Dermal extracellular matrix molecules in skin development, homeostasis, wound regeneration and diseases.

The extracellular matrix (ECM) is a dynamic structure that surrounds and anchors cellular components in tissues. In addition to functioning as a structural scaffold for cellular components, ECMs also regulate diverse biological functions, including cell adhesion, proliferation, differentiation, migration, cell-cell interactions, and intracellular signaling events. Dermal fibroblasts (dFBs), the major cellular source of skin ECM, develop from a common embryonic precursor to the highly heterogeneous subpopulations during development and adulthood. Upon injury, dFBs migrate into wound granulation tissue and transdifferentiate into myofibroblasts, which play a critical role in wound contraction and dermal ECM regeneration and deposition. In this review, we describe the plasticity of dFBs during development and wound healing and how various dFB-derived ECM molecules, including collagen, proteoglycans, glycosaminoglycans, fibrillins and matricellular proteins are expressed and regulated, and in turn how these ECM molecules play a role in regulating the function of dFBs and immune cells. Finally, we describe how dysregulation of ECM matrix is associated the pathogenesis of wound healing related skin diseases, including chronic wounds and keloid.

A Multifunctional Herb-Derived Glycopeptide Hydrogel for Chronic Wound Healing.

Chronic wounds constitute an increasingly prevalent global healthcare issue, characterized by recurring bacterial infections, pronounced oxidative stress, compromised functionality of immune cells, unrelenting inflammatory reactions, and deficits in angiogenesis. In response to these multifaceted challenges, the study introduced a stimulus-responsive glycopeptide hydrogel constructed by oxidized Bletilla striata polysaccharide (OBSP), gallic acid-grafted ε-Polylysine (PLY-GA), and paeoniflorin-loaded micelles (MIC@Pae), called OBPG&MP. The hydrogel emulates the structure of glycoprotein fibers of the extracellular matrix (ECM), exhibiting exceptional injectability, self-healing, and biocompatibility. It adapts responsively to the inflammatory microenvironment of chronic wounds, sequentially releasing therapeutic agents to eradicate bacterial infection, neutralize reactive oxygen species (ROS), modulate macrophage polarization, suppress inflammation, and encourage vascular regeneration and ECM remodeling, playing a critical role across the inflammatory, proliferative, and remodeling phases of wound healing. Both in vitro and in vivo studies confirmed the efficacy of OBPG&MP hydrogel in regulating the wound microenvironment and enhancing the regeneration and remodeling of chronic wound skin tissue. This research supports the vast potential for herb-derived multifunctional hydrogels in tissue engineering and regenerative medicine.

Platelet-Derived Growth Factor Nanocapsules with Tunable Controlled Release for Chronic Wound Healing.

Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.

Development and functional testing of a novel in vitro delayed scratch closure assay.

As the development of chronic wound therapeutics continues to expand, the demand for advanced assay systems mimicking the inflammatory wound microenvironment in vivo increases. Currently, this is performed in animal models or in in vitro cell-based models such as cell culture scratch assays that more closely resemble acute wounds. Here, we describe for the first time a delayed scratch closure model that mimics some features of a chronic wound in vitro. Chronic wounds such as those suffered by later stage diabetic patients are characterised by degrees of slowness to heal caused by a combination of continued localised physical trauma and pro-inflammatory signalling at the wound. To recreate this in a cell-based assay, a defined physical scratch was created and stimulated by combinations of pro-inflammatory factors, namely interferon, the phorbol ester PMA, and lipopolysaccharide, to delay scratch closure. The concentrations of these factors were characterised for commonly used human keratinocyte (HaCaT) and dermal fibroblast (HDF) cell lines. These models were then tested for scratch closure responsiveness to a proprietary healing secretome derived from human Wharton's jelly mesenchymal stem cells (MSCs) previously validated and shown to be highly effective on closure of acute wound models both in vitro and in vivo. The chronically open scratches from HaCaT cells showed closure after exposure to the MSC secretome product. We propose this delayed scratch closure model for academic and industrial researchers studying chronic wounds looking for responsiveness to drugs or biological treatments prior to testing on explanted patient material or in vivo.

Vagus nerve stimulation: Potential for treating chronic wounds.

