Alisha R. Oropallo 1,*, Thomas E. Serena 2, David G. Armstrong 3 and Mark Q. Niederauer 4
1 Comprehensive Wound Healing Center and Hyperbarics, Department of Vascular Surgery, Zucker School of Medicine Hofstra/Northwell, Hempstead, NY 11549, USA
2 Serena Group Research Foundation, Cambridge, MA 02140, USA; serena@serenagroups.com
3 Limb Preservation Program, Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA; armstrong@usa.net
4 EO2 Concepts, San Antonio, TX 78249, USA; m.niederauer@eo2.com
* Correspondence: aoropallo@northwell.edu; Tel.: +1-516-233-3780

Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) including continuous diffuse oxygen therapy (CDOT) are often utilized to enhance wound healing in patients with diabetic foot ulcerations. High pressure pure oxygen assists in the oxygenation of hypoxic wounds to increase perfusion. Although oxygen therapy provides wound healing benefits to some patients with diabetic foot ulcers, it is currently performed from clinical examination and imaging. Data suggest that oxygen therapy promotes wound healing via angiogenesis, the creation of new blood vessels. Molecular biomarkers relating to tissue inflammation, repair, and healing have been identified. Predictive biomarkers can be used to identify patients who will most likely benefit from this specialized treatment. In diabetic foot ulcerations, specifically, certain biomarkers have been linked to factors involving angiogenesis and inflammation, two crucial aspects of wound healing. In this review, the mechanism of how oxygen works in wound healing on a physiological basis, such as cell metabolism and growth factor signaling transduction is detailed. Additionally, observable clinical … read more

Diabetic foot ulcers debridement should be part of the standard of care, and repetitive weekly debridement may be beneficial … Written by Kristin Della Volpe … Frequent debridement of chronic wounds is associated with improved healing, according to James Wilcox, RN, lead author of a retrospective study of more than 300,000 wounds. Diabetic foot ulcers accounted for a large percentage of these wounds … “An effective healing strategy for chronic wounds should include an early and accurate diagnosis of wound etiology, as well as the appropriate application of debridement and advanced healing modalities in an effort to achieve optimal outcomes,” said Mr. Wilcox, who is Director of Research and Quality for Medical Affairs at Healogics in Jacksonville, FL, and Immediate Past President of the Baromedical Nurses Association … read more

Patients with diabetes have a higher risk of ulceration, typically on the lower extremities. Other factors contributing to the risk of foot ulceration include peripheral neuropathy, peripheral arterial disease, infection and pressure.

Symptoms of Diabetic Foots Ulcers

Neuropathy, a major contributing factor in the development of diabetic foot ulcers, may present as a stinging, burning or shooting pain in the lower extremities that over time may progress to a loss of sensation in the feet or may initially develop as a progressive loss of sensation. This loss of feeling can cause patients with diabetes to further injure their feet and legs, opening them to infection and thus, ulceration.

read more

Cure For Diabetic Foot Ulcers: People with diabetes, often struggle with diabetic foot ulcers, but not anymore. A team of scientists from the Banaras Hindu University (BHU) have found a cure. The findings of the study were published in the National Centre for Biotechnology Information, National Institutes of Health, US. The team led by Prof Gopal Nath of the department of Microbiology, Institute of Medical Sciences, said that wounds that took months and years to heal, could now be cured in days or months … read more

Adults with diabetic foot ulcers and peripheral artery disease who receive revascularization surgery are at no greater risk for amputation or death following endovascular surgery compared with open vascular surgery, according to findings published in the Journal of Diabetes and its Complications … “The present large cohort study showed in a propensity score-adjusted analysis that there was no difference in amputation-free survival in patients with diabetic foot ulcers and peripheral arterial disease regardless of whether endovascular or open vascular surgery was chosen as first-line vascular intervention,” Talha Butt, MD, of the department of cardiothoracic and vascular surgery at Skåne University Hospital in Sweden … read more

Diabetic foot ulcers can take up to 150 days to heal. A biomedical engineering team wants to reduce it to 21 days … They’re planning to drop the healing time by amplifying what the body already does naturally: build layers of new tissue pumped up by nitric oxide. In patients with diabetes, impaired nitric oxide production lessens the healing power of skin cells and the Centers for Disease Control reports that 15 percent of Americans living with type II diabetes struggle with hard-to-heal foot ulcers. However, simply pumping up nitric oxide is not necessarily better. The long-term plan of Michigan Technological University …. read more

A new system that uses a multilayer patch made with a patient’s own leukocytes, platelets, and fibrin can speed the healing of diabetic foot ulcers, according to new findings … “The use of LeucoPatch is associated with significant enhancement of healing of hard-to-heal foot ulcers in people with diabetes,” Dr. Frances Game of Derby Teaching Hospitals NHS Foundation Trust in the UK and colleagues conclude in The Lancet Diabetes & Endocrinology online September 19 report … read more

medwireNews: A low-cost, smartphone-based infrared (IR) camera works as well as a high-end IR camera for the detection of diabetic foot ulcers (DFU), study findings indicate … “An advanced home assessment tool to monitor the foot in people with diabetes is desirable, and for this measurement of foot skin temperature is a promising modality,” Rob van Doremalen (University of Twente, Enschede, the Netherlands) and co-authors explain … They acquired plantar images of both feet from 32 participants (mean age 67 years, 75% men) with a current (n=28) or recently healed (n=4) DFU using the FLIR-One IR camera (FLIR Systems, Wilsonville, Oregon, USA) attached to a Motorola XT1642 Moto G4 Plus smartphone (Motorola Mobility LLC, Chicago, Illinois, USA) … read more

The first patient has been dosed in a Phase III trial assessing ViroMed’s VM202, the first pivotal study of a gene therapy indicated for patients with nonhealing diabetic foot ulcers (NHU) and concomitant peripheral artery disease (PAD).

