White adipose tissue-derived small extracellular vesicles: A new potential therapeutic reagent for accelerating diabetic wound healing.

Small extracellular vesicles (sEVs) from adipose-derived stem cells (ADSCs) have gained great attention and have been widely used in cell-free therapies for treating diabetic non-healing wounds in recent years. However, further clinical application of ADSC-sEVs have been limited due to their unsolvable defects, including cumbersome extraction procedure, high cost, low yield, etc. Thus, we urgently need to find one therapeutic reagent that could not only accelerate diabetic wound healing as ADSC-sEVs but also overcome these shortcomings. As the extraction process of adipose tissue-derived sEVs (AT-sEVs) is quite simple and labor saving, we put our focus on the efficiencies of white adipose tissue-derived sEVs (WAT-sEVs) and brown adipose tissue-derived sEVs (BAT-sEVs) in diabetic wound repair. After successfully isolating WAT-sEVs and BAT-sEVs by ultracentrifugation, we thoroughly characterized them and compared their diabetic wound healing capabilities both in vitro and in vivo. According to our study, AT-sEVs possess similar competence in diabetic wound healing as compared with ADSC-sEVs. While the effect of BAT-sEVs is not as stable as WAT-sEVs and ADSC-sEVs, the repair efficiency is also slightly lower than the other two sEVs in some cases. In summary, we are the first to discover that WAT-sEVs show great potential in diabetic wound repair. With advantages that are specific to tissue-derived sEVs (Ti-sEVs) such as time- and cost-saving, high-yield, and simple isolation procedure, we believe WAT-sEVs could serve as a novel reliable cell-free therapy for clinical diabetic wound treatment.

Closed-incision negative-pressure wound therapy after Bascom's cleft lift surgery for pilonidal sinus disease: A randomized study comparing healing.

AIM: Despite favourable outcomes in recurrence after off-midline closure techniques in pilonidal surgery, between 18% and 40% of patients suffer from prolonged postoperative wound healing. The aim of this work was to investigate if closed-incision negative-pressure wound therapy (NPWT) promotes wound healing after Bascom's cleft lift (BCL) surgery for complicated pilonidal sinus disease compared with conventional drainage and dressing. METHOD: Patients were randomized to either NPWT for 4-7 days or loop-vessel drain for 24 h and a dry dressing postoperatively. Healing was evaluated by a wound care nurse blinded for randomization at 2 and 12 weeks postoperatively (primary endpoint). Healing was defined as one or no closing defects of ≤5 mm and with no undermining. RESULTS: Although we had wanted to recruit 200 patients, the study was terminated at 118 patients (NPWT group, n = 60; control group, n = 58) after interim analysis. Patients were comparable by age, sex, body mass index, previous smoking status and indication for BCL surgery. At 2 weeks 12% of patients were healed in both the NPWT and control groups [risk difference = 0.00(95% CI -0.12 to 0.11), p = 1.00]. After 12 weeks, 68% of patients were healed in the NPWT group and 72% in the control group [risk difference = -0.03 (95% CI 0.19 to 0.13), p = 0.82]. There was no significant difference in pain experienced postsurgery. In a symptom-based questionnaire, the control group reported self-esteem to be less affected (p = 0.015). CONCLUSION: Closed-incision negative-pressure wound therapy did not significantly improve healing after BCL surgery for complicated pilonidal sinus disease.

Malignant wound aetiology, diagnosis and management: a case series and literature review.