Vagus nerve stimulation (VNS) has been approved as a treatment for various conditions, including drug-resistant epilepsy, migraines, chronic cluster headaches and treatment-resistant depression. It is known to have anti-inflammatory, anti-nociceptive and anti-adrenergic effects, and its therapeutic potential for diverse pathologies is being investigated. VNS can be achieved through invasive (iVNS) or non-invasive (niVNS) means, targeting different branches of the vagus nerve. iVNS devices require surgical implantation and have associated risks, while niVNS devices are generally better tolerated and have a better safety profile. Studies have shown that both iVNS and niVNS can reduce inflammation and pain perception in patients with acute and chronic conditions. VNS devices, such as the VNS Therapy System and MicroTransponder Vivistim, have received Food and Drug Administration approval for specific indications. Other niVNS devices, like NEMOS and gammaCore, have shown effectiveness in managing epilepsy, pain and migraines. VNS has also demonstrated potential in autoimmune disorders, such as rheumatoid arthritis and Crohn's disease, as well as neurological disorders like epilepsy and migraines. In addition, VNS has been explored in cardiovascular disorders, including post-operative atrial fibrillation and myocardial ischemia-reperfusion injury, and has shown positive outcomes. The mechanisms behind VNS's effects include the cholinergic anti-inflammatory pathway, modulation of cytokines and activation of specialised pro-resolving mediators. The modulation of inflammation by VNS presents a promising avenue for investigating its potential to improve the healing of chronic wounds. However, more research is needed to understand the specific mechanisms and optimise the use of VNS in wound healing. Ongoing clinical trials may support the use of this modality as an adjunct to improve healing.

Advanced meta-analysis on therapeutic strategies of mesenchymal derived exosome for diabetic chronic wound healing and tissue remodeling.

BACKGROUND: Exosome (EXOs) are rapidly being identified as key mediators of cell-to-cell communication. They convey biologically active molecules to target cells, serve important roles in a range of physiological and pathological processes, and have enormous potential as novel therapeutic strategies. METHODS: Preclinical research published between 2019 and 2023 provided the study's data searched on different medline search engine, and clinicaltrials.gov was searched for clinical data. These papers were chosen because they are relevant to the research of mesenchymal stem cell-derived exosomes (MSC-EXOs). Thematic synthesis and meta-analysis were used to perform the meta-analysis of diabetic wound healing. RESULTS: For data extraction, a total of 18 preclinical and 4 clinical trials were selected. Preclinical investigations involving EXOs across various animal wound healing models showed promising potential for treatment. Specifically, following EXO treatment, there was a notable correlation with wound closure rates, with a pooled proportion of 46 % (95 % CI: 0.34; 0.59) and τ2 of 0.0593 after 3 ± 2 days, 54 % (95 % CI: 0.43; 0.65) and τ2 of 0.0465 after 7 ± 2 days, and 69 % (95 % CI: 0.62; 0.76) and τ2 of 0.0221 after 14 ± 2 days, with an egger's test p-value of <0.01. Further investigation into heterogeneity was conducted through subgroup analysis based on the source of EXO and the animal model utilized in the study. CONCLUSIONS: EXOs are proving to be viable platforms for the treatment of a wide range of disorders in clinical trials. MSC-EXOs exhibited significant diabetic wound healing capabilities across diverse outcomes including wound closure, increase angiogenesis, immunomodulatory ability and skin regeneration with its typical structure and functions.

Liver insulin-like growth factor-1 mediates effects of low-intensity vibration on wound healing in diabetic mice.

Chronic wounds in diabetic patients are associated with significant morbidity and mortality; however, few therapies are available to improve healing of diabetic wounds. Our group previously reported that low-intensity vibration (LIV) could improve angiogenesis and wound healing in diabetic mice. The purpose of this study was to begin to elucidate the mechanisms underlying LIV-enhanced healing. We first demonstrate that LIV-enhanced wound healing in db/db mice is associated with increased IGF1 protein levels in liver, blood, and wounds. The increase in insulin-like growth factor (IGF) 1 protein in wounds is associated with increased Igf1 mRNA expression both in liver and wounds, but the increase in protein levels preceded the increase in mRNA expression in wounds. Since our previous study demonstrated that liver was a primary source of IGF1 in skin wounds, we used inducible ablation of IGF1 in the liver of high-fat diet (HFD)-fed mice to determine whether liver IGF1 mediated the effects of LIV on wound healing. We demonstrate that knockdown of IGF1 in liver blunts LIV-induced improvements in wound healing in HFD-fed mice, particularly increased angiogenesis and granulation tissue formation, and inhibits the resolution of inflammation. This and our previous studies indicate that LIV may promote skin wound healing at least in part via crosstalk between the liver and wound. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Novel Sprayable Antioxidative Dressing Based on Fullerene and Curdlan for Accelerating Chronic Wound Healing.