The Phase III trial (NCT02563522) is a double-blind, placebo-controlled, multicenter study designed to evaluate VM202 for safety and efficacy in 300 adults with a diabetic foot ulcer and concomitant PAD. Two hundred patients will be randomized to VM202 and the other 100 to placebo, ViroMed’s U.S. division VM BioPharma said yesterday. … read more

The Alliance submitted detailed comments and recommendations to Novitas on its Draft LCD on Skin Substitutes for the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers (DL35041) and accompanying draft Local Coverage Article (DA54117). In April oral comments submitted at Novitas’ public meeting, the Alliance had flagged – among other issues – provisions in the policy not supported by scientific evidence, as well as conficting and/or clinically incorrect policy language. In written comments, the Alliance submitted a chart (attachment A) detailing the specific provisions/policy language it flagged as problematic, the issues of concern underlying to those provisions, specific language changes to address the concern, and the clinical evidence supporting these recommendations. The chart was accompanied by additional attachments, including HCPCS and ICD-10 Codes to be added and a red-lined mark-up of suggested line edits (attachments B-E). See comments and attachments below … read more

• Diabetic foot ulcers (DFU) are chronic wounds in the foot or feet associated with neuropathy and/or peripheral artery disease (PAD) of the lower limb in patients with diabetes mellitus.
• Reports from the Centers for Disease Control and Prevention show that in the United States there are nearly one in four adults living with diabetes, which indicates that a large number of Americans are at risk of DFU.
• DFUs will develop in up to 34% of patients with diabetes at some time in their lives, and of those, approximately 15%–25% will require an amputation.
• Moderate or severe malnutrition has been identified in over half of patients with DFU, and malnutrition in DFU is correlated with increased lower-extremity amputation.

… read more

Diabetic foot ulcers (DFU) are chronic wounds in the foot or feet associated with neuropathy and/or peripheral artery disease (PAD) of the lower limb in patients with diabetes mellitus. Reports from the Centers for Disease Control and Prevention show that in the United States there are nearly one in four adults living with diabetes, which indicates that a large number of Americans are at risk of DFU. DFUs will develop in up to 34% of patients with diabetes at some time in in their lives, and of those, approximately 15%–25% will require an amputation. Moderate or severe malnutrition has been identified in over half of patients with DFU, and malnutrition in DFU is correlated with increased lower-extremity amputation. Improvements in wound care therapy, including nutrition interventions, can reduce the financial burden of DFUs and increase life expectancy and quality of life … read more

• Diabetic foot ulcers (DFU) are chronic wounds in the foot or feet associated with neuropathy and/or peripheral artery disease (PAD) of the lower limb in patients with diabetes mellitus.
• Reports from the Centers for Disease Control and Prevention show that in the United States there are nearly one in four adults living with diabetes, which indicates that a large number of Americans are at risk of DFU.
• DFUs will develop in up to 34% of patients with diabetes at some time in in their lives, and of those, approximately 15%–25% will require an amputation.
• Moderate or severe malnutrition has been identified in over half of patients with DFU, and malnutrition in DFU is correlated with increased lower-extremity amputation.
• Improvements in wound care therapy, including nutrition interventions, can reduce the financial burden of DFUs and increase life expectancy and quality of life.

… read more

Diabetic foot ulcers (DFUs) are rising in prevalence globally, and particularly in the Gulf region. Infection remains a common and serious complication in managing DFUs. A need was identified for local guidelines that considered cultural and religious practices in the Gulf region, as well as clinical issues. This consensus document aims to provide practitioners with guidance on identifying and managing DFUs, which can be directly applied to local practice … download (pdf)

Local injection of mesenchymal stem cells derived from autologous bone marrow shows promise in healing recalcitrant neuropathic diabetic foot ulcers, a novel study from Egypt shows … Presenting the results at the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting, Ahmed Albehairy, MD, from Mansoura University, Egypt, said: “In patients who received the mesenchymal stem cells, ulcer reduction was found to be significantly higher compared with patients on conventional treatment after both 6 weeks and 12 weeks of follow-up. This is despite the fact that initial ulcer size was larger in the stem-cell–treated group.” … read more

StimLabs, a provider of regenerative technologies and products, has enrolled first patient in its trial designed to assess the safety and efficacy of Revita human placental graft in diabetic foot ulcers (DFUs) … Revita is said to be the first amniotic placental membrane allograft to capture the complete intact membrane in a shelf-stable format … The multi-center randomized, comparative and controlled trial will assess the efficacy of Revita full thickness placental allograft in improving wound closure rates and mean closure time in DFUs compared against current standards of wound care treatment … StimLabs is carrying out the trial at primary institutions/centers in the US. The trial includes patients who suffer from type 1 or 2 diabetes … read more

Well September has passed but this is a wealth of information on DFUs from WoundSource:

As part of the WoundSource Practice Accelerator series, we present the following education on a variety of topics related to the assessment, management and prevention of diabetic foot ulcers.

Comprehensive treatment of diabetic foot ulcers (DFUs) includes moist local or topical wound care, serial sharp debridement, treatment of infection, mechanical offloading, glycemic control, nutritional management, and overall chronic disease management. These facets of therapy are best addressed by an interdisciplinary approach.