OBJECTIVE: Malignant wounds develop when neoplastic cells invade the skin either locally or by lymphatic and haematogenous spread. They can present as hard-to-heal wounds and underlying causes include: primary skin cancer; metastasis of extracutaneous primary malignancy; malignant transformation of a hard-to-heal wound; iatrogenic injury; and cutaneous forms of cancers of non-skin origin. High clinical suspicion for a malignant wound should be confirmed with skin biopsy. The aim of this case series is to highlight a combination of both clinically clear cutaneous malignancies and not-so-obvious wounds caused by malignancy. METHOD: This case series examines patients with malignant wounds of varying aetiology and appearance. For each case, we explain the pathophysiology, atypical features, diagnostic approach and treatment. We also discuss types of wound biopsy and general wound management principles. RESULTS: Among the 11 cases analysed using descriptive statistics, median wound duration before presentation at our clinic was one year, while median age at presentation was 65 years. Our case series included the following diagnoses: cutaneous metastasis of invasive ductal carcinoma of the breast (n=2); cutaneous metastasis of colorectal adenocarcinoma (n=1); Marjolin's ulcer (n=1), basal cell carcinoma (BCC) (n=2), primary cutaneous squamous cell carcinoma (SCC) (n=1), metastatic malignant melanoma (n=1), cutaneous T-cell lymphoma (n=1), cutaneous angiosarcoma (n=1), Kaposi sarcoma (n=1) and recurrent tonsillar SCC with osteoradionecrosis (n=1); one case had both BCC and SCC. CONCLUSION: Punch and excisional biopsies were the most frequently used diagnostic techniques. Local wound therapy addressed bleeding, malodour, exudate, pain and infection. However, wound healing is usually achieved once the underlying malignancy is treated. In advanced or metastatic disease, palliative wound care aims to prevent exacerbation of existing wounds and focuses on patient comfort.

Effect of total astragalosides on diabetic non-healing wound by regulating immune microenvironment.

Aim: The aim of the research was to analyse the regulatory effect of astragaloside (AST) on the immune microenvironment of diabetic non-healing wound (DNHW), and to analyse the clinical efficacy and mechanism of wound repair in multiple layers. Material and methods: Ninety adult male Wistar rats, which were kept healthy (SPF) under natural infection, were randomly divided into three groups, namely, blank, control and observation groups, with 30 rats in each group. After adaptive feeding for 7 days, the diabetes model was established. After the model was formed, the wounds were uniformly prepared, and then the blank group only was shaved. Both the control group and the observation group were treated with moist exposure therapy. The control group was covered with physiological saline gauze, while the observation group was covered with AST gauze. The healing status of the wounds in both groups was observed and recorded on the 1st, 7th, and 14th days after formation. And the levels of α-smooth muscle actin (α-SMA) and collagen I (COL-1) in the wound tissue were measured. Results: On the 1st day after wound formation, the wound healing area, α-SMA, and COL-1 levels in the three groups were consistent (p > 0.05). On the 7th and 14th days after wound formation, the wound healing area in the three groups increased compared within the group, but only the control and observation groups had significantly higher wound healing area than on the 1st day after wound formation (p < 0.05). In addition, the blank group had lower levels of α-SMA and COL-1, while the control and observation groups had higher levels of α-SMA and COL-1 (p < 0.05). In the comparison between groups, the wound healing area, α-SMA, and COL-1 levels in the control and observation groups were higher than those in the blank group, while the wound healing area, α-SMA, and COL-1 levels in the observation group were higher than those in the control group (p < 0.05). Conclusions: AST can regulate the immune microenvironment of DNHW, improve α-SMA and COL-1, and accelerate the wound healing of DNHW.

[Plastic and reconstruction surgery for non-healing wound after posterior spinal surgery].

OBJECTIVE: To investigate the clinical significance of different plastic surgeries in the treatment of poor healing wound after posterior spinal internal fixation. METHODS: In this study, 16 patients with poor incision healing after posterior spinal internal fixation were retrospectively included, and dif-ferent plastic surgery treatment plans were determined according to the wound characteristics and defect condition. The measures included debridement, vacuum sealing drainage (VSD), and different tissue flaps according to the location and extent of the defect. RESULTS: A total of 16 patients meeting the criteria were included, of whom 3 were treated with debridement combined with VSD and wound suture directly, 6 were treated with debridement combined with Z-flap for wound repair, 1 was treated with bilateral sacrospinous muscle flap for dural defect repair combined with Z-flap for skin wound repair, 1 was treated with lectus dorsi flap for wound repair, 3 were treated with the fourth lumbar artery perforator flap for wound repair. The wound was repaired with local rotating flap in 1 case and gluteus maximus musculocutaneous flap in 1 case. Among the 16 patients, 7 cases were positive for wound culture, including 3 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa, 1 case of Staphylococcus epidermidis, 1 case of Escherichia coli, 1 case of Klebsiella pneumoniae, and the other 9 cases were negative. After surgery, there were 7 patients with different degrees of poor wound healing, including 3 patients undergoing dressing change, 2 patients undergoing secondary debridement and suture, 1 patient undergoing free scalp skin graft, and 1 patient undergoing local effusion suction treatment. All the above 7 patients were discharged from hospital after improvement, and the remaining 9 patients had good first-stage wound hea-ling after surgery. None of the 16 patients underwent internal fixation. CONCLUSION: Multiple factors could lead to poor wound healing after posterior spinal internal fixation. Early intervention, thorough debridement, removal of necrotic/infected tissue, and selection of suitable skin flap for effective wound fil-ling and covering were important means to ensure wound healing after spinal surgery and reduce removal of internal fixation.