The effective treatment of chronic wounds represents a critical global medical challenge demanding urgent attention. Persistent inflammation, driven by an excess of reactive oxygen radicals, sets in motion a detrimental cycle leading to chronic wounds and impeding the natural healing process. This study develops a sprayable wound dressing by covalently grafting amino fullerene to carboxymethylated curdlan (CMC-C). This novel dressing exhibits excellent biocompatibility, antioxidant, and reactive oxygen species scavenging properties. Furthermore, it demonstrates a targeted affinity for HEK-a cells, efficiently reducing the inflammatory response while promoting cell proliferation and migration in vitro. Moreover, the animal experiment investigations reveal that CMC-C significantly accelerates chronic wounds healing by regulating the inflammatory process, promoting collagen deposition, and improving vascularization. These results demonstrate the potential of the sprayable dressing (CMC-C) in curing the healing of chronic wounds through the modulation of the inflammatory microenvironment. Overall, the sprayable hydrogel dressing based on water-soluble derivative of fullerene and curdlan emerges as a potential approach for clinical applications in the treatment of chronic wounds.

Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.

Complication of head and neck cancer: Carotid blowout syndrome.

Carotid blowout syndrome (CBS) is an uncommon but potentially life-threatening condition characterized by the spontaneous or traumatic rupture of the carotid artery in the neck. Oftentimes, CBS is due a loss of structural arterial integrity from local radiotherapy or surgical procedures. A vast majority of patients who develop CBS also have a previous diagnosis of head and neck cancer. Due to the specific patient population who develop CBS and its life-threatening nature, CBS should be a part of emergency physicians differential for those who present with a chronic neck wound or neurological symptoms in those with a previous head and neck cancer diagnosis. In this case report, a patient with a history of squamous cell carcinoma of the oropharynx who was treated with chemoradiation therapy, presented to the emergency department with spontaneous bleeding from an existing chronic wound on the left lateral neck. Conservative measures were taken including wound dressing, and the patient was discharged to see dermatology for biopsy of a suspected cancerous lesion. Once the chronic lesion was biopsied, the patient had to be immediately rushed to the operating room due to a brisk pulsatile bleeding from puncturing the carotid artery. Proper wound packing and an ultrasound of the neck for a proper diagnosis may have prevented the need for surgical intervention in this case. Although CBS is not common, complications can lead to death as seen in this case. Timely recognition and proper interventions are critical for preventing potentially fatal outcomes in those with CBS.

Intermittent lysis on a single paper-based device to extract exosomal nucleic acid biomarkers from biological samples for downstream analysis.

As the role of exosomes in physiological and pathological processes has been properly perceived, harvesting them and their internal components is critical for subsequent applications. This study is a debut of intermittent lysis, which has been integrated into a simple and easy-to-operate procedure on a single paper-based device to extract exosomal nucleic acid biomarkers for downstream analysis. Exosomes from biological samples were captured by anti-CD63-modified papers before being intermittently lysed by high-temperature, short-time treatment with double-distilled water to release their internal components. Exosomal nucleic acids were finally adsorbed by sol-gel silica for downstream analysis. Empirical trials not only revealed that sporadically dropping 95 °C ddH2O onto the anti-CD63-modified papers every 5 min for 6 times optimized the exosomal nucleic acids extracted by the anti-CD63 paper but also verified that the whole deployed procedure is applicable for point-of-care testing (POCT) in low-resource areas and for both in vitro (culture media) and in vivo (plasma and chronic lesion) samples. Importantly, downstream analysis of exosomal miR-21 extracted by the paper-based procedure integrated with this novel technique discovered that the content of exosomal miR-21 in chronic lesions related to their stages and the levels of exosomal carcinoembryonic antigen originated from colorectal cancer cells correlated to their exosomal miR-21.

