Embedding Wound Hygiene into a proactive wound healing strategy.

FOREWORD. WOUND HYGIENE: THE NEXT STAGE: Since a panel published the first consensus document on Wound Hygiene in March 2020, there has been a flurry of activity in support of this newly established concept in proactive wound healing.1 The document concluded that all wounds, particularly hard-to-heal ones, will benefit from Wound Hygiene, which should be initiated at the first referral, following a full holistic assessment to identify the wound aetiology and comorbidities, and then implemented at every dressing change until full healing occurs.1 The consensus has since been bolstered by educational webinars; competency-based skills training and support; development of international Wound Hygiene ambassadors; a survey of 1478 respondents, published in July 2021;2 and a case study supplement, published in January 2022, featuring a range of wound types, anatomies and underlying conditions on the improvements in wound-healing progress that can be achieved.3 Wound Hygiene has gained its own identity and is now a term in and of itself, that encompasses a 4-step protocol of care. It is an antibiofilm approach that is increasingly being used across wound care. The results of the survey2 were particularly encouraging for seeing how far Wound Hygiene has come, and how quickly: More than half (57.4%) had heard of the concept of Wound Hygiene Of those, 75.3% have implemented Wound Hygiene Overall, following implementation of Wound Hygiene, 80.3% of respondents reported improved healing rates.2 However, the top three barriers identified by the survey-lack of confidence, competence and research data-show that there is more to be done to support Wound Hygiene in practice.2 As a result, a consensus panel of international key opinion leaders convened virtually in the summer of 2021 to discuss what has been done so far, the outputs of the survey, and ideas for addressing the unmet needs identified by the results. The result is this publication, which represents an addendum to the initial consensus document, broadening support for implementation of Wound Hygiene. This document will reflect on the reasons Wound Hygiene has been successful in its first two years of implementation, reiterating its DNA: Do not wait to treat hard-to-heal wounds Use a simple 4-step approach Enable all healthcare professionals to implement and use Wound Hygiene. The document will also discuss the evolution of the Wound Hygiene concept, focusing on how and when to implement Wound Hygiene on all tissue types of hard-to-heal wounds, and proposing what these are. The panel has expanded the framework in which Wound Hygiene is used, with the ultimate objective of introducing the concept of 'embedding Wound Hygiene intro a proactive wound healing strategy.' Key inefficiencies are often observed along the journeys of people living with hard-to-heal wounds. The limited number of specialised healthcare professionals and the resulting delays in reaching them may increase the likelihood of a hard-to-heal wound developing. In a world where so much is happening so quickly that we may, at times, feel powerless to drive change, the panel wants to provide further guidance to propel the use of Wound Hygiene. The concept of Wound Hygiene is resonating, and the panel wants you to know that in whatever region you work, in whatever area of clinical practice, you are enabled to make this change. Wielding the 4-step Wound Hygiene protocol consistently is a key action every healthcare professional in every care setting can take to tackle the global wound care crisis. Wound Hygiene has taken off-now, where do we want to land? In a place where Wound Hygiene is practised on all wounds, at every stage, until healing. The panel once again recognises that the community of global healthcare providers should consider their local standards and guidelines when applying the recommendations of this document. To this end, the panel has created a flexible 3-phase framework that situates Wound Hygiene as integral to proactive wound healing. The panel hopes you will continue to implement Wound Hygiene and see the benefits it can bring to people living with wounds, as well as those who care for them.

Implementation of Wound Hygiene in clinical practice: early use of an antibiofilm strategy promotes positive patient outcomes.

Non-healing wounds are devastating for patients, potentially causing long-term morbidity and an impaired quality of life. They also incur a huge health economic burden for health-care services. Understanding of the causes of non-healing wounds has increased significantly. While the need to address the underlying aetiology has always been acknowledged, the role of biofilm in delaying or preventing healing is now accepted. There is a consensus on the need to debride the wound to remove biofilm and then prevent its reformation, to kickstart healing. The potential benefits of incorporating an antibiofilm component within the wound bed preparation framework are clear. However, such a strategy needs to be flexible enough so that it can be implemented by all practitioners, regardless of their expertise or specialty. Wound Hygiene does this. This supplement describes the Wound Hygiene protocol, and includes a selection of case studies on different wound types, demonstrating its ease of use and effectiveness in clinical practice.

