scholarly journals Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Lindsay Kalan ◽  
Michael Loesche ◽  
Brendan P. Hodkinson ◽  
Kristopher Heilmann ◽  
Gordon Ruthel ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
High Throughput Sequencing ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Fungal Communities ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Antibiotic Administration ◽  
Impaired Wound Healing ◽  
Over Time

ABSTRACTChronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The “mycobiome” was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylumAscomycotawere significantly greater (P= 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes.IMPORTANCEWounds are an underappreciated but serious complication for a diverse spectrum of diseases. High-risk groups, such as persons with diabetes, have a 25% lifetime risk of developing a wound that can become chronic. The majority of microbiome research related to chronic wounds is focused on bacteria, but the association of fungi with clinical outcomes remains to be elucidated. Here we describe the dynamic fungal communities in 100 diabetic patients with foot ulcers. We found that communities are unstable over time, but at the first clinical presentation, the relative proportions of different phyla predict healing times. Pathogenic fungi not identified by culture reside in necrotic wounds and are associated with a poor prognosis. In wounds stably colonized by fungi, we identified yeasts capable of forming biofilms in concert with bacteria. Our findings illuminate the associations of the fungal mycobiome with wound prognosis and healing.

Study the susceptibility pattern of bacteria isolated from infected wounds and determine various risk factors associated with foot ulcer

2020 ◽  
Vol 10 (3) ◽  
pp. 52-58
Author(s):  
Divya C Reddy ◽  
Ashin Vareeth ◽  
Bonnie Ascah Joseph ◽  
Anu Thomas ◽  
Sheba Baby John ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antimicrobial Susceptibility ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Previous History ◽  
Foot Ulcer ◽  
College Teaching ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Factors Associated

Studying of bacteria prevalence and antimicrobial susceptibility in samples from foot ulcer patients with chronic wounds will provide the epidemiological information on chronic wound infections, representing support for diagnosis, treatment and management of this pathology, thus preventing further complications of foot infection. There are many risk factors associated with a foot ulcer, so identifying those risk factors and preventing them will help in reducing the incidence of the disease to a certain extend.  Identifying the type of organisms causing the chronic wound infection, antibiotic sensitivity and resistance representing support for diagnosis, treatment and management thus preventing further complications of foot infection, and to understand the significant risk factors associated with the development of foot ulcers. An interventional study was conducted among the 80 patients with foot ulcers admitted in General surgery ward of a medical college teaching hospital from Dec 2018 to May 2019. Antimicrobial susceptibility results showed that gram-negative organism was more prevalent and among the species, the isolated majority was found to be Staphylococcus aureus 28 (0.35%) followed by Klebsiella 16(20%) and E.coli15(18.75%). The most sensitive antibiotic found was Meropenam70 (87.5%) followed by Imipenam 67(83.75%) and Linezolid 65(81.25%) The most resistant antibiotic was Cotrimoxazole 66(82.5%). This study concludes that high proportion of foot ulcers were found amongst diabetic patients than non-diabetic patients, and were often associated with trauma, cellulitis, gangrene. Some of the critical risk factors for foot ulcers included low educational status, previous history of foot ulcer, previous amputation was done, duration of ulcers, smoking, peripheral neuropathy, infection and HbA1c levels of patients.

A Retrospective Analysis of Clinical Use and Outcomes Using Viable Placental Membrane Allografts in Chronic Wounds

2021 ◽  
Vol 33 (12) ◽  
pp. 329-333
Author(s):  
Laura Swoboda
Keyword(s):  
Retrospective Analysis ◽  
Real World ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Arterial Disease ◽  
Wound Management ◽  
Foot Ulcers ◽  
Controlled Trials ◽  
Clinical Use ◽  
Exposed Bone

Introduction. Viable placental membrane (vPM) has been shown to decrease time to healing, adverse wound events, and wound-related infections. Wound research exclusion criteria commonly exclude wound types other than diabetic foot ulcers and venous leg ulcers (VLUs), comorbidities including peripheral arterial disease (PAD) and uncontrolled diabetes mellitus (DM), and wounds with exposed bone or tendon. Objective. This retrospective research study evaluated the clinical use and outcomes of the vPM with living mesenchymal stem cells used in chronic wound management in the community hospital outpatient department setting with the goal of comparing real-world use and outcomes of the product with use and outcomes described in the chronic wound literature. Materials and Methods. A retrospective analysis on vPM treatments at a Wisconsin academic health system’s community hospitals. Participants included all patients who received vPM therapy between July 1, 2016, and August 21, 2019. Results. A total of 89 patients received vPM treatment during the study period (mean age, 70 years; 69% male [n = 61], 31% female [n = 28]). Wound types were 54% diabetic or neuropathic foot ulcers (n = 48), 17% VLUs (n = 15), 7% pressure injuries (n = 6), and 22% atypical wounds (n = 20). The average wound duration prior to vPM initiation was 104 days. Average wound size at presentation was 6.9 cm2. Of study participants 54% had PAD (n = 48), 63% had DM (n = 56), 33.7% had DM and PAD (n = 30), and 17% had exposed bone or tendon (n = 15). Average adjusted time to healing after initiation of vPM was 81.2 days. The percentage of wounds healed 12 weeks after initiation of vPM treatment was 57%. Conclusions. Effectiveness of vPM observed in controlled trials also was observed in this real-world study on vPM for multiple wound types, patients with comorbidities including PAD and uncontrolled DM, and wounds with exposed bone or tendon. Results of this study were not statistically different from those reported in the literature. More randomized controlled trials are needed to explore the efficacy of vPM on patient presentations common to wound healing centers.