If we understand the principles of healing, what can we do to prevent the pathologic process of DFUs? Instituting measures to prevent development of DFUs can decrease morbidity and mortality. There are several organizations with guidelines for prevention of DFU and subsequent complications including amputation, infection, and loss of independence. This article will review the highlights of some of the most recent guidelines for DFU prevention … read more

MiMedx Group (NASDAQ:MDXG) is up 6% premarket on light volume on the heels of the publication of a study evaluating its dehydrated human umbilical cord (dHUC) for the treatment of chronic diabetic foot ulcers in the International Wound Journal … In the intent-to-treat group, 70% of patients receiving weekly dHUC allograft achieved complete healing by week 12 compared to 48% of those receiving standard-of-care (SOC) treatment for 12 weeks (p=0.0089) … read more

MUNICH — Local injection of mesenchymal stem cells derived from autologous bone marrow shows promise in healing recalcitrant neuropathic diabetic foot ulcers, a novel study from Egypt shows.

Presenting the results at the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting, Ahmed Albehairy, MD, from Mansoura University, Egypt, said: “In patients who received the mesenchymal stem cells, ulcer reduction was found to be significantly higher compared with patients on conventional treatment after both 6 weeks and 12 weeks of follow-up. This is despite the fact that initial ulcer size was larger in the stem-cell–treated group.”

After 6 weeks, median ulcer reductions were 49.9% and 7.67% (P = .001) in stem-cell–treated and control groups, respectively, and after 12 weeks, median ulcer reductions were 68.24% and 5.27% (P = .0001). Complete healing was achieved in one case in the mesenchymal stem cell–treated group.

“The healing mechanism may be due to the pure effect of injected mesenchymal stem cells … read more

Diabetic foot ulcers (DFUs) are arguably among the most difficult types of wounds to manage; the etiology of these wounds poses some of the greatest clinical challenges for healing, considering the multifaceted nature of diabetes mellitus (DM). Multiple patient-related factors must be addressed and controlled through faithful adherence to the prescribed plan of care, which is developed by both the patient and clinicians to ensure success … Treatment of DFUs requires multidisciplinary provider involvement (podiatry, vascular, infectious disease, internal medicine or family practice, endocrinology, cardiology, nephrology, and physical therapy). The standard of care for patients with DFUs includes medical management of chronic disease, including nutrition and glucose control, routine wound assessments with ulcer grading and risk stratification, topical wound management with attention to serial debridements and moist wound healing … read more

A new formulation developed by University of South Australia scientists to treat antimicrobial-resistant bacterial infections in diabetic foot ulcers could also be used to kill the COVID-19 virus circulating in air conditioning systems … Enhancing cold plasma ionized gas with peracetic acid eradicates bacteria in wounds and substantially reduces SARS-CoV-2 viral loads, Australian and UK scientists claim in a paper published in Applied Physics Letters … read more

 
The WHS Communications Committee is pleased to launch the WRR Fireside Chat video series to feature groundbreaking research in Wound Repair and Regeneration (WRR).

Each video Drs. Mitch Sanders, PhD and Kyle Quinn, PhD will feature a recent article in WRR.

Impact of repeated remote ischemic conditioning on diabetic foot ulcers: A proof-of-concept study
Author: Matthew Regulski, DPM

 View Article

in Appreciably Shorter Time and at Lower Costs

Demonstrates Superiority Compared to Standard of Care in Prospective, Randomized Controlled Trial
PRINCETON, N.J.–(BUSINESS WIRE)–The Geistlich Medical business unit of Geistlich Pharma AG, a family owned, Swiss-based global leader in regenerative solutions, is proud to announce the results from their clinical study of the Geistlich Derma-Gide® Advanced Wound Matrix. The study, “Use of a Purified Reconstituted Bilayer Matrix (PRBM) in the Management of Chronic Diabetic Foot Ulcers Improves Patient Outcomes vs Standard of Care – Results of a Prospective Randomized Controlled Multi-Center Clinical Trial,” was peer-reviewed and published in the International Wound Journal – Wiley Online Library … The paper was authored by David G. Armstrong, DPM, MD, PhD; Dennis P. Orgill, MD, PhD; Robert D. Galiano, MD; Paul M. Glat, MD; Jarrod P. Kaufman, MD; Marissa J. Carter, MA, PhD; Lawrence A. DiDomenico, DPM; and Charles M. Zelen, DPM, FACFAS. The paper is now available in the Wiley Online Library at https://onlinelibrary.wiley.com/doi/full/10.1111/iwj.13715 … In a 40-patient, prospective, randomized, controlled multicenter clinical trial comparing a purified reconstituted bilayer matrix (PRBM, Geistlich Derma-Gide) vs. Standard of Care (SOC – collagen alginate dressing), Geistlich Derma-Gide was found to be superior relative to healing rates and time to wound closure … read more

A Randomized Controlled Trial in Comparison With Conventional Methods
Diabetic foot ulcers (DFUs) are a global burden on health care systems. Despite the availability of various treatment modalities, many DFUs do not heal. Nonhealing wounds can lead to various complications, which add to significant morbidity in terms of the degree of moisture retained in the dressing, pain, foul order, and restriction of daily activities. A different treatment modality that can promote the wound healing process earlier (and is cost-effective, easy to use, and readily available) may be necessary to consider. Objective. The purpose of the current study was to demonstrate the efficacy of ultrathin skin grafting (UTSG) in the early healing of DFUs in terms of cost-effectiveness, reduced total number of hospital visits, and final wound outcome (ie, limb salvage rate). Materials and Methods. A randomized controlled trial was conducted in which 52 patients were treated with either UTSG … read more

Future applications for the early, preventative use of amniotic membrane allografts in addition to the current standard of care for DFUs present a novel opportunity to reduce long-term morbidity and amputation risk in diabetic patients.