Management of wounds with exposed bone structures using an induced-membrane followed by polymethyl methacrylate and second-stage skin grafting in the elderly with a 3-year follow-up.

The treatment of traumatic wounds with exposed bone or tendons is often challenging. An induced membrane (IM) is used to reconstruct bone defects, as it provides an effective and sufficient blood supply for bone and soft-tissue reconstruction. This study explored a novel two-stage strategy for wound management, consisting of initial wound coverage with polymethyl methacrylate (PMMA) and an autologous split-thickness skin graft under the IM. Fifty inpatients were enrolled from December 2016 to December 2019. Each patient underwent reconstruction according to a two-stage process. In the first stage, the defect area was thoroughly debrided, and the freshly treated wound was then covered using PMMA cement. After 4-6 weeks, during the second stage, the PMMA cement was removed to reveal an IM covering the exposed bone and tendon. An autologous split-thickness skin graft was then performed. Haematoxylin and eosin (H&E) staining and immunohistochemical analysis of vascular endothelial growth factor (VEGF), CD31 and CD34 were used to evaluate the IM and compare it with the normal periosteal membrane (PM). The psychological status and the Lower Extremity Function Scale (LEFS) as well as any complications were recorded at follow-up. We found that all skin grafts survived and evidenced no necrosis or infection. H&E staining revealed vascularised tissue in the IM, and immunohistochemistry showed a larger number of VEGF-, CD31- and CD34-positive cells in the IM than in the normal PM. The duration of healing in the group was 5.40 ± 1.32 months with a mean number of debridement procedures of 1.92 ± 0.60. There were two patients with reulceration in the group. The self-rating anxiety scale scores ranged from 35 to 60 (mean 48.02 ± 8.12). Postoperatively, the LEFS score was 50.10 ± 9.77. Finally, our strategy for the management of a non-healing wound in the lower extremities, consisting of an IM in combination with skin grafting, was effective, especially in cases in which bony structures were exposed in the elderly. The morbidity rate was low.

Injection of freshly collected autologous adipose tissue in complicated pilonidal disease: a prospective pilot study.

BACKGROUND: Pilonidal sinus disease (PSD) is a frequent disorder. Treatment failure and recurrence are common, leading to significant morbidity. The aim of this study was to investigate the impact and need for repeated treatment of injected autologous adipose tissue into non-healing PSD wounds and primary anal-near PSD or anal-near recurrence. METHODS: At the Department of Surgery, Randers Regional Hospital, Denmark, a prospective pilot study was conducted on consecutive PSD patients with lack of healing 3 months after surgery (Bascom's cleft lift) or with primary or recurrent anal-near pilonidal sinus disease from December 2018 to March 2020. The primary endpoint was time to healing. Autologous adipose tissue was harvested from the patients and injected into the lesions after surgical revision. Patients were examined 2 and 12 weeks after surgery. Patients with lack of healing after 12 weeks (undermining or no skin coverage) were offered re-injection. RESULTS: We included 30 patients [26 men and 4 women, median age 24 years (range 18-59 years)]. Complete healing was achieved in 25 patients [83.3%; 95% CI (69.9-96.7)]. Two patients had recurrence (6.7%). The median time to complete healing was 159 (189) days. The mean operation time was 70.6 ± 23.7 min and the mean amount of injected autologous adipose tissue was 19 ± 10 ml. There were no major complications. CONCLUSION: Freshly collected autologous adipose tissue injected into chronic non-healing or primary and recurrent PSD lesions near the anal verge is safe and efficient.