Wellbeing, quality of life and satisfaction of patients with hard-to-heal wounds: a descriptive study.

OBJECTIVE: A hard-to-heal wound is defined as a wound that failed to proceed through the normal phases of wound healing in an orderly and timely manner. The purpose of this article is to describe the impact of hard-to-heal wounds on the wellbeing, quality of life (QoL) and satisfaction with QoL of patients in Oman with hard-to-heal wounds. METHOD: A descriptive cross-sectional study of patients with hard-to-heal wounds attending three tertiary care hospitals using a self-reported questionnaire was conducted. RESULTS: A total of 275 patients took part in the study. Patients reported a low wellbeing score (67.06±19.72), moderate QoL score (52.18±25.07) and moderate satisfaction scores (68.91±23.88). Significant mean differences were reported with age, sex, educational level, monthly income and type of wound all at p<0.05. CONCLUSION: The findings of this study demonstrated that hard-to-heal wounds could influence the wellbeing, QoL and overall satisfaction with QoL of patients. DECLARATION OF INTEREST: Funding was received through an internal grant of the Sultan Qaboos University to conduct the research conducting the research (IG/CON/FACN/20/01). The authors have no conflicts of interest to declare.

Clinical use of 0.1% polyhexanide and propylbetaine on acute and hard-to-heal wounds: a literature review.

OBJECTIVE: To summarise the findings on the effect of the clinical use of 0.1% polyhexanide-propylbetaine (PHMB/betaine) solution/gel on acute and hard-to-heal (chronic) wound healing. METHOD: A literature search was conducted in MEDLINE, CINAHL, Embase, Scopus and the CENTRAL Trials Registry of the Cochrane Collaboration. Paired reviewers conducted title and abstract screening and full-text screening to identify experimental, quasi-experimental and observational studies. Study quality and risk of bias were not formally evaluated. RESULTS: A total of 17 studies met the eligibility criteria. The findings from 12 studies indicated that the use of 0.1% PHMB/betaine solution/gel had: a low risk of contact sensitivity; could help debridement during wound cleansing; aided effective wound bed preparation; reduced wound size, odour and exudate; improved pain control; reduced microbial load; and enhanced wound healing. The results of three studies indicated that both 0.1% PHMB and saline solution were effective in reducing bacterial load, while another showed that adding 0.1% PHMB to tie-over dressings had no effect on reducing bacterial loads in wounds. Another study concluded that disinfection and granulation of pressure ulcers with hydrobalance dressing with 0.3% PHMB was faster and more effective than using 0.1% PHMB/betaine. CONCLUSION: The findings of this literature review showed that 0.1% PHMB/betaine solution/gel appeared to be useful and safe for wound cleansing, was effective in removing soft debris and slough from the wound bed, and created a wound environment optimal for healing. Although these actions cannot be attributed solely to this treatment modality, these results do highlight the unique action of this combined product. However, more robust studies are needed to confirm these results.

Management of a complicated colonexposed sacrococcygeal wound after pelvic exenteration: a case report.

DECLARATION OF INTEREST: This work was supported by the Naval Medical University and the University of Shanghai for Science and Technology Joint Projects (2020-RZ04), the Innovative Clinical Research Program of Shanghai Changzheng Hospital (2020YLCYJ-Y16), and the academic project of Naval Medical University (2022QN073). The authors have no conflicts of interest to declare.

Performance of a gelling fibre dressing in management of wounds in a community setting: a sub-analysis of the VIPES study.