PENSACOLA, Fla., Aug. 8, 2022 /PRNewswire/ — A new MDPI study, co-authored by Regenative Labs signifies a huge win for patients suffering from diabetic foot ulcers (DFUs). DFUs are debilitating for an individual. They are painful, long lasting, and, even with proper care, can lead to amputation. The current standard of care for DFUs is debridement, the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue. The increased healing time and augmented risk of amputation associated with the current standard of care only solidifies the need for new DFU treatment alternatives. Regenerative medicine is such an alternative.

With approximately 37.3 million diabetic adults in the United States, physicians are faced with an epidemic. Given the projected increase of 1.4 million new diagnoses of diabetes mellitus each year, advancing knowledge and care for the disease and its related conditions is especially relevant.

Regenative Labs’ AmnioText™, a dehydrated amniotic membrane allograft, was used to close a grade 5 wound according to the Curative Health Services (CHS wound grade scale), described as full thickness and subcutaneous tissues, exposed tendons, ligaments, and/or joints, plus necrotic tissue in the wound, in 7 weeks. Grade 5 wounds have a 91.5% rate of not healing at all. This unsettling outcome emphasizes the efficacy and importance of amniotic membrane allografts in revolutionizing the standard of care for DFUs.

The inability to heal DFUs presents a severe danger to patients as anywhere from 5 to 24% of untreated DFUs can lead to limb amputation within 6–18 months. These infections can lead to long-term impairment and possible lower-limb amputation without timely and correct management.

“Regenative Labs and our products are focused on ameliorating this problem with our outcomes-based approach. We provide the highest quality amniotic membrane allograft to allow doctors to provide predictable outcomes for their patients,” shared Regenative Labs CEO, Tyler Barrett.

Amniotic membrane allografts, such as those provided by Regenative Labs, have proven to augment the body’s ability to regenerate the structural tissue defects associated with DFUs; they are also comparable in cost to the standard of care, which averages about USD 17,245. Not only is the current standard of care for DFUs less effective, but it is also high in cost and typically relies on inpatient expenditures.

Medicare now recognizes the medical necessity of amniotic membrane allografts in the treatment of both DFUs and venous stasis ulcers. Consequently, many patients rely on Medicare to assist with the costs associated with DFU treatment. This presents the opportunity for human amniotic membrane allografts to be utilized in rural and underserved communities where DFU treatment is typically delayed due to high costs and a lack of supplies associated with traditional treatment. This could exponentially decrease the risk of amputations in diabetic patients in these rural and underserved communities.

About Regenative Labs: Regenative Labs produces regenerative medicine products to address the root cause of a patient’s conditions using Wharton’s Jelly innovations rather than masking the pain with other treatments. Regenative Labs works closely with scientists, physicians, hospitals, and surgery centers to constantly monitor and improve patient progress and outcomes for new product development. Formed by veteran industry professionals familiar with daily challenges of innovations in healthcare, the company provides effective, non-addictive, non-invasive options for patients. Regenative Labs has a laser-focused, expert product research and development team which follows FDA guidelines of minimal manipulation for homologous use. The company adheres to AATB and FDA guidelines.

Learn more at Regenative’s website: www.regenativelabs.com

SOURCE Regenative Labs

New research being presented at the European Association for the Study of Diabetes (EASD), held online this year (27 Sept-1 Oct), reveals how Belgium’s efforts to maintain a diabetic foot care program during the COVID-19 pandemic can offer valuable lessons to the rest of the world … “Thanks to the great efforts of diabetic foot clinics, continued availability of diabetic foot ulcer services during lockdown, although in a limited capacity, were really helpful, and may be the reason why we didn’t see late presentation and the impact on the severity of ulcers was limited to slightly larger wounds”, says lead author Dr. An-Sofie Vanherwegen from Sciensano … read more

Role in Pathogenesis and Interest in Diagnosis

Infection of foot ulcers is a common, often severe and costly complication in diabetes. Diabetic foot infections (DFI) are mainly polymicrobial, and Staphylococcus aureus is the most frequent pathogen isolated. The numerous virulence factors and toxins produced by S. aureus during an infection are well characterized. However, some particular features could be observed in DFI. The aim of this review is to describe the role of S. aureus in DFI and the implication of its toxins in the establishment of the infection. Studies on this issue have helped to distinguish two S. aureus populations in DFI: toxinogenic S. aureus strains (harboring exfoliatin-, EDIN-, PVL- or TSST-encoding genes) and non-toxinogenic strains. Toxinogenic strains are often present in infections with a more severe grade and systemic impact, whereas non-toxinogenic strains seem to remain localized in deep structures and bone involving diabetic foot osteomyelitis. Testing the virulence profile of bacteria seems to be a promising way to predict the behavior of S. aureus in the chronic wounds … read more

Here’s a story about a foot ulcer and it’s tragic result in a diabetic with several other health problems. This is an attempt to inform people with diabetes about the vital necessity of foot inspection and care. It goes like this … Someone familiar, who will be Uncle Al for this yarn, had his left foot and lower leg amputated because of a diabetic foot ulcer he didn’t even know he had, because he never looked. Uncle Al has been a very happy fellow throughout his life. He had known he has diabetes for quite a while. He also has had a heart attack, and more lately congestive heart failure of controllable nature — if he watches it … read more