The Z-plasty contributes to the coalescence of a chronic non-healing wound.

This study aimed to explore the treatment effect of Z-plasty on a non-healing wound. A total of 72 patients diagnosed with a chronic non-healing wound in Peking University Third Hospital from November 2009 to August 2019 were retrospectively analysed. Among them, 27 patients were treated with Z-plasty, and 45 patients were treated with the general method. Detailed patient information was retrieved from medical records, including age, gender, body mass index (BMI), alcohol, smoking, and comorbidities (diabetes mellitus, hypertension, heart disease). Surgical parameters included operation time and intraoperative blood loss. Wound swelling, epidermal blisters, wound edge colour, and skin temperature at 1 day after surgery were assessed to evaluate the blood supply of the wound. Surgical complications included infection, haematoma, dehiscence, and non-healing within 2 weeks postoperatively. Student t test (for continuous data) and Chi-square test (for categorical data) were conducted to determine the statistical difference. We found no significant differences in age, gender, BMI, alcohol, smoking, and comorbidities between the two groups. Z-plasty did not show any advantages in the surgical time, invasive blood loss, hospital days, and hospitalisation expenses. The incidence of abnormal wound edge colour with Z-plasty was significantly lower than that with the general treatment (P < .05), and the Z-plasty enables better healing of the patient's wound (P < .05). Z-plasty promoted better recovery of chronic non-healing wounds than direct suturing.

Injection of freshly collected autologous adipose tissue into non-healing wounds after closed incision pilonidal surgery.

BACKGROUND: Chronic non-healing wounds are a major problem after closed incision pilonidal surgery. Freshly collected autologous adipose tissue injected into perianal fistulas in patients with Crohn's disease seems to promote healing. We investigated this technique in patients with non-healing wounds after cleft-lift surgery for pilonidal sinus disease (PSD). METHOD: In a prospective interventional pilot study conducted at our institution autologous adipose tissue from the abdominal wall was harvested, and injected into chronic non-healing PS wounds after surgical revision, healing rate being the primary outcome. The wounds were left open. Patients were followed every 2 to 3 weeks until complete healing (skin coverage, no undermining). RESULTS: 7 male patients were included (mean age 24 ± 0,6 SD years) and complete healing was achieved in 6 patients (86%). Median time to healing was 90 days (range 36-403 days ) and mean follow-up time was 388± 45 days. All patients reported major symptom relief shortly after the procedure. The mean operation time was 80 ± 23 minutes and the mean amount of freshly collected adipose tissue injected was 27.4± 12 ml. There were no complications. CONCLUSIONS: Freshly collected autologous adipose tissue injected into chronic non-healing pilonidal wounds seems safe and efficient.

Systematic review of the efficacy of topical haemoglobin therapy for wound healing.

Hypoxia is a common cause of poor wound healing, for which a variety of oxygen therapies have been developed. In order to overcome the limitations of traditional methods of treatment, namely the type of equipment, its setting, safety and cost, local haemoglobin therapy has been developed, although no reviews have so far been published. Here, we systematically review the current evidence to establish the efficacy, scope, adverse reactions, and required precautions of this new form of therapy. A search of the literature was conducted in the PubMed, Embase, Scopus, CENTRAL, CINAHL, and Web of science databases, with 17 studies meeting the eligibility criteria, comprising one animal model study and 16 clinical studies. Local haemoglobin therapy is able to safely and effectively promote the healing of a variety of wounds, especially those that are chronic and non-healing. However, premature discontinuation of this treatment can result in impediment to wound healing and even deterioration of the wound. The distinct benefit of the elimination of slough and relief of pain suggests that this technique may represent a new generation of debridement technology. Furthermore, its ease of use and convenience enables patient self-management, thereby greatly reducing health care costs.