Wound hygiene survey: awareness, implementation, barriers and outcomes.

OBJECTIVE: In light of the COVID-19 pandemic, which has resulted in changes to caseload management, access to training and education, and other additional pressures, a survey was developed to understand current awareness and implementation of the wound hygiene concept into practice one year on from its dissemination. Barriers to implementation and outcomes were also surveyed. METHOD: The 26-question survey, a mixture of multiple choice and free-text, was developed by the Journal of Wound Care projects team, in consultation with ConvaTec, and distributed globally via email and online; the survey was open for just over 12 weeks. Due to the exploratory nature of the research, non-probability sampling was used. The authors reviewed the outputs of the survey to draw conclusions from the data, with the support of a medical writer. RESULTS: There were 1478 respondents who agreed to the use of their anonymised aggregated data. Nearly 90% were from the US or UK, and the majority worked in wound care specialist roles, equally distributed between community and acute care settings; 66.6% had been in wound care for more than 8 years. The respondents work across the spectrum of wound types. More than half (57.4%) had heard of the concept of wound hygiene, of whom 75.3% have implemented it; 78.7% answered that they 'always' apply wound hygiene and 20.8% 'sometimes' do so. The top three barriers to adoption were confidence (39.0%), the desire for more research (25.7%) and competence (24.8%). Overall, following implementation of wound hygiene, 80.3% reported that their patients' healing rates had improved. CONCLUSION: Respondents strongly agreed that implementing wound hygiene is a successful approach for biofilm management and a critical component for improving wound healing rates in hard-to-heal wounds. However, the barriers to its uptake and implementation demonstrate that comprehensive education and training, institutional support for policy and protocol changes, and more clinical research are needed to support wound hygiene.

Dual and Opposing Regulation of MMP1 and MMP13 by Both Arms of miR-675 in Human Articular Chondrocytes.

BACKGROUND/AIMS: MicroRNAs (miRs) are transcribed as stem-loop precursors harboring two different miRs on either side of the structure. Both miRs can modulate levels of cellular transcripts based on sequence complementarity between the miR and the mRNA target. The miR of the current study, miR-675, is encoded in the H19 gene with high expression in fetal/placental tissues but low levels in most adult tissues except for skeletal muscle and articular cartilage. miR-675 has a supportive role in expression of the major collagen component of articular cartilage (COL2A1) but it is unknown which arm contributes to this effect. Objectives: To determine the active arm of miR-675 in human articular chondrocytes. To evaluate effects of overexpression of both arms of miR-675 on MMP1 and MMP13, two enzymes involved in breakdown of COL2A1. To investigate whether abundance of both arms of miR-675 is dynamic. METHODS: miR-arm activity was determined by association with the AGO2 complex using immunoprecipitation with an AGO2 specific antibody. miR overexpression and inhibition was used to identify indirect downstream effects on two targets of the Matrix-Metalloprotease family, MMP1 and MMP13. Data was evaluated by qPCR and enzymatic activity assays. Early passage human articular chondrocytes (up to passage 2) obtained from cartilage from both healthy and osteoarthritis affected tissue were used. To evaluate miR-675 levels in a different model, myotube differentiation was employed. RESULTS: We show that both arms of miR-675 have opposing effects on MMP1 and MMP13; however only one arm, miR-675-3' is active in human articular chondrocytes. We demonstrate that during myotube differentiation, high expression of both arms of miR-675 is observed as well as an increase in expression of MMP1. CONCLUSION: We show that both arms of miR-675 result in opposing effects on two downstream molecules MMP1 and MMP13. We propose that miR abundance may arise as response to direct target transcript levels and are thus dynamic to meet the requirements of the cellular environment.

