous irrigation to fill the irregular structures of a wound bed. In order to visualise the dynamic movement of irrigation solution, three-dimensional wound models were constructed using clear synthetic ballistic gel. Wounds with the aforementioned characteristics were carved into the ballistic gel with varying area, depth and volume. All three wounds were dressed as per manufacturer's instructions. Data demonstrate that simultaneous irrigation is effective in reaching all parts of a wound bed in wound models that have both undermining and tunnelling, and irrigation effectively saturates bridged wounds. Finally, this study shows that there is constant turnover of irrigation solution in the wound that is driven more by administration volume and less by flow rate. These data show that simultaneous irrigation is an effective technique for delivering irrigation solution to both simple and complex wounds.
| S-EPMC7950162 | biostudies-literature
Project description:ObjectivesThe aim of the DiaFu study was to evaluate effectiveness and safety of negative pressure wound therapy (NPWT) in patients with diabetic foot wounds in clinical practice.DesignIn this controlled clinical superiority trial with blinded outcome assessment patients were randomised in a 1:1 ratio stratified by study site and ulcer severity grade using a web-based-tool.SettingThis German national study was conducted in 40 surgical and internal medicine inpatient and outpatient facilities specialised in diabetes foot care.Participants368 patients were randomised and 345 participants were included in the modified intention-to-treat (ITT) population. Adult patients suffering from a diabetic foot ulcer at least for 4 weeks and without contraindication for NPWT were allowed to be included.InterventionsNPWT was compared with standard moist wound care (SMWC) according to local standards and guidelines.Primary and secondary outcome measuresPrimary outcome was wound closure within 16 weeks. Secondary outcomes were wound-related and treatment-related adverse events (AEs), amputations, time until optimal wound bed preparation, wound size and wound tissue composition, pain and quality of life (QoL) within 16 weeks, and recurrences and wound closure within 6 months.ResultsIn the ITT population, neither the wound closure rate (difference: n=4 (2.5% (95% CI-4.7% - 9.7%); p=0.53)) nor the time to wound closure (p=0.244) was significantly different between the treatment arms. 191 participants (NPWT 127; SMWC 64) had missing endpoint documentations, premature therapy ends or unauthorised treatment changes. 96 participants in the NPWT arm and 72 participants in the SMWC arm had at least one AE (p=0.007), but only 16 AEs were related to NPWT.ConclusionsNPWT was not superior to SMWC in diabetic foot wounds in German clinical practice. Overall, wound closure rate was low. Documentation deficits and deviations from treatment guidelines negatively impacted the outcome wound closure.Trial registration numbersNCT01480362 and DRKS00003347.
| S-EPMC7202734 | biostudies-literature
Project description: Not available
| S-EPMC8108044 | biostudies-literature