Applying honey dressings to non-healing wounds in elderly persons receiving home care.

OBJECTIVE: The study aimed to determine the clinical effectiveness of honey dressings in the management of non-healing wounds in elderly persons receiving home care. MATERIAL AND METHODS: Design: a prospective interventional study. The sample comprised 40 Czech home care clients (aged over 65 years) with non-healing wounds who were randomly assigned to two groups. Wounds were treated with honey (intervention group) or conventional (controls) dressings. Each wound was studied for three months. A detailed description of a wound (location, size, wound bed, edges, amount of exudate, odor, adjacent skin) were recorded. Wounds were assessed with the Wound Healing Continuum and pain intensity with the Visual Analog Scale. RESULTS: Over the 3-month period, 16 (80%) individuals in the intervention group had their wounds completely healed, as compared with only six (30%) controls. There was no statistically significant difference in wound size between the groups on Day 1 (p = 0.1801). Ninety days later, the difference in wound size between the groups was statistically significant (p = 0.0041). There was a statistically significant difference in pain intensity between the two groups (p = 0.0007), with higher pain scores being indicated by controls. CONCLUSION: The study results showed that the application of honey dressings to non-healing wounds resulted in faster healing, wound size reduction and lower pain intensity.

Non-uraemic calciphylaxis successfully treated with pamidronate infusion.

Calciphylaxis is a rare and potentially fatal disease that affects the subcutaneous layer of the skin. It is a calcific vasculopathy induced by a systemic process that causes occlusion of small blood vessels. The mortality rate for individuals diagnosed with calciphylaxis is estimated between 52% and 81% with sepsis being the leading cause of death. Uraemic calciphylaxis and its known effective treatments are well documented in the literature. Unfortunately, there is no known effective treatment for non-uraemic calciphylaxis. Most of the current treatments for non-uraemic calciphylaxis are derived from uraemic calciphylaxis treatment protocols. We report a case of a 75-year-old female with calciphylaxis on the right lower extremity who was successfully treated with four pamidronate infusions in addition to local wound care. This case represents a non-uraemic calciphylaxis wound successfully treated with pamidronate infusions and standard wound care, and suggests that IV pamidronate can be an effective treatment option.

Skeletal muscle regeneration by extracellular matrix biological scaffold: a case report.

A case report of a 17-year-old female with a complex, non-healing, two-month-old wound, wherein exposed fibula was evident. On assessment, the wound measured 35cm in length, 3cm in width, and was 1cm deep, along the lateral aspect of the left lower leg. A rim of granulation tissue was visible along the wound edge. The exposed bone measured 20cm in length, and was 3cm wide. Porcine-derived, extracellular matrix (ECM) biological scaffold was placed on the wound bed to facilitate regeneration of the patient's skeletal muscle. The patient healed without incident postoperatively and was able to regain her ambulatory ability. This technique has, in the authors' experience, proved successful and without complication in complex non-healing wound cases, particularly in patients who have lost a large volume of skeletal muscle. The authors believe that patients and surgeons would benefit from early consideration of ECM biological scaffolds in similar types of large, open, and complex wounds.

The molecular biology in wound healing & non-healing wound.

The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed.

Alterations in taste perception as a result of hyperbaric oxygen therapy.

The present study evaluates the effect of hyperbaric oxygen therapy on taste sensitivity, hedonic perception of taste, and food preferences. The studied groups included 197 people in total (79 in the study group; 118 in the control group). All patients from the study group were treated with hyperbaric oxygen therapy due to chronic non-healing wounds. The control group consisted of healthy people, who did not receive hyperbaric oxygen therapy. The taste intensity, recognition thresholds, and hedonic perception were examined using gustatory tests. The aqueous solutions of sucrose for sweet, sodium chloride for salty, citric acid for sour, quinine hydrochloride for bitter, and monosodium glutamate for umami taste were used. The participants fulfilled the questionnaire to examine pleasure derived from eating certain types of dishes. Gustatory tests and analyses of the pleasure derived from eating in the study group were carried out before the first exposure to hyperbaric oxygen and then at the end of therapy, after at least 25 sessions of treatment. In the control group, examination of perception of taste sensations was conducted only once. The results of comparing patients with non-healing wounds with healthy people are characterized by reduced taste sensitivity. After participation in hyperbaric oxygen therapy, the improvement in perception of taste sensations and changes in hedonic evaluation have occurred among patients with non-healing wounds. In terms of food preference, a decreased desire for eating sweet desserts, chocolate, and crisps was observed in those patients who received hyperbaric oxygen therapy.