Recent Advances in the Development of Nitric Oxide-Releasing Biomaterials and Their Application Potentials in Chronic Wound Healing

2021 ◽  
Author(s):  
Min Wu ◽  
Zhihui Lu ◽  
Keke Wu ◽  
Changwoo Nam ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Persistent Infection ◽  
Diabetic Foot ◽  
Chronic Wounds ◽  
Pressure Ulcers ◽  
Chronic Wound ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Nitric Oxide Releasing

Chronic wounds, such as pressure ulcers, vascular ulcers and diabetic foot ulcers (DFUs), often stays in a state of pathological inflammation and suffers from persistent infection, excess inflammation, and hypoxia,...

scholarly journals Reactive oxygen species and bacterial biofilms in diabetic wound healing

2016 ◽  
Vol 48 (12) ◽  
pp. 889-896 ◽  
Author(s):  
Aksone Nouvong ◽  
Aaron M. Ambrus ◽  
Ellen R. Zhang ◽  
Lucas Hultman ◽  
Hilary A. Coller
Keyword(s):  
Reactive Oxygen Species ◽  
Wound Healing ◽  
Mouse Models ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Reactive Oxygen ◽  
Bacterial Biofilms ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Early Phases

Chronic wounds are a common and debilitating complication for the diabetic population. It is challenging to study the development of chronic wounds in human patients; by the time it is clear that a wound is chronic, the early phases of wound healing have passed and can no longer be studied. Because of this limitation, mouse models have been employed to better understand the early phases of chronic wound formation. In the past few years, a series of reports have highlighted the importance of reactive oxygen species and bacterial biofilms in the development of chronic wounds in diabetics. We review these recent findings and discuss mouse models that are being utilized to enhance our understanding of these potentially important contributors to chronic wound formation in diabetic patients.

Reducing the burden of chronic wounds: Prevention and management of the diabetic foot in the context of clinical guidelines

2008 ◽  
Vol 13 (3_suppl) ◽  
pp. 82-91 ◽  
Author(s):  
Aidan Searle ◽  
Lone Gale ◽  
Rona Campbell ◽  
Mark Wetherell ◽  
Karen Dawe ◽  
...  
Keyword(s):  
Decision Making ◽  
Shared Decision Making ◽  
Diabetic Foot ◽  
Clinical Guidelines ◽  
Chronic Wounds ◽  
Foot Ulcer ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Shared Decision ◽  
Behavioural Factors

Objectives: Chronic wounds such as diabetic foot and venous leg ulcers are a major burden for health services. Our programme was developed to explore the psychological and behavioural factors that may influence both the incidence of chronic wounds and their progression. The present article focuses on two particular aspects of the programme: patient knowledge of diabetic foot ulceration and factors influencing foot-related behaviour in patients with and without foot ulcers; and patient and podiatrist perspectives of consultations for diabetic foot ulcers. Methods: Two independent qualitative studies were undertaken: one with diabetic patients without a history of ulceration; and the other with diabetic patients with active ulceration and podiatrists treating these patients. Results: We found that patients may find it difficult understanding the rationale underlying prevention and treatment of foot ulcers; ulcerated patients may find it difficult to engage in the management of their foot ulcer outside consultations; and some podiatrists feel frustrated and unsupported in their attempts at empowering and building partnerships with patients. Conclusion: Patient and practitioner factors may contribute to the effective implementation of clinical guidelines regarding education, partnership building and shared decision-making. These findings are discussed in relation to patient education, partnership building and shared decision-making as recommended in NICE guidelines.

scholarly journals The potential of human induced pluripotent stem cells for modelling diabetic wound healing in vitro

2018 ◽  
Vol 132 (15) ◽  
pp. 1629-1643 ◽  
Author(s):  
Patricia E. Martin ◽  
Erin M. O’Shaughnessy ◽  
Catherine S. Wright ◽  
Annette Graham
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chronic Wounds ◽  
Healing Process ◽  
Diabetic Patients ◽  
Impaired Wound Healing ◽  
Induced Pluripotent