Diabetic ulcers commonly result from high blood sugar damaging nerves, which takes away feeling from the toes or feet … Without the ability to feel pain, hits and bumps tend to go unnoticed and skin tissue breaks down, forming ulcers … A lot of sugar in the bloodstream, along with dried skin as a consequence of diabetes, further slow the ulcer healing process … Recently, Purdue researchers developed a shoe insole that could help make the healing process more portable for the 15% of Americans who develop ulcers as a result of diabetes … The researchers used lasers to shape silicone-based rubber into insoles, and then create reservoirs that release oxygen only at the part of the foot where the ulcer is located … read more

Diabetic foot ulcerations—open sores or wounds that refuse to heal—are a devastating complication affecting more than 15 percent of people with diabetes and resulting in more than 70,000 lower extremity amputations per year in the United States alone. Notably, more than half of patients undergoing amputations due to diabetic foot ulcerations are expected to die within five years—a mortality rate higher than most cancers. Yet, the biological processes at work in diabetic foot ulcerations are poorly understood … read more

     in the UK, Denmark, and Sweden: An observer-masked, randomised controlled trial

The LeucoPatch device uses bedside centrifugation without additional reagents to generate a disc comprising autologous leucocytes, platelets, and fibrin, which is applied to the surface of the wound. We aimed to test the effectiveness of LeucoPatch on the healing of hard-to-heal foot ulcers in people with diabetes … This was a multicentre, international, observer-masked, randomised controlled trial of people with diabetes and a hard-to-heal foot ulcer done in 32 specialist diabetic foot clinics in three countries (UK, Denmark, and Sweden). After a 4-week run-in period, those with a reduction in ulcer area of less than 50% were randomly allocated (1:1) by computer-generated, web-based randomisation … read more

Read the full article on The Lancet Diabetes & Endocrinology

     the UK, Denmark, and Sweden: an observer-masked, randomised controlled trial

The LeucoPatch device uses bedside centrifugation without additional reagents to generate a disc comprising autologous leucocytes, platelets, and fibrin, which is applied to the surface of the wound. We aimed to test the effectiveness of LeucoPatch on the healing of hard-to-heal foot ulcers in people with diabetes … Methods … This was a multicentre, international, observer-masked, randomised controlled trial of people with diabetes and a hard-to-heal foot ulcer done in 32 specialist diabetic foot clinics in three countries (UK, Denmark, and Sweden). After a 4-week run-in period, those with a reduction in ulcer area of less than 50% were randomly allocated … read more

medwireNews: Early intensive glycemic control may reduce the long-term risk for foot ulcers in people with type 1 diabetes, suggest data from the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) study … The DCCT included 1408 people with type 1 diabetes who completed an average of 6.5 years of intensive (target glycated hemoglobin [HbA1c] <6.05% [42.6 mmol/mol]) or conventional (no specific glycemic target) diabetes treatment and subsequently underwent 23 years of follow-up in the EDIC study … During this period, 195 participants developed at least one diabetic foot ulcer (48 people had multiple events) and 36 needed lower extremity amputation … read more

Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose pathogenesis remains incompletely understood. Here, we profile 174,962 single cells from the foot, forearm, and peripheral blood mononuclear cells using single-cell RNA sequencing. Our analysis shows enrichment of a unique population of fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 and increased M1 macrophage polarization in the DFU patients with healing wounds. Further, analysis of spatially separated samples from the same patient and spatial transcriptomics reveal preferential localization of these healing associated fibroblasts toward the wound bed as compared to the wound edge or unwounded skin … read more

     may be mediated through differential gene expression

Negative pressure wound therapy (NPWT) has been successfully used as a treatment for diabetic foot ulceration (DFU). Its mechanism of action on the molecular level, however, is not fully understood. We assessed the effect of NPWT on gene expression in patients with type 2 diabetes (T2DM) and DFU … The final cohort encompassed 21 patients treated with NPWT and 8 with standard therapy. The groups were similar in terms of age (69.0 versus 67.5 years) and duration of T2DM (14.5 versus 14.4 years). We identified four genes differentially expressed between the two study arms post-treatment, but not pre-treatment: GFRA2 (GDNF family receptor alpha-2), C1QBP (complement C1q binding protein), RAB35 (member of RAS oncogene family) and SYNJ1 (synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1) … read more

One fourth of the approximately 22.3 million patients with diabetes in the United States are expected to develop a diabetic foot ulcer (DFU) at some point during their lives, and it is estimated to affect 1-8% of individuals with diabetes annually. DFUs have shown to be challenging to treat, and often result in extended hospital stays, increased risk of infection, and subsequent amputation in certain patients. A major concern regarding amputees is a 5-year mortality rate that rivals that of patients with colon cancer. In addition, DFUs contribute heavily to the financial load of payers, with an estimated annual medical cost of up to $13 billion.

Prior studies have indicated that wounds that penetrate bone, are prolonged and recurrent, and those associated with peripheral vascular disease pose a great risk for eventual amputation. Studies have shown that, even with proper care of DFUs by podiatric physicians and other clinical personnel, these wounds are slow to heal. Advanced therapies are often explored to improve outcomes.

read more

A new screening tool developed by St. Joseph’s Health Care London could reduce the number of diabetes-related amputations across the region … The primary care diabetes support program (PCDSP) at St. Joseph’s partnered with the South West Local Health Integration Network (LHIN) to come up with a standardized screening, assessment and referral tool for family doctors. The tool helps to identify red flags in patients that could lead to devastating foot ulcers … “The end game is early identification and effective intervention of those at risk of diabetes-related foot ulcers,” said Betty Harvey, a nurse practitioner and clinical nurse specialist with the PCDSP. “Once a person has a foot ulcer … read more

in Partnership with CUBRC, Inc. to Advance Topical Pravibismane

Funding will support exploratory phase 2 proof-of-concept study in patients hospitalized for moderate to severe diabetic foot ulcer infection (DFI)