Encuesta sobre la higiene de las heridas: conocimiento, implementación, obstáculos y resultados.

OBJETIVO: Se ha desarrollado una encuesta para comprender el conocimiento y la implementación actual del concepto de higiene de las heridas un año después de su difusión. También se analizaron los obstáculos para su implementación y los resultados. MÉTODO: La revista Journal of Wound Care (JWC), con la colaboración de ConvaTec, desarrolló una encuesta de 26 preguntas, compuesta por respuestas de opción múltiple y texto libre, que distribuyó globalmente por correo electrónico y en línea; la encuesta estuvo abierta unas 12 semanas. Debido a la naturaleza exploratoria de la investigación, se utilizó una técnica de muestreo no probabilístico. Los autores analizaron los resultados de la encuesta para sacar conclusiones de los datos. RESULTADOS: Un total de 1478 participantes dio su consentimiento para el uso de sus datos combinados anonimizados. Casi el 90% era de Estados Unidos o el Reino Unido. La mayoría se desempeñaba como especialista en el cuidado de las heridas y estaba distribuido equitativamente entre centros de atención primaria y hospitales de agudos. El 66,6% había trabajado en el área de cuidado de las heridas durante más de 8 años. Los encuestados trabajaban con una amplia variedad de tipos de heridas. Más de la mitad (57,4%) había oído hablar del concepto de higiene de las heridas, y entre ellos, el 75,3% la había implementado; el 78,7% respondió que la aplicaba "siempre", mientras que el 20,8% lo hacía "a veces". Los tres principales obstáculos para su adopción fueron la confianza (39,0%), el deseo de que haya más estudios sobre la higiene de las heridas (25,7%) y la competencia (24,8%). En general, tras la implementación de la higiene de las heridas, el 80,3% informó que las tasas de cicatrización de sus pacientes habían mejorado. CONCLUSIÓN: Los encuestados estuvieron totalmente de acuerdo en que la implementación de la higiene de las heridas es un método exitoso para el tratamiento del biofilm y un componente fundamental para mejorar las tasas de cicatrización en heridas de difícil cicatrización. Sin embargo, los obstáculos para su adopción e implementación demuestran que se necesitan cursos integrales de educación y capacitación, apoyo institucional para los cambios de política, protocolos, y más estudios clínicos para promover la higiene de las heridas.

miR-1247 functions by targeting cartilage transcription factor SOX9.

microRNAs are a large and essential class of gene regulators that play key roles in development, homeostasis, and disease. They are necessary for normal skeletal development, and their expression is altered in arthritis. However, the specific role of individual microRNAs is only beginning to be unraveled. Using microRNA expression profiling in healthy human articular cartilage cells (chondrocytes), we identified miR-1247 expression as highly correlated with that of the differentiated cell phenotype. Transcribed from the DLK1-DIO3 locus, the function of miR-1247 is completely unknown. In mice its expression level was relatively high in cartilage tissue, and correlated with cartilage-associated microRNA miR-675 across a range of 15 different mouse tissues. To further probe miR-1247 function, overexpression and inhibition studies were performed in isolated human chondrocytes. Modulation of miR-1247 was found to exert profound phenotypic effects altering expression levels of cartilage master regulator transcription factor SOX9. SOX9 is essential for cartilage development and subsequent function throughout life, and mutations in this gene result in severe dwarfism. Putative miR-1247 binding sites were further investigated using luciferase reporter assays, which indicated binding of miR-1247 to a highly conserved region in the coding sequence of SOX9 but not in its 3'-UTR. Interestingly, depletion of SOX9 in human chondrocytes resulted in increased levels of the mature, processed microRNA, suggesting a negative feedback loop between miR-1247 and its target SOX9.

Computed tomographic and cross-sectional anatomy of the normal pacu (Colossoma macroponum).