A Study of Arginase Expression in Chronic Non-healing Wounds.

Arginase expression has been recently shown to increase in numerous disease states like neurodegeneration, inflammation, and malignancies. Although it has been found to be functionally important in various disease pathologies, little is known about its role in wound healing. Here, we look at the expression of arginase and its isoforms in chronic non-healing wounds and also study the expression of nitric oxide synthase (NOS) and oxidative stress enzymes in them. Wound tissues and blood samples were collected at the time of index presentation and follow-up from 61 chronic non-healing wound cases. The expression patterns of arginase isoenzymes, NOS, superoxide dismutases (SOD), lactic acid dehydrogenase (LDH), and catalase were examined by using enzyme-linked immunosorbent assay, immunohistochemistry, and western blot analysis at the transcript and protein level. We reported a significant decrease of serum arginase levels in chronic nonhealing wounds in the progress of wound healing. Interestingly, tissue arginase levels were found to be increased with improved wound condition at follow-up. Tissue NOS, LDH, and catalase activity were also found to be increased with the progress of healing, whereas SOD levels were downregulated. Our findings reported increased expression at the transcript level of arginase-I and arginase-II in chronic non-healing wounds for the first time. In conclusion, we observed decreased serum arginase levels in completely healed patients as compared to non-healed cases. Our study findings support the hypothesis that inhibition of the activity of arginase delays wound healing. Arginase and iNOS may also find their place in the future as possible biomarkers for wound healing.

Nanomaterials for diabetic wound healing: Visualization and bibliometric analysis from 2011 to 2021.

Background: Nanomaterials have recently been shown to have a considerable advantage in promoting wound healing in diabetic patients or animal models. However, no bibliometric analysis has been conducted to evaluate global scientific production. Herein, this study aimed to summarize the current characteristics, explore research trends, and clarify the direction of nanomaterials and diabetic wound healing in the future. Methods: Relevant publications from 2011 to 2021 were collected from the Web of Science Core Collection on October 3, 2022. VOSviewer, CiteSpace, bibliometrix-R package, Origin 2021, and Microsoft Excel 2019 were used for bibliometric and visualization analyses. Results: We identified 409 publications relating to nanomaterials and diabetic wound healing. The number of annual productions remarkably increased from 2011 to 2021, with China and Shanghai Jiao Tong University being the most productive. The most prolific authors were Hasan Anwarul. The leading journal was the International Journal of Biological Macromolecules, with 22 publications. The most popular keywords were "nanoparticles," "delivery," "in vitro," "electrospinning," "angiogenesis," and "antibacterial." Keyword burst analysis showed "cerium oxide," "matrix metalloproteinase 9," "composite nanofiber," "hif 1 alpha," and "oxide nanoparticle" were emerging research hotspots. Conclusion: We found there has been a great progress in the application of nanomaterials in diabetic wound healing from 2011 to 2021. Although many researchers and institutions from different countries or regions contributed contributed to publications, it will be helpful or the development of this field if the degree of international cooperation can be enhanced. In the future, nanomaterials with powerful antioxidant and antibacterial qualities and promoting angiogenesis are the research hotspots.

Phosphaturic Mesenchymal Tumor Along the Hallux side Inducing a Chronic non-Healing Wound: A Case Report with Literature Review.