BOZEMAN, Mont. and VANCOUVER, BC, June 7, 2022 /PRNewswire/ – Microbion Corporation of Bozeman, MT, today announced that it has received non-dilutive funding through its strategic partnership with CUBRC, Inc., a Buffalo-based, independent not-for-profit research company, of up to $2.1 million from the US Navy through the Medical Technology Enterprise Consortium (MTEC) partnership. The funding project is titled “Pravibismane Suspension as a Topical, Broad Spectrum Anti-Infective Wound Care Treatment and Prevention for Combat Injury-Related Infections”. The funding received will be used to support the conduct of an exploratory phase 2 proof of concept trial in patients hospitalized for moderate to severe diabetic foot ulcer infection with enrollment expected to begin in Q2 2022.

“We are pleased to be supported by the US Navy and MTEC and are working closely with them to advance our topical pravibismane through phase 2 proof-of-concept studies,” said Karim Lalji, CEO of Microbion Pharma Corp. “Our topical diabetic foot ulcer infection program is well aligned to the Navy’s interest in innovative wound care technologies to treat and prevent biofilm-related infections, since biofilm contamination is a hallmark characteristic of chronic foot ulcer infections. Further exploration of pravibismane’s safety and efficacy in overcoming biofilm-related DFI may potentially expand the clinical utility of topical pravibismane to treat combat wound infections in a variety of settings, including in the field and hospital.”

Lester Martinez, MD, MPH, Major General (Retired), U.S. Army, President and Chairman of MTEC Board commented on the importance of Microbion’s research. “Though diabetic foot ulcer infections aren’t traditionally thought of as a combat related wound suffered in the field, diabetes is a serious disease that affects a significantly high percentage of our veterans and its complications such as DFI contributes to decline in health, quality of life and are responsible for the vast majority of non-combat amputations among veterans. Microbion’s research into healing these wounds with the ultimate goal of preventing or delaying amputations can potentially improve the daily lives of these patients and return normal mobility,” Dr. Martinez stated.

Pravibismane is the first in a new class of anti-infective drugs structurally unrelated to other clinically utilized antibiotics. With a novel mechanism of action, pravibismane shuts down bacterial ATP production thereby halting global bacterial cellular metabolism. In in vitro studies, pravibismane exhibits broad-spectrum, potent activity against DFI-relevant pathogens and their biofilms including MRSA and drug resistant P. aeruginosa.

In a randomized, double-blind, placebo-controlled Phase 1b trial treating patients with chronic moderate to severe diabetic foot ulcer infection, topical pravibismane treatment plus standard of care demonstrated a numeric 85% wound size reduction versus 30% placebo plus standard of care. Pravibismane also demonstrated a numeric reduction in ulcer-related amputation (2.6% in the pravibismane group vs 15.4% placebo).

DFIs are a major health concern in the Veterans Health Administration as DFUs are associated with a substantial mortality rate (five-year mortality rates are as high as 45% for neuropathic ulcers and 55% for ischemic ulcers1) and often require amputation to fully address the nidus of infection.2 Approximately 28.5 million adults in the US are diagnosed with diabetes, of whom 15 – 25% are at risk of developing a foot ulcer.3,4 More than half of diabetic foot ulcers become infected.5 DFIs remain the most frequent diabetic complication requiring hospitalization and are the most common precipitating event leading to lower extremity amputation.6 Furthermore, recent studies suggest that many DFIs are caused by bacteria in a biofilm mode.6 In 2018, there were ~8.25 million hospital discharges with diabetes reported, including 154,000 for a lower-extremity amputation.3 US Veterans Affairs estimates there were 20.3 million living Veterans in 2018.7 The overall prevalence of diabetes among US veterans is ~25%, which is higher than the US civilian population at ~9%.8

References:

1. Del Core MA, Ahn J, Lewis RB, et al. The evaluation and treatment of diabetic foot ulcers and diabetic foot infections. Foot & Ankle Orthopaedics. 2018;3:3. doi:10.1177/2473011418788864
2. Sundararajan PP, Porter BM, Grant KA, et al. Foot infections in the Veterans Health Administration. The Foot and Ankle Online Journal. 2015;8(3):1. doi:10.3827/faoj.2015.0803.0001
3. Centers for Disease Control and Prevention. National Diabetes Statistics Report website. https://www.cdc.gov/diabetes/data/statistics-report/index.html, accessed June 6, 2022
4. Lavery LA, Davis KE, Berriman SJ, et al. WHS guidelines update: Diabetic foot ulcer treatment guidelines. Wound Repair Regen. 2016;24(1):112–26. doi: 10.1111/wrr.12391
5. Armstrong, DG, Boulton, AJM, and Bus, SA. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376:2367-75. doi: 10.1056/NEJMra1615439
6. Lipsky et al. Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update). Diab Metab Res Rev. 2020. e3280. doi: 10.1002/dmrr.3280
7. VETPop2018: A Brief Description. Web: https://www.va.gov/vetdata/docs/Demographics/New_Vetpop_Model/VP_18_A_Brief_Description.pdf, accessed June 6, 2022
8. Liu Y, Sayam S, Shao X, et al. Prevalence of and trends in diabetes among veterans, United States, 2005–2014. Prev Chronic Dis. 2017;14:170230. doi: 10.5888/pcd14.170230