Impaired wound healing and ulceration caused by diabetes mellitus, is a significant healthcare burden, markedly impairs quality of life for patients, and is the major cause of amputation worldwide. Current experimental approaches used to investigate the complex wound healing process often involve cultures of fibroblasts and/or keratinocytes in vitro, which can be limited in terms of complexity and capacity, or utilisation of rodent models in which the mechanisms of wound repair differ substantively from that in humans. However, advances in tissue engineering, and the discovery of strategies to reprogramme adult somatic cells to pluripotency, has led to the possibility of developing models of human skin on a large scale. Generation of induced pluripotent stem cells (iPSCs) from tissues donated by diabetic patients allows the (epi)genetic background of this disease to be studied, and the ability to differentiate iPSCs to multiple cell types found within skin may facilitate the development of more complex skin models; these advances offer key opportunities for improving modelling of wound healing in diabetes, and the development of effective therapeutics for treatment of chronic wounds.

scholarly journals In Vitro Investigation of Thiol-Functionalized Cellulose Nanofibrils as a Chronic Wound Environment Modulator

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 249
Author(s):  
Anna Blasi-Romero ◽  
Carlos Palo-Nieto ◽  
Corine Sandström ◽  
Jonas Lindh ◽  
Maria Strømme ◽  
...  
Keyword(s):  
Protease Activity ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Cellulose Nanofibrils ◽  
Dermal Fibroblasts ◽  
Wound Dressings ◽  
Thiol Groups ◽  
The Stability ◽  
Over Time

There is currently a huge need for new, improved therapeutic approaches for the treatment of chronic wounds. One promising strategy is to develop wound dressings capable of modulating the chronic wound environment (e.g., by controlling the high levels of reactive oxygen species (ROS) and proteases). Here, we selected the thiol-containing amino acid cysteine to endow wood-derived cellulose nanofibrils (CNF) with bioactivity toward the modulation of ROS levels and protease activity. Cysteine was covalently incorporated into CNF and the functionalized material, herein referred as cys-CNF, was characterized in terms of chemical structure, degree of substitution, radical scavenging capacity, and inhibition of protease activity. The stability of the thiol groups was evaluated over time, and an in vitro cytotoxicity study with human dermal fibroblasts was performed to evaluate the safety profile of cys-CNF. Results showed that cys-CNF was able to efficiently control the activity of the metalloprotease collagenase and to inhibit the free radical DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), activities that were correlated with the presence of free thiol groups on the nanofibers. The stability study showed that the reactivity of the thiol groups challenged the bioactivity over time. Nevertheless, preparing the material as an aerogel and storing it in an inert atmosphere were shown to be valid approaches to increase the stability of the thiol groups in cys-CNF. No signs of toxicity were observed on the dermal fibroblasts when exposed to cys-CNF (concentration range 0.1–0.5 mg/mL). The present work highlights cys-CNF as a promising novel material for the development of bioactive wound dressings for the treatment of chronic wounds.

scholarly journals Diabetic Foot Ulcers in a Kenyan Referral and Teaching Hospital: Risk Factors, Patient Characteristics and Clinical Outcomes

2019 ◽  
Vol 1 (2) ◽  
pp. 41-51
Author(s):  
Daniel Munyambu Mutonga ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Outcomes ◽  
Diabetic Foot ◽  
Urban Areas ◽  
Hospital Admissions ◽  
Uncontrolled Hypertension ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Elevated Systolic Blood Pressure

Introduction: The burden of diabetes mellitus (DM) is increasing in resource-poor settings leading to a rise in diabetic complications. Foot complications result in almost half of all hospital admissions among diabetic patients and may result in amputations or death. Objective: To investigate the sociodemographic, clinic-laboratory characteristics and clinical outcomes of patients with diabetic foot ulcers (DFU) in a clinical setting. Materials and Methods: A cross-sectional study of 84 adult consecutive inpatients and outpatients at Kenyatta National Hospital (KNH) with any type of DM and having active DFU was conducted over 12 months. History and physical examinations findings were recorded through a structured questionnaire. Relevant data on the most recent blood tests and clinical outcomes for patients with foot ulcers were retrieved from the patients’ medical notes and analysed. Results: Majority (68%) were inpatients. The mean age was 60.30 years with 68% living in urban areas and 60% having minimal or no formal education. 8% were newly diagnosed with DM. The median duration of DM was 6.5 years. A majority (96%) had type 2 diabetes mellitus (T2DM). 45% were on insulin only, 18% on oral drugs only and 32% on a combination of both. The median random blood sugar was 9.60 mmol/L and glycated haemoglobin was 8.80%. Although 61% of patients had co-morbid hypertension, only about 40% had elevated systolic blood pressure (BP) while 23% had elevated diastolic pressures. A majority of the patients had good lipid profile, 85% with desirable total cholesterol and 70% having ideal low-density lipoproteins. The mortality rate among patients with DFU was 11%. Conclusion: There are poor outcomes for patients with DFU in this setting such as poor wound healing, high recurrence rates, increased amputations and mortality compared to previous studies. However, the prevalence of uncontrolled hypertension, dyslipidaemia and neuropathy was much lower than earlier local reports.

