Wound Bed Preparation 2024: Delphi Consensus on Foot Ulcer Management in Resource-Limited Settings.

GENERAL PURPOSE: To review a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Summarize issues related to wound assessment.2. Identify a class of drugs for the treatment of type II diabetes mellitus that has been shown to improve glycemia, nephroprotection, and cardiovascular outcomes.3. Synthesize strategies for wound management, including treatment in resource-limited settings.4. Specify the target time for edge advancement in chronic, healable wounds.

Chronic wound management in low-resource settings deserves special attention. Rural or underresourced settings (ie, those with limited basic needs/healthcare supplies and inconsistent availability of interprofessional team members) may not have the capacity to apply or duplicate best practices from urban or abundantly-resourced settings. The authors linked world expertise to develop a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. A group of 41 wound experts from 15 countries reached a consensus on wound bed preparation in resource-limited settings. Each statement of 10 key concepts (32 substatements) reached more than 88% consensus. The consensus statements and rationales can guide clinical practice and research for practitioners in low-resource settings. These concepts should prompt ongoing innovation to improve patient outcomes and healthcare system efficiency for all persons with foot ulcers, especially persons with diabetes.

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling.

Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here, we investigate the role of interneurons that continue to express NPY (NPY-INs) in the adult mouse spinal cord. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen-evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY-IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.

Management of Nonhealable and Maintenance Wounds: A Systematic Integrative Review and Referral Pathway.

GENERAL PURPOSE: To synthesize the evidence regarding nonhealable and maintenance wound management and propose an interprofessional referral pathway for wound management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES: After participating in this continuing professional development activity, the participant will apply knowledge gained to:1. Identify the ideas from the authors' systematic review that could prove useful in understanding nonhealable and maintenance wound management.2. Select evidence-based management strategies for nonhealable and maintenance wound management. ABSTRACT: OBJECTIVEThis systematic integrative review aims to identify, appraise, analyze, and synthesize evidence regarding nonhealable and maintenance wound management to guide clinical practice. An interprofessional referral pathway for wound management is proposed. DATA SOURCES: An electronic search of Scopus, Web of Science, PubMed, Academic Search Ultimate, Africa-Wide Information, Cumulative Index of Nursing and Allied Health Literature database with Full Text, Health Source: ConsumerEdition, Health Source: Nursing/Academic Edition, and MEDLINE was conducted for publications from 2011 to 2019. Search terms included (nonhealable/nonhealing, chronic, stalled, recurring, delayed healing, hard-to-heal) and wound types most associated with nonhealable or maintenance wounds. Published studies were hand searched by the authors. STUDY SELECTION: Studies were appraised using two quality appraisal tools. Thirteen reviews, six best-practice guidelines, three consensus studies, and six original nonexperimental studies were selected. DATA EXTRACTION: Data were extracted using a coding framework including treatment of underlying causes, patient-centered concerns, local wound care, alternative outcomes, health dialogue needs, challenges within resource restricted contexts, and prevention. DATA SYNTHESIS: Data were clustered by five wound types and local wound bed factors; further, commonalities were identified and reported as themes and subthemes. CONCLUSIONS: Strong evidence on the clinical management of nonhealable wounds is limited. Few studies describe outcomes specific to maintenance care. Patient-centered care, timely intervention by skilled healthcare providers, and involvement of the interprofessional team emerged as the central themes of effective management of maintenance and nonhealable wounds.

This systematic integrative review aims to identify, appraise, analyze, and synthesize evidence regarding nonhealable and maintenance wound management to guide clinical practice. An interprofessional referral pathway for wound management is proposed. An electronic search of Scopus, Web of Science, PubMed, Academic Search Ultimate, Africa-Wide Information, Cumulative Index of Nursing and Allied Health Literature database with Full Text, Health Source: Consumer Edition, Health Source: Nursing/Academic Edition, and MEDLINE was conducted for publications from 2011 to 2019. Search terms included (nonhealable/nonhealing, chronic, stalled, recurring, delayed healing, hard-to-heal) and wound types most associated with nonhealable or maintenance wounds. Published studies were hand searched by the authors. Studies were appraised using two quality appraisal tools. Thirteen reviews, six best-practice guidelines, three consensus studies, and six original nonexperimental studies were selected. Data were extracted using a coding framework including treatment of underlying causes, patient-centered concerns, local wound care, alternative outcomes, health dialogue needs, challenges within resource restricted contexts, and prevention. Data were clustered by five wound types and local wound bed factors; further, commonalities were identified and reported as themes and subthemes. Strong evidence on the clinical management of nonhealable wounds is limited. Few studies describe outcomes specific to maintenance care. Patient-centered care, timely intervention by skilled healthcare providers, and involvement of the interprofessional team emerged as the central themes of effective management of maintenance and nonhealable wounds.

