Advances in wound care最新文献

Objective: The goal of this investigation was to use comprehensive prediction modeling tools and available genetic information to try to improve upon the performance of simple clinical models in predicting whether a diabetic foot ulcer (DFU) will heal. Approach: We utilized a cohort study (n = 206) that included clinical factors, measurements of circulating endothelial precursor cells (CEPCs), and fine sequencing of the NOS1AP gene. We derived and selected relevant predictive features from this patient-level information using statistical and machine learning techniques. We then developed prognostic models using machine learning approaches and assessed predictive performance. The presentation is consistent with TRIPOD requirements. Results: Models using baseline clinical and CEPC data had an area under the receiver operating characteristic curve (AUC) of 0.73 (0.66-0.80). Models using only single nucleotide polymorphisms (SNPs) of the NOS1AP gene had an AUC of 0.67 (95% confidence interval, CI: [0.59-0.75]). However, models incorporating baseline and SNP information resulted in improved AUC (0.80, 95% CI [0.73-0.87]). Innovation: We provide a rigorous analysis demonstrating the predictive potential of genetic information in DFU healing. In this process, we present a framework for using advanced statistical and bioinformatics techniques for creating superior prognostic models and identify potentially predictive SNPs for future research. Conclusion: We have developed a new benchmark for which future predictive models can be compared against. Such models will enable wound care experts to more accurately predict whether a patient will heal and aid clinical trialists in designing studies to evaluate therapies for subjects likely or unlikely to heal.

Objective: This umbrella review aims to summarize and evaluate the evidence from current systematic reviews/meta-analyses (SRs/MAs) on the effectiveness of stem cell therapy for diabetic foot (DF). Approach: We conducted a comprehensive search in four databases for SRs/MAs that included randomized controlled trials (RCTs) on stem cell therapy for DF. Two separate researchers independently evaluated the methodological quality and evidence quality of the SRs/MAs that were included in the study. We conducted a quantitative synthesis of all RCTs included in the SRs/MAs to obtain objective and updated conclusions. Egger's test and sensitivity analysis are used to examine the reliability of the results. Results: This umbrella review includes eight SRs/MAs, and their methodological quality and evidence quality were all deemed unsatisfactory. Out of the 8 SRs/MAs, 26 RCTs were included, with a total corrected covered area of 21.4%, indicating a high degree of overlap. The test of super-significance did not yield any significant results. Our updated meta-analysis suggests that DF patients can benefit from stem cell therapy, as indicated by effectiveness in measures, including healing rate, amputation rate, ankle-brachial index, transcutaneous oxygen pressure, ulcer size reduction, complete healing time, pain-free walking distance, rest pain score, and new angiogenesis rate. Innovation: This study conducted a comprehensive evaluation and reanalysis of the current evidence regarding the effectiveness and safety of stem cell therapy for DF, which is the first of its kind. Conclusion: Based on the existing evidence, stem cell therapy is effective and safe for patients with DF.

Significance: Chronic limb threatening ischemia (CLTI) is a severe form of peripheral arterial disease (PAD) that is associated with high rates of morbidity and mortality, and especially limb loss. In patients with no options for revascularization, stem cell therapy is a promising treatment option. Recent Advances: Cell therapy directly delivered to the affected ischemic limb has been shown to be a safe, effective, and feasible therapeutic alternative for patients with severe PAD. Multiple methods for cell delivery, including local, regional, and combination approaches, have been examined in both pre-clinical studies and clinical trials. This review focuses on delivery modalities used in clinical trials that deliver cell therapy to patients with severe PAD. Critical Issues: Patients with CLTI are at high risk for complications of the disease, such as amputations, leading to a poor quality of life. Many of these patients do not have viable options for revascularization using traditional interventional or surgical methods. Clinical trials have shown therapeutic benefit for cell therapy in these patients, but methods of cell treatment are not standardized, including the method of cell delivery to the ischemic limb. Future Directions: The ideal delivery approach for stem cell therapy in PAD patients remains unclear. Further studies are needed to determine the best modality of cell delivery to maximize clinical benefits.

Significance: Half of all cancer patients receive radiation therapy as a component of their treatment regimen, and the most common resulting complication is radiation-induced fibrosis (RIF) of the skin and soft tissue. This thickening of the dermis paired with decreased vascularity results in functional limitations and esthetic concerns and poses unique challenges when considering surgical exploration or reconstruction. Existing therapeutic options for RIF of the skin are limited both in scope and efficacy. Cell-based therapies have emerged as a promising means of utilizing regenerative cell populations to improve both functional and esthetic outcomes, and even as prophylaxis for RIF. Recent Advances: As one of the leading areas of cell-based therapy research, adipose-derived stromal cells (ADSCs) demonstrate significant therapeutic potential in the treatment of RIF. The introduction of the ADSC-augmented fat graft has shown clinical utility. Recent research dedicated to characterizing specific ADSC subpopulations points toward further granularity in understanding of the mechanisms driving the well-established clinical outcomes seen with fat grafting therapy. Critical Issues: Various animal models of RIF demonstrated improved clinical outcomes following treatment with cell-based therapies, but the cellular and molecular basis underlying these effects remains poorly understood. Future Directions: Recent literature has focused on improving the efficacy of cell-based therapies, most notably through (1) augmentation of fat grafts with platelet-rich plasma and (2) the modification of expressed RNA through epitranscriptomics. For the latter, new and promising gene targets continue to be identified which have the potential to reverse the effects of fibrosis by increasing angiogenesis, decreasing inflammation, and promoting adipogenesis.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately explored. Critical Issues: This review aims to analyze the harmful impact of chemotherapy on wound healing. The analysis showed that chemotherapy drugs could inhibit cellular metabolism, cell division, and angiogenesis and lead to nerve damage. They impede the migration of cells into the wound and reduce the production of extracellular matrix. At the molecular level, they interfere with replication, transcription, translation, and cell signaling. This work reviews skin problems that patients may experience during and after chemotherapy and demonstrates insights into the cellular and molecular mechanisms of these pathologies. Future Directions: In the future, the problem of impaired wound healing in patients treated with chemotherapy may be addressed by cell therapies like autologous keratinocyte transplantation, which has already proved effective in this case. Epigenetic intervention to mitigate the side effects of chemotherapy is also worth considering, but epigenetic consequences of chemotherapy on skin cells are largely unknown and should be investigated.