OBJECTIVE: To evaluate the use and performance of a gelling fibre dressing (Biatain Fiber; Coloplast A/S, Denmark) in the management of wounds in community nursing practice. METHOD: A sub-analysis of the prospective, observational, real-world VIPES (Observatoire en Ville des Plaies ExSudatives) study was conducted. Patients with exuding wounds, for which nurses chose to apply the gelling fibre as a primary dressing, were included. Outcomes included assessments of wound condition and patient/nurse opinion. RESULTS: Overall, 149 patients with acute (n=52; 34.9%) or hard-to-heal (chronic) (n=97; 65.1%) wounds were included. At baseline, mean±standard deviation wound age was 351.5±998.2 days, 108 (72.5%) wounds were moderately-to-highly exuding, and 126 (84.6%) showed exudate pooling in the wound bed. At the last follow-up visit, 29 (19.5%) wounds had healed, within a median of 36 days, and 64 (43.0%) were progressing towards healing. From baseline to the last follow-up visit, significant reductions in wound surface area (p<0.05), depth (p<0.01), exudate level (p<0.0001), and in the proportion of wounds with sloughy tissue (p<0.0001) were observed. Most wounds had no (n=86; 58.5% (two missing values)) or low exudate pooling (n=45; 30.6% (two missing values)) at the last visit and proportions of patients with healthy wound edges/periwound skin increased from baseline. At the last visit, wounds were considered improved by nurses in 71.4% (n=105) of cases, and by patients in 66.7% (n=98) of cases (two patients missing). CONCLUSION: Patients who received treatment with the gelling fibre experienced improvements in the condition of a range of complex wounds. This analysis highlights the importance of adequate exudate management, and indicates how the selection of an appropriate wound dressing can encourage healing progression. DECLARATION OF INTEREST: This study was financially supported by Laboratoires Coloplast SAS, Paris, France. Coloplast A/S funded the writing and editing of the article and contributed to its content. Coloplast A/S and Laboratoires Coloplast SAS reviewed the article for scientific accuracy. Nurses received financial compensation for their participation in the study. NA is a full-time employee of Coloplast A/S. APJ was an employee of Coloplast A/S when this article was written. FA was a full-time employee of Laboratoires Coloplast SAS at the time of publication development. RS and CJ are full-time employees of CEN Biotech. AK received an educational grant from Coloplast A/S to provide scientific input to the publication. The authors have no other conflicts of interest to declare.

Performance of a silicone foam dressing in management of wounds in a community setting: a sub-analysis of the VIPES study.

OBJECTIVE: Managing the gap between the dressing and the wound bed can facilitate the healing of exuding wounds. A silicone foam dressing (Biatain Silicone; Coloplast A/S, Denmark) was developed for application to exuding wounds. A sub-analysis of the real-world, prospective, observational VIPES (Observatoire en Ville des Plaies ExSudatives) study was conducted to investigate the use and performance of the silicone foam dressing in a community nursing setting in France. METHOD: The sub-analysis included patients from the VIPES study who received the silicone foam dressing as a primary dressing for an acute or hard-to-heal (chronic) wound. Epidemiological and wound healing outcomes were reported via a smartphone application. RESULTS: Overall, 64 patients were included in the sub-analysis. At baseline, most wounds (n=33/40; 82.5%) were in treatment failure (i.e., were stagnant, non-healing or had poor exudate management). At the last follow-up visit, a median of 22.5 (range: 3-151) days post baseline, 48.4% of wounds had healed and 25.0% were progressing towards healing. From baseline to the last follow-up visit, significant reductions in exudate level (p<0.0001) and exudate pooling (p<0.0001), and significant improvements in wound edges (p≤0.0001) and periwound skin (p<0.01) were observed. A total of 62.3% of patients had re-epithelialising wounds at the last follow-up visit. The majority of nurses (88.3%) and patients (85.0%) reported that the wound had improved and, at most dressing removals (93.5%), nurses reported that the dressing conformed closely to the wound bed. CONCLUSION: Overall, the data suggest that use of the silicone foam dressing in community practice supported the healing of wounds, illustrating the importance of exudate and gap management.

Microjet wound therapy versus sharp debridement on wound size reduction: a pilot randomised controlled trial.

OBJECTIVE: There are several methods of treating hard-to-heal (chronic) wounds, each differing in terms of efficiency, selectivity, speed, cost and pain. The objective is to activate a wound to initiate the healing cascade. For this pilot study we assessed the feasibility of a new microjet wound therapy technology compared to standard sharp debridement in wound outcomes. METHOD: A randomised, controlled, open-label pilot study was conducted in one outpatient wound clinic in Western Switzerland from March 2022 to May 2023. RESULTS: A total of 13 consecutive patients were randomly assigned to receive either microjet wound therapy (n=5) or standard mechanical debridement with instruments (n=8). As a feasibility study, there was insufficient power to detect significant differences between the groups. However, in the intervention group, our analysis may indicate a modestly faster reduction in wound area. Microjet wound therapy appears to alleviate patient anxiety and offer cost savings due to the potential for reduced time, as well as the number of required treatments. This meant fewer overall consultations. CONCLUSION: This study highlights a trend that may indicate that microjet therapy holds value in promoting faster healing of hard-to-heal wounds, and it provides a feasibility basis for a sufficiently powered multicentre trial.