About Microbion
Microbion is a clinical-stage pharmaceutical company developing a new class of therapeutic compounds to improve the lives of patients with rare and serious diseases. Microbion’s lead drug candidate, pravibismane, is the first product in this new class and has a novel mechanism of action offering unique potential to address the unmet needs of chronic and severe health conditions. The Company is advancing inhaled pravibismane in Phase 1 clinical development for the treatment of chronic lung diseases, including non-tuberculous mycobacteria (NTM) and cystic fibrosis-related lung infections. Topical/local pravibismane is in Phase 2 development for the treatment of chronic wounds and orthopedic infections. Pravibismane has received backing from the Cystic Fibrosis Foundation, NIH, US DoD, and CARB-X with over $21 million in grants. The FDA has granted pravibismane with Orphan Drug, Fast Track, and QIDP designations. Microbion Pharma Corp. is a wholly owned subsidiary of Microbion Corporation. For more information visit: www.microbioncorp.com.

About CUBRC
CUBRC is an independent not-for-profit scientific corporation that executes Research, Development, Testing and Systems Integration programs in Medical Sciences, Chemical and Biological Defense, Data Science and Information Fusion, Command and Control, and Hypersonics. For more information visit: www.cubrc.org.

Safe Harbor Statement
Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the success of clinical development of pravibismane and preparation for potential commercialization. These statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: our ability to enroll patients in our clinical trials at the pace that we project; the size and growth of the potential markets for pravibismane or any future product candidates and our ability to serve those markets; our ability to obtain and maintain regulatory approval of pravibismane or any future product candidates; and our expectations regarding the potential safety, efficacy or clinical utility of pravibismane or any future product candidates. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Microbion Corporation disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

US Government Funding Disclaimer
Efforts described herein were partially sponsored by the Government under Other Transactions Number W81XWH-15-9-0001. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of the U.S. Government.

SOURCE Microbion Corporation

This article was originally published here

Findings from a New Clinical Study Using MolecuLight Imaging of Diabetic Foot Ulcers Prompts New Diagnostic Terminology Enabling Proactive Infection Management

TORONTO, Feb. 14, 2023 /PRNewswire/ – MolecuLight Inc., the leader in point-of-care fluorescence imaging that locates and detects elevated bacterial loads in and around wounds, announced the publication of “Point-of-care fluorescence imaging reveals extent of bacterial load in diabetic foot ulcers“1 in International Wound Journal. The publication reports on the analysis of 138 diabetic foot ulcer wounds, highlighting the frequent presence of healing delays and elevated bacterial burden as identified through standard clinical assessment, fluorescence imaging (MolecuLight i:X®), and quantitative microbiology.

Chronic inhibitory bacterial load (“CIBL”) on the bacterial-infection continuum. Based on the International Wound Infection Institute (IWII) 2022 wound infection continuum (CNW Group/MolecuLight)

The emergence of data on the link between bacterial load and healing over the last decade, together with this current study, prompted study authors David G. Armstrong, Michael E. Edmonds, and Thomas E. Serena to define new clinical terminology, chronic inhibitory bacterial load (CIBL). CIBL is defined as “the chronic presence of bacterial microorganisms in a wound or its surrounding tissue at loads which can damage tissues and be inhibitory to healing, as well as require clinical intervention, with or without the presence of clinical symptoms”.

MolecuLight fluorescence imaging is currently the only way to detect and locate CIBL at the point of care. This term enables the proactive diagnosis of CIBL early along the bacterial-infection continuum, to facilitate its targeted removal, promote healing, and prevent the sequelae of infection in frequently asymptomatic diabetic ulcers.

Key findings of the study include:

• Less than 12% of diabetic ulcers exhibited clinical symptoms of bacteria and infection, despite the presence of loads >10⁴ CFU/g in over 90% (average bacterial load of 10⁸ CFU/g). Even as bacterial loads increased up to >10⁸ CFU/g, detection of clinical signs and symptoms of infection did not increase.
• Bacterial loads >10⁴ CFU/g can preclude wounds from healing through various biological mechanisms and are contraindicated for many advanced therapies. This study showed that the occurrence of delayed healing increased alongside bacterial load.
• Fluorescence imaging using MolecuLight increased sensitivity for the detection of CIBL across loads 10⁴–10⁹ (p < .0001), peaking at 92.6% for bacterial loads >10⁸ CFU/g. This was 8.3 times superior to standard clinical assessment alone.
• Fluorescence imaging further showed that 84.2% of ulcers contained high loads in the periwound region, an area that is frequently overlooked.

Infection prevention is a key goal of CIBL’s introduction, adoption, and management. CIBL is the result of these seasoned wound care clinicians’ long-time advocacy for proactive wound management as they see firsthand the devastating consequences of delayed treatment. “Infection is the greatest destroyer of the diabetic foot. It is the final common pathway for most amputations, and we need to fight it as early as possible in its natural history”, says Dr. Michael E. Edmonds, one of the paper’s authors and Consultant of Diabetologist at the Diabetic Foot Clinic, King’s College Hospital Foundation Trust in London, UK. “CIBL localization and proactive management is a crucial strategy in reducing unnecessary amputations and saving lives”, he concludes.