Objective: Given the significant economic, health care, and personal burden of acute and chronic wounds, we investigated the dose dependent wound healing mechanisms of two Avena sativa derived compounds: avenanthramide (AVN) and β-Glucan. Approach: We utilized a splinted excisional wound model that mimics human-like wound healing and performed subcutaneous AVN and β-Glucan injections in 15-week-old C57BL/6 mice. Histologic and immunohistochemical analysis was performed on the explanted scar tissue to assess changes in collagen architecture and cellular responses. Results: AVN and β-Glucan treatment provided therapeutic benefits at a 1% dose by weight in a phosphate-buffered saline vehicle, including accelerated healing time, beneficial cellular recruitment, and improved tissue architecture of healed scars. One percent AVN treatment promoted an extracellular matrix (ECM) architecture similar to unwounded skin, with shorter, more randomly aligned collagen fibers and reduced inflammatory cell presence in the healed tissue. One percent β-Glucan treatment promoted a tissue architecture characterized by long, thick bundles of collagen with increased blood vessel density. Innovation: AVN and β-Glucan have previously shown promise in promoting wound healing, although the therapeutic efficacies and mechanisms of these bioactive compounds remain incompletely understood. Furthermore, the healed ECM architecture of these wounds has not been characterized. Conclusions: AVN and β-Glucan accelerated wound closure compared to controls through distinct mechanisms. AVN-treated scars displayed a more regenerative tissue architecture with reduced inflammatory cell recruitment, while β-Glucan demonstrated increased angiogenesis with more highly aligned tissue architecture more indicative of fibrosis. A deeper understanding of the mechanisms driving healing in these two naturally derived therapeutics will be important for translation to human use.

Objective: This study aims to analyze the potential diagnostic capability of ultrasonography (US) in detecting diabetic foot osteomyelitis (DFO) in patients with diabetic foot ulcers (DFUs). Approach: A 1-year prospective study was conducted on 47 consecutive patients with active DFUs and suspicion of DFO at a specialized diabetic foot unit. The following ultrasonographic features were evaluated at baseline: (1) periosteal reaction; (2) periosteal elevation; (3) cortical disruption; (4) sequestrum; and (5) positive power Doppler. The primary outcome measure aimed to establish the effectiveness of ultrasonographic features compared with aseptic bone culture for diagnosing DFO. Receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic performance of ultrasonographic features. Sample size could not be determined as it is the first study to assess ultrasonographic features for the diagnosis of DFO. The research adhered to the guidelines for diagnostic accuracy studies (Standards for Reporting of Diagnostic Accuracy Studies [STARD] 2015). Results: All patients (n = 24) diagnosed with DFO exhibited positive power Doppler, resulting in a sensitivity (S) and specificity (SP) of 1 and an area under the curve (AUC) of 1 (p < 0.001 [1-1]). Cortical disruption was present in 23 patients (95.8%) with DFO, yielding an S of 0.93, SP of 1, and AUC of 0.96 (p < 0.001 [0.88-1]). Innovation: It validates the diagnostic value of US for DFO as it is the first and largest study of its kind to establish a clear reference standard to guide clinician decision-making. Conclusion: This study demonstrates the effectiveness of cortical disruption and positive power Doppler in assessing DFO through US.

Objective: Autologous skin transplantation is limited by donor site availability for patients with extensive burns. The objective of this study was to demonstrate the feasibility and efficacy of split-thickness skin (STS) and dermal pixel grafts (PG) in the treatment of burns. Approach: The study was divided into three arms of validation, expansion, and combination that all followed the same study design. Sixteen deep partial-thickness burns were created on the dorsum of anesthetized pigs. Three days postinjury the burns were debrided and grafted with STS and dermal PGs. The PGs were prepared by harvesting two skin grafts (split-thickness skin graft [STSG] and dermal graft) from the same donor site going down in depth. The grafts were minced to 0.3 × 0.3 × 0.3 mm PGs and suspended in a small volume of hydrogel. Healing was monitored for 6, 10, 14, or 28 days. In the validation study the PGs at 1:2 expansion ratio were transplanted and compared with STSG and untreated controls. The expansion study investigated the maximum expansion potential of the PGs and the combination of the benefits of transplanting STS and dermal PGs together. Results: The validation study showed that when STS and dermal PGs were transplanted in a 1:2 ratio they fully re-epithelialized the wounds in 14 days. The expansion study demonstrated that using expansion ratios up to 1:500 the wounds were re-epithelialized by day 28. The combination study showed that there was no additional benefit to use STS and dermal PGs together. Innovation: Pixel grafting provides expansion ratios greater than conventional STSG. The possibility to harvest both STS and dermal PGs from the same donor area further reduces the need for healthy skin. Conclusion: STSG and dermal grafts can be minced to PGs with preserved viability and expanded up to 500 times to re-epithelialize a wound.