Effect of oral multispecies probiotic on wound healing, periodontitis and quality of life on patients with diabetes.

OBJECTIVE: Hard-to-heal (chronic) wounds are common in patients with diabetes and are associated with a decrease in quality of life (QoL). Pathogenic bacteria often colonise hard-to-heal wounds and hinder the healing process which poses a high risk for (systemic) infections. In this study, we aim to prove that probiotics are capable of displacing human pathogenic bacteria, ameliorating inflammation and positively influencing the microenvironment/microbiome of skin and mucosa. METHOD: In this pilot study, patients with diabetes and hard-to-heal wounds with a duration of 2-120 months received an oral multispecies probiotic daily for six months. Changes in oral, stool and wound microbiome were investigated, and the effects of the probiotic intervention on wound healing, periodontitis and wound-specific quality of life (Wound-QOL-17) were analysed throughout the course of this clinical study. RESULTS: In total, seven of the 20 patients included were unable to complete the study. After six months of oral probiotic intake supplementation in five out of the remaining 13 patients, the wounds had healed completely. Most patients reported an improvement in wound-specific QoL, with particular positive effects on pain and mobility. Microbiome analysis revealed a reduction in Staphylococcus aureus and Pseudomonas aeruginosa, and Staphylococcus epidermis in healed wounds. CONCLUSION: This findings of this study provide evidence for the beneficial effects of the oral application of a multispecies probiotic over six months in patients with diabetes and hard-to-heal wounds on wound closure, wound microbial pattern, QoL, and on dental health. A randomised, placebo-controlled, double-blinded clinical trial is required to verify the results.

Pressure ulcers related to prone positioning: a pandemic amidst a pandemic.

OBJECTIVE: To explore the epidemiology and risk factors associated with the development of pressure ulcers (PUs) in patients receiving prone positioning (PP) ventilatory therapy; to compare the inflammatory status of patients who develop PUs with those who do not; and to describe the experience and useful findings that have allowed us to improve the management of these patients to reduce the incidence of PUs. METHOD: An observational, descriptive and longitudinal study was conducted, where sociodemographic and laboratory data were collected from patients who were hospitalised and required PP ventilatory therapy in critical care areas (CCA) during the months of May-October 2020. RESULTS: From the total number of patients who required PP during their CCA stay (n=240), 202 (84.2%) developed a PU. The four most frequent areas where a PU appeared were: the head and neck (n=115); the pinna (n=21); the torso (n=21); and the lower limbs (n=21). Patients who developed PU were more frequently males with higher initial levels of creatinine phosphokinase and ferritin. The incidence for each month of follow-up decreased from 8.3% to 5.8%. CONCLUSION: Regardless of the intervention, a multidisciplinary approach is required to optimise the prevention and treatment of these wounds. While PUs are often the result of other medical conditions or poor health status in general, the vast majority of PUs are avoidable.

Correlation between initial serum 25-hydroxyvitamin D and granulation growth in diabetic foot ulcers.

OBJECTIVE: To determine the correlation between initial serum 25-hydroxyvitamin D (25(OH)D) levels with granulation growth in diabetic foot ulcers (DFUs) after 21 days of treatment. METHOD: This cohort study involved patients with type 2 diabetes who had a DFU treated at hospital. Blood samples were taken from patients on admission. The chemiluminescent immunoassay technique was used to measure 25(OH)D levels. Granulation tissue growth was analysed by comparing the photographs from the initial treatment to day 21 of treatment. RESULTS: The median value of 25(OH)D levels at initial treatment was 8 ng/ml. The result showed no correlation between 25(OH)D levels and the granulation growth in DFUs (p=0.86). CONCLUSION: The initial serum 25(OH)D level was not correlated with the growth of granulation tissue in DFUs.