Potential Biomolecules and Current Treatment Technologies for Diabetic Foot Ulcer: An Overview

2018 ◽  
Vol 15 (1) ◽  
pp. 2-14 ◽  
Author(s):  
Zenith Khashim ◽  
Shila Samuel ◽  
Nallusamy Duraisamy ◽  
Kathiravan Krishnan
Keyword(s):  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Limb Amputation ◽  
Foot Ulcers ◽  
Diabetic Patients ◽  
Diabetic Foot Ulcers ◽  
Impaired Wound Healing ◽  
Advanced Therapies ◽  
Dressing Materials

Background:Diabetic foot ulceration remains a major challenge and is one of the most expensive and leading causes of major and minor amputations among patients with diabetic foot ulcer. Hence the purpose of this review is to emphasize on potential molecular markers involved in diabetic foot ulcer physiology, the efficacy of different types of dressing materials, adjunct therapy and newer therapeutic approach like nanoparticles for the treatment of diabetic foot ulcer.Methods:We conducted a systematic literature review search by using Pubmed and other web searches. The quality evidence of diabetic foot ulcer biomolecules and treatments was collected, summarized and compared with other studies.Results:The present investigation suggested that impaired wound healing in diabetic patients is an influence of several factors. All the advanced therapies and foot ulcer dressing materials are not suitable for all types of diabetic foot ulcers, however more prospective follow ups and in vivo and in vitro studies are needed to draw certain conclusion. Several critical wound biomolecules have been identified and are in need to be investigated in diabetic foot ulcers. The application of biocompatible nanoparticles holds a promising approach for designing dressing materials for the treatment of diabetic foot ulcer.Conclusion:Understanding the cellular and molecular events and identifying the appropriate treatment strategies for different foot ulcer grades will reduce recurrence of foot ulcer and lower limb amputation.

scholarly journals Vaccarin Regulates Diabetic Chronic Wound Healing through FOXP2/AGGF1 Pathways

2020 ◽  
Vol 21 (6) ◽  
pp. 1966
Author(s):  
Yixiao Liu ◽  
Jiangnan Sun ◽  
Xinyu Ma ◽  
Shuangshuang Li ◽  
Min Ai ◽  
...  
Keyword(s):  
Wound Healing ◽  
High Glucose ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Angiogenic Factor ◽  
Cell Counting ◽  
Sensory Loss ◽  
Diabetic Patients ◽  
And Migration ◽  
Proliferation And Migration

Background: Diabetes mellitus is a growing global health issue nearly across the world. Diabetic patients who are prone to develop diabetes-related complications often exhibit progressive neuropathy (painless and sensory loss). It is usual for small wounds to progress to ulceration, which especially worsens with peripheral arterial disease and in the presence of anaerobic bacteria, culminating into gangrene. In our study, vaccarin (VAC), the main active monomer extracted from Chinese herb vaccariae semen, is proven to have a role in promoting diabetic chronic wound healing through a cytoprotective role under high glucose conditions. Materials and methods: We constructed a pressure ulcer on both VAC-treated and control mice based on a type 1 diabetes (T1DM) model. The wound healing index was evaluated by an experimental wound assessment tool (EWAT). We also determined the effect of VAC on the proliferation and cell migration of human microvascular endothelial cells (HMEC-1) by a cell counting kit (CCK-8), a scratch and transwell assay. Results: The results demonstrated that VAC could promote the proliferation and migration of high glucose-stimulated HMEC-1 cells, which depend on the activation of FOXP2/AGGF1. Activation of the angiogenic factor with G patch and FHA domains 1 (AGGF1) caused enhanced phosphorylation of serine/threonine kinase (Akt) and extracellular regulated protein kinases (Erk1/2). By silencing the expression of forkhead box p2 (FOXP2) protein by siRNA, both mRNA and protein expression of AGGF1 were downregulated, leading to a decreased proliferation and migration of HMEC-1 cells. In addition, a diabetic chronic wound model in vivo unveiled that VAC had a positive effect on chronic wound healing, which involved the activation of the above-mentioned pathways. Conclusions: In summary, our study found that VAC promoted chronic wound healing in T1DM mice by activating the FOXP2/AGGF1 pathway, indicating that VAC may be a promising candidate for the treatment of the chronic wounds of diabetic patients.

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