C9orf72 Hexanucleotide Expansions Are Associated with Altered Endoplasmic Reticulum Calcium Homeostasis and Stress Granule Formation in Induced Pluripotent Stem Cell-Derived Neurons from Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

An expanded hexanucleotide repeat in a noncoding region of the C9orf72 gene is a major cause of amyotrophic lateral sclerosis (ALS), accounting for up to 40% of familial cases and 7% of sporadic ALS in European populations. We have generated induced pluripotent stem cells (iPSCs) from fibroblasts of patients carrying C9orf72 hexanucleotide expansions, differentiated these to functional motor and cortical neurons, and performed an extensive phenotypic characterization. In C9orf72 iPSC-derived motor neurons, decreased cell survival is correlated with dysfunction in Ca(2+) homeostasis, reduced levels of the antiapoptotic protein Bcl-2, increased endoplasmic reticulum (ER) stress, and reduced mitochondrial membrane potential. Furthermore, C9orf72 motor neurons, and also cortical neurons, show evidence of abnormal protein aggregation and stress granule formation. This study is an extensive characterization of iPSC-derived motor neurons as cellular models of ALS carrying C9orf72 hexanucleotide repeats, which describes a novel pathogenic link between C9orf72 mutations, dysregulation of calcium signaling, and altered proteostasis and provides a potential pharmacological target for the treatment of ALS and the related neurodegenerative disease frontotemporal dementia. Stem Cells 2016;34:2063-2078.

Arterial disease ulcers, part 2: treatment.

OBJECTIVES: The objectives of this article are to describe the therapeutic options available and develop an appropriate clinical approach suitable to the individual needs of the patient with arterial insufficiency, based on the wound bed preparation paradigm. This information will also assist in the integration of decision making regarding appropriate clinical intervention in an interprofessional team approach, according to the International Inter-professional Wound Caring Model 2012, with inclusion of patient-centered concerns within the patient's circle of care.

Arterial disease ulcers, part 1: clinical diagnosis and investigation.

Arterial disease (peripheral vascular disease) is the result of narrowing of the blood vessel lumen. The classic clinical signs need to be recognized early before progression to arterial predominant disease and limb ischemia. Arterial ulcers or tissue breakdown can result from trauma, infection, or other etiologies with diabetes, smoking, increasing age, and hypertension the most important risk factors. Diagnostic testing starts with a palpable pulse with special investigation including handheld Doppler for ankle brachial pressure index ratios, segmental duplex leg Doppler waveforms, and more specialized procedures, including transcutaneous oxygen saturation.

The use of a surgical incision management system on vascular surgery incisions: a pilot study.

Health care-associated infections in hospitals, including surgical site infections, contribute significantly to morbidity as well as mortality. Surgical incision management (SIM) using negative pressure wound therapy (Prevena™ Incision Management System, Kinetic Concepts, Inc., San Antonio, TX, USA) is designed to cover and protect closed surgical incisions from external factors including infectious sources and local trauma, while negative pressure removes fluid and infectious material from the surgical incision. A prospective case-control study assessed wound complications in patients undergoing vascular bypass procedures, where both femoral areas were incised to gain access to the femoral arteries. SIM was placed on one femoral area while a standard postoperative wound dressing was placed on the contralateral femoral area. Eight patients were included in this pilot study. All of them required bilateral femoral artery access. During the follow-up period patients were monitored for wound complications. All wound complications requiring surgical intervention were considered significant. No significant wound complications occurred in wounds treated with SIM, compared with three significant complications in control wounds. These preliminary data would suggest a potential reduction in wound complications and no observed increase in haemorrhage in high-risk patients with severe co-morbidities undergoing vascular surgery.

Cloxyquin (5-chloroquinolin-8-ol) is an activator of the two-pore domain potassium channel TRESK.

TRESK is a two-pore domain potassium channel. Loss of function mutations have been linked to typical migraine with aura and due to TRESK's expression pattern and role in neuronal excitability it represents a promising therapeutic target. We developed a cell based assay using baculovirus transduced U20S cells to screen for activators of TRESK. Using a thallium flux system to measure TRESK channel activity we identified Cloxyquin as a novel activator. Cloxyquin was shown to have an EC50 of 3.8 µM in the thallium assay and displayed good selectivity against other potassium channels tested. Activity was confirmed using whole cell patch electrophysiology, with Cloxyquin causing a near two fold increase in outward current. The strategy presented here will be used to screen larger compound libraries with the aim of identifying novel chemical series which may be developed into new migraine prophylactics.