As MolecuLight is the only device capable of detecting elevated bacterial loads in wounds in real-time, regions of CIBL can be non-invasively and accurately detected and mapped. The device provides clinicians with immediate feedback to guide their therapeutic decision-making process in a number of clinical settings from the outpatient clinic to the operating room. Multiple routine procedures are enhanced by its proven capabilities, such as debridement, wound hygiene, and preparation for advanced therapies resulting not only in better outcomes,3,4 but more rational resource consumption and antimicrobial stewardship.4

“There is also a meaningful role for fluorescence imaging with MolecuLight in antimicrobial stewardship. This is critical considering that approximately 70% of patients with diabetic foot ulcers are prescribed antibiotics at some point during their care, and over 80% are prescribed antimicrobial dressings3, often in a haphazard manner”, says Dr. Thomas Serena, study author and the Founder and Medical Director of The SerenaGroup®. “Diagnostic uncertainty has been listed as a key factor in antibiotic overuse in wound care. Fluorescence signals as a real-time imaging biomarker of CIBL could enable clinicians to more effectively leverage hygiene-based strategies to remove bacteria rather than resorting to antibiotics”.

“The definition of an infection’s genesis and its resolution is a clinical one”, notes Dr. David G. Armstrong, study author, Professor of Surgery at the University of Southern California, and founder and co-Director of the Southwestern Academic Limb Salvage Alliance (SALSA). “The problem is that many objective local signs may be blunted in the chronic wound and it is likely that we are not yet effectively measuring what we manage. Fluorescence imaging of chronic inhibitory bacterial load (CIBL) is positioned to potentially change contemporary paradigms of wound management. We are hopeful that this new clinical term, CIBL, can be a key indicator to enable pre-infection intervention such as debridement or modification of wound therapy.”

The MolecuLight i:X and DX are the only imaging devices for the real-time detection of elevated bacterial burden in wounds that are FDA cleared and CE and Health Canada approved. With clinical evidence including over 65 peer-reviewed publications involving 1,500 patients, they are used by leading wound care facilities globally.

References
1 Armstrong DG, Edmonds ME, Serena TE. Point-of-care fluorescence imaging reveals extent of bacterial load in diabetic foot ulcers. Int Wound J. 2023;20(2):554-566
2 Wounds International (2022) International Consensus Update 2022 International Wound Infection Institute (IWII) Wound Infection in Clinical Practice: Principles of best practice. Available from https://woundinfection-institute.com/
3 Price N. Routine fluorescence imaging to detect wound bacteria reduces antibiotic use and antimicrobial dressing expenditure while improving healing rates: retrospective analysis of 229 foot ulcers. Diagnostics (Basel). 2020;10(11):927.
4 Rahma S, Woods J, Nixon JE, Brown S, Russell DA. The use of point-of-care bacterial autofluorescence imaging in the Management of Diabetic Foot Ulcers: a pilot randomised controlled trial. Diabetes Care. 2022;45:1601-1609.

About MolecuLight Inc.
MolecuLight Inc. is a privately-owned medical imaging company that has developed and is commercializing its proprietary fluorescent imaging platform technology in multiple clinical markets. MolecuLight ‘s suite of commercial devices, which include the MolecuLight i:X® and DX™ fluorescence imaging systems and their accessories, are point-of-care handheld imaging devices for the real-time detection and localization of bacterial load in wounds and digital wound measurement. MolecuLight procedures performed in the United States benefit from an available reimbursement pathway which includes two CPT® codes for physician work to perform “fluorescence imaging for bacterial presence, location, and load” and facility payment for Hospital Outpatient Department (HOPD) and Ambulatory Surgical Center (ASC) settings through an Ambulatory Payment Classification (APC) assignment. The company is also commercializing its unique fluorescence imaging platform technology for other global markets with relevant unmet needs in food safety, consumer cosmetics and other key industrial markets.

SOURCE MolecuLight

     to Skin Temperature Monitoring in Journal of Medical Internet Research (JMIR)

— Paper details results of first at-home, continuous, wireless temperature monitoring system to detect onset of diabetic foot ulcers caused by neuropathy

— Temperatures measured by standalone sensors were within 0.2℃ of the reference standard

–Data demonstrates potential as promising approach for early warning of foot ulcers, Charcot foot, and re-ulceration

SAN FRANCISCO–(BUSINESS WIRE)–Siren, the health technology company that developed Neurofabric™, a machine-washable, machine-dryable smart textile with built-in sensors, today announced publication of a foundational paper supporting its approach in Journal of Medical Internet Research (JMIR), the leading peer-reviewed journal for digital medicine, and health & healthcare in the Internet age. In the paper, a team of international researchers led by Ran Ma, co-founder and CEO, and Alexander M Reyzelman, DPM; Samuel Merritt University, detail the role of Siren’s Diabetic Sock and Foot Monitoring System in maintaining continuous, wireless skin temperature monitoring for users at-home, demonstrating the potential for the reduction of foot ulceration for diabetic patients.

“Diabetic foot ulcers (DFU) result in considerable cost to the healthcare system when immediate ulcers, social services, home care, and subsequent ulcers are taken into consideration,” said Alexander M Reyzelman, DPM; Samuel Merritt University and lead author on the paper. “The cost per ulcer is over $33,000 per year and the cost per leg amputation is more than $100,000 per year. Over 100,000 legs are lost to diabetes each year. In diabetic foot complications such as foot ulcers, elevated temperatures in regions of the foot have been shown to be a precursor for ulceration.”

The JMIR publication details Siren’s pilot study of its Diabetic Sock and Foot Monitoring System to assess how comfortable their sensor-embedded socks were for daily use, and whether observed temperatures correlated with clinical observations.

In the study, patients wore the socks at home for a median of 7 hours, reporting that they felt just like their normal, everyday socks. Their stated willingness to wear the socks every day underscores the socks’ suitability for home use, suggesting that Neurofabric can seamlessly integrate into the life of the wearer.

“Several tools have been developed to measure plantar temperatures and