The purpose of this study was to compare and define the normal cross-sectional gross and computed tomographic (CT) anatomy for a species of boney fish to better gain insight into the use of advanced diagnostic imaging for future clinical cases. The pacu (Colossoma macropomum) was used because of its widespread presence in the aquarium trade, its relatively large body size, and its importance in the research and aquaculture settings. Transverse 0.6-mm CT images of three cadaver fish were obtained and compared to corresponding frozen cross sections of the fish. Relevant anatomic structures were identified and labeled at each level; the Hounsfield unit density of major organs was established. The images presented good anatomic detail and provide a reference for future research and clinical investigation.

Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA-145 (miRNA-145).

Articular cartilage enables weight bearing and near friction-free movement in the joints. Critical to its function is the production of a specialized, mechanocompetent extracellular matrix controlled by master regulator transcription factor SOX9. Mutations in SOX9 cause campomelic dysplasia, a haploinsufficiency disorder resulting in severe skeletal defects and dwarfism. Although much is understood about how SOX9 regulates cartilage matrix synthesis and hence joint function, how this master regulator is itself regulated remains largely unknown. Here we identify a specific microRNA, miR-145, as a direct regulator of SOX9 in normal healthy human articular chondrocytes. We show that miR-145 directly represses SOX9 expression in human cells through a unique binding site in its 3'-UTR not conserved in mice. Modulation of miR-145 induced profound changes in the human chondrocyte phenotype. Specifically, increased miR-145 levels cause greatly reduced expression of critical cartilage extracellular matrix genes (COL2A1 and aggrecan) and tissue-specific microRNAs (miR-675 and miR-140) and increased levels of the hypertrophic markers RUNX2 and MMP13, characteristic of changes occurring in osteoarthritis. We propose miR-145 as an important regulator of human chondrocyte function and a new target for cartilage repair.

Parathyroid hormone-related protein is induced by hypoxia and promotes expression of the differentiated phenotype of human articular chondrocytes.

PTHrP (parathyroid hormone-related protein) is crucial for normal cartilage development and long bone growth and acts to delay chondrocyte hypertrophy and terminal differentiation in the growth plate. After growth plate closure adult HACs (human articular chondrocytes) still produce PTHrP, suggesting a possible role for this factor in the permanent articular cartilage. However, the expression regulation and function of PTHrP in the permanent articular cartilage is unknown. Human articular cartilage is an avascular tissue and functions in a hypoxic environment. The resident chondrocytes have adapted to hypoxia and use it to drive their tissue-specific functions. In the present study, we explored directly in normal articular chondrocytes isolated from a range of human donors the effect of hypoxia on PTHrP expression and whether PTHrP can regulate the expression of the permanent articular chondrocyte phenotype. We show that in HACs PTHrP is up-regulated by hypoxia in a HIF (hypoxia-inducible factor)-1α and HIF-2α-dependent manner. Using recombinant PTHrP, siRNA-mediated depletion of endogenous PTHrP and by blocking signalling through its receptor [PTHR1 (PTHrP receptor 1)], we show that hypoxia-induced PTHrP is a positive regulator of the key cartilage transcription factor SOX9 [SRY (sex determining region on the Y chromosome)-box 9], leading to increased COL2A1 (collagen type II, α1) expression. Our findings thus identify PTHrP as a potential factor for cartilage repair therapies through its ability to promote the differentiated HAC phenotype.

Ocular Surface Squamous Neoplasia: A 12-Month Prospective Evaluation of Incidence in Waikato, New Zealand.

Ocular surface squamous neoplasia (OSSN) has a high incidence in the southern hemisphere. This prospective study evaluated the incidence of OSSN in the Waikato region of New Zealand. All patients presenting with pterygium or conjunctival lesions in the Waikato region in 2020 were included. All surgeons in the region were asked to send all conjunctival and corneal specimens excised for histopathologic examination. The primary outcome measure was the incidence of OSSN. Eighty-eight percent of all excised specimens were sent for histopathologic examination. Of the 185 excised lesions sent for histopathological assessment, 18 (10%) were reported as OSSN. Patients were on average 69.4 years of age (standard deviation, SD = 6.9), predominantly male (78%), and of New Zealand-European ethnicity (89%). The OSSN annual incidence was 3.67/100,000/year. Histology grades included conjunctival intraepithelial neoplasia (CIN)-I (25%), CIN-II (25%), CIN-III (12.5%), carcinoma in situ (25%), and invasive squamous cell carcinoma (SCC) (12.5%). One patient with invasive SCC required exenteration. This study identified a high incidence rate of OSSN and is the first prospective study to analyze OSSN epidemiology in New Zealand.