Phosphaturic mesenchymal tumor (PMT) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, and bone calcification disorders. Complete surgical resection of the tumor is believed to be the most effective treatment measure. However, the diagnosis of PMT is very difficult because of its insidious and small size, especially, when it appears in subcutaneous tissue with a chronic non-healing wound. We report a rare case of a 38-year-old man with a chronic non-healing wound on the left hallux for approximately eight months. Plain radiographic images and magnetic resonance imaging (MRI) revealed a cystic radiolucent shadow in the left distal phalanx. Bone scan observations also showed increased uptake in the same location. Histologically, this tumor was composed of numerous spindle cells with clusters of giant cells. The serum FGF23 level was significantly higher before surgery, with higher FGF23 levels closer to the tumor. Reverse transcription polymerase chain reaction and immunohistochemistry further confirmed the high expression of FGF23 in tumors. These data suggest that FGF23 may be a potential causative factor of PMT. The serum FGF23 levels might be useful for the diagnosis of PMT and localization of the tumor. The tumor was CD56- and D2 to 40-positive and CD31-negative. The non-healing wound caused by PMT might be attributed to the invasive growth of the tumor, destruction of intercellular junctions, and decrease in the number of endothelial cells.

Antimicrobial Effectiveness Testing of Resorbable Electrospun Fiber Matrix per United States Pharmacopeia (USP) <51>.

Contamination of surgical, traumatic, and chronic wounds with microorganisms presents a challenge to successful wound healing. In the present in vitro study, a synthetic electrospun fiber matrix (SEFM) cleared for use in the management of chronic, surgical, and traumatic wounds underwent USP (United States Pharmacopeia) <51> Antimicrobial Effectiveness Testing to determine its in vitro effectiveness against various microorganisms commonly found in non-healing wounds. The SEFM was tested in both sheet (s-SEFM) and micronized form (m-SEFM) against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus brasiliensis, Candida albicans, Proteus mirabilis, and Enterococcus faecalis. Testing was performed per the USP <51> standard on days 7, 14, and 28. Both the s-SEFM and m-SEFM met the USP <51> acceptance criteria for all microorganisms. The results obtained for s-SEFM demonstrated >1-log10 reduction against E. coli, S. aureus, P. aeruginosa, P. mirabilis, E. faecalis, and C. albicans at day 7; >3-log10 reduction with no detection of these microbes at days 14 and 28, and no increase from initial inoculum at days 7, 14, and 28 against A. brasiliensis. The results obtained for m-SEFM demonstrated >3-log10 reduction with no detectable microorganisms at day 7. The results observed in this study indicate that the SEFM is effective in vitro at inhibiting bacterial and fungal growth and colonization per USP <51> testing.

A Longitudinal Evaluation of the Bacterial Pathogens Colonizing Chronic Non-Healing Wound Sites at a United States Military Treatment Facility in the Pacific Region.

PURPOSE: The biology of chronic wounds is complex and many factors act concurrently to impede healing progress. In this study, the dynamics of microflora changes and their antibiotic susceptibility patterns were evaluated longitudinally over 30 days using data from 28 patients with a total of 47 chronic lower extremity wounds. MATERIALS AND METHODS: In this study, colonized wound isolates were characterized using cultural, biochemical, and VITEK 2 methods. Antibiotic susceptibility patterns of the wound isolates were analyzed using various phenotypic assays. Furthermore, antimicrobial resistance patterns and the presence of mutations were evaluated by a genotypic assay, whole-genome sequencing (WGS). RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa were found to be the most common strains at early time points, while members of Enterobacteriaceae were prevalent at later stages of infection. Antimicrobial resistance testing and whole-genome sequencing revealed that the molecular and phenotypic characteristics of the identified wound pathogens remained relatively stable throughout the study period. It was also noted that Enterobacter and Klebsiella species may serve as reservoirs for quinolone resistance in the Pacific region. CONCLUSION: Our observations showed that wounds were colonized with diverse bacteria and interestingly their numbers and/or types were changed over the course of infection. The rapid genetic changes that accompanied the first 4 weeks after presentation did not directly contribute to the development of antibiotic resistance. In addition, standard wound care procedures did not appear to select for resistant bacterial strains. Future efforts should focus on defining those genetic changes associated with the wound colonizing microorganisms that occur beyond 4 weeks.