Synthetic glycans control gut microbiome structure and mitigate colitis in mice.

Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. Here, we study the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures results in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including prebiotics. Model enteric pathogens grow poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increase survival, reduce weight loss, and improve clinical scores in mouse models of colitis. Synthetic glycans are thus a promising modality to improve health through selective changes to the gut microbiome.

Prototype to practice: Developing and testing a clinical decision support system for secondary stroke prevention in a veterans healthcare facility.

A clinical decision support system that guides nurse practitioners and other healthcare providers in secondary stroke prevention was developed by a multidisciplinary team with funding received from the Veterans Health Administration Office of Nursing Services. This article presents alpha-testing results obtained while using an integrated model for clinical decision support system development that emphasizes end-user perspectives throughout the development process. Before-after and descriptive methods were utilized to evaluate functionality and usability of the prototype among a sample of multidisciplinary clinicians. The predominant functionality feature of the tool is automated prompting and documentation of secondary stroke prevention guidelines in the electronic medical record. Documentation of guidelines was compared among multidisciplinary providers (N = 15) using test case scenarios and two documentation systems, standard versus the prototype. Usability was evaluated with an investigator-developed questionnaire and one open-ended question. The prototype prompted a significant increase (P < .05) in provider documentation for six of 11 guidelines as compared with baseline documentation while using the standard system. Of a possible 56 points, usability was scored high (mean, 48.9 [SD, 6.8]). These results support that guideline prompting has been successfully engineered to produce a usable and useful clinical decision support system for secondary stroke prevention.

Akt plays a critical role in replication of nonsegmented negative-stranded RNA viruses.

The order Mononegavirales (comprised of nonsegmented negative-stranded RNA viruses or NNSVs) contains many important pathogens. Parainfluenza virus 5 (PIV5), formerly known as simian virus 5, is a prototypical paramyxovirus and encodes a V protein, which has a cysteine-rich C terminus that is conserved among all paramyxoviruses. The V protein of PIV5, like that of many other paramyxoviruses, plays an important role in regulating viral RNA synthesis. In this work, we show that V interacts with Akt, a serine/threonine kinase, also known as protein kinase B. Both pharmacological inhibitors and small interfering RNA against Akt1 reduced PIV5 replication, indicating that Akt plays a critical role in PIV5 replication. Furthermore, treatment with Akt inhibitors also reduced the replication of several other paramyxoviruses, as well as vesicular stomatitis virus, the prototypical rhabdovirus, indicating that Akt may play a more universal role in NNSV replication. The phosphoproteins (P proteins) of NNSVs are essential cofactors for the viral RNA polymerase complex and require heavy phosphorylation for their activity. Inhibition of Akt activity reduced the level of P phosphorylation, suggesting that Akt is involved in regulating viral RNA synthesis. In addition, Akt1 phosphorylated a recombinant P protein of PIV5 purified from bacteria. The finding that Akt plays a critical role in replication of NNSV will lead to a better understanding of how these viruses replicate, as well as novel strategies to treat infectious diseases caused by NNSVs.

Subtenon Bupivacaine for Postoperative Pain in Patients Undergoing Pterygium Excision: A Double-Blinded Randomized Control Trial.

PURPOSE: Patients undergoing primary pterygium excision with autologous conjunctival autograft and human tissue adhesive in New Zealand, currently receive subconjunctival anesthesia with oral postoperative analgesia for pain. Our aim was to investigate the potential added benefit of intraoperative subtenon bupivacaine to this regimen. METHODS: A double-blinded, placebo-controlled, randomized trial was conducted at 2 centers. All patients received topical and subconjunctival anesthesia intraoperatively, with standardized oral analgesia as required postoperatively. Participants were allocated to receive subtenon bupivacaine 0.5% or placebo at the conclusion of surgery. Corneal epithelial defect and conjunctival graft size were recorded. Pain and ocular surface irritation were assessed (Likert scale) immediately postoperatively at 3, 6, 12, 24, and 36 hours. Cumulative oral analgesia consumption (doses) was reported at 24 and 36 hours. RESULTS: Forty-two patients were randomized with participants evenly matched at baseline. Postoperative pain at all time points ≤24 hours was significantly less (2.4 vs. 1.2; P < 0.04) in the bupivacaine arm with no difference at 36 hours (P = 0.27). Ocular surface irritation was also significantly less at all time points ≤12 hours (4.8 vs. 1.3; P < 0.01) with no difference at 24 hours (P = 0.10). Analgesia consumption was less in the bupivacaine arm at 24 (6.5 vs. 2.5; P < 0.01) and 36 hours (7.6 vs. 3.4; P < 0.01). No complications were observed. CONCLUSIONS: Intraoperative subtenon bupivacaine improves patient comfort after pterygium excision by reducing pain, irritation, and requirement for oral analgesia after surgery.

The Effect of Topical Substance-P Plus Insulin-like Growth Factor-1 (IGF-1) on Epithelial Healing After Photorefractive Keratectomy in Rabbits.

PURPOSE: To determine whether topical Substance-P (SP) plus insulin-like growth factor-1 (IGF-1) can improve corneal healing after photorefractive surface ablation in a rabbit. METHODS: After a 9.0-mm corneal de-epithelialization using a combination of chemical (18% alcohol) and mechanical debridement, excimer photorefractive surface ablation was performed bilaterally in eight rabbits (16 eyes) with an 8.0-mm ablation zone and 70-µm depth. The right eye was treated with SP (250 µg/mL) and IGF-1 (25 ng/mL) in hyaluronic acid, one drop twice a day, and the other eye treated with only hyaluronic acid. The epithelial healing process was documented photographically twice a day until healing was complete. Six rabbits were sacrificed 6 weeks after photorefractive keratectomy (PRK) and corneas examined histologically. RESULTS: Seven of eight rabbit eyes treated with SP/IGF-1 healed in a shorter time than the untreated eye. For rabbit #6, both eyes healed at the same time. The average healing time (total time until wound closure) for the treated eyes was 99 hours, while the average healing time for the untreated eyes was 170 hours (P = 0.0490). A persistent epithelial defect was found in two of the nontreated eyes but none in the treated eyes. Corneal pathology showed some degree of epithelial separation in the central corneal wound in three out of six nontreated eyes and in just the treated eye of rabbit #6. CONCLUSION: Topical SP plus IGF-1 increases the epithelial healing rate after PRK. There may have been beneficial effects upon cell adhesion as well. TRANSLATIONAL RELEVANCE: Better and faster healing.

Towards optical polarization control of laser-driven proton acceleration in foils undergoing relativistic transparency.

Control of the collective response of plasma particles to intense laser light is intrinsic to relativistic optics, the development of compact laser-driven particle and radiation sources, as well as investigations of some laboratory astrophysics phenomena. We recently demonstrated that a relativistic plasma aperture produced in an ultra-thin foil at the focus of intense laser radiation can induce diffraction, enabling polarization-based control of the collective motion of plasma electrons. Here we show that under these conditions the electron dynamics are mapped into the beam of protons accelerated via strong charge-separation-induced electrostatic fields. It is demonstrated experimentally and numerically via 3D particle-in-cell simulations that the degree of ellipticity of the laser polarization strongly influences the spatial-intensity distribution of the beam of multi-MeV protons. The influence on both sheath-accelerated and radiation pressure-accelerated protons is investigated. This approach opens up a potential new route to control laser-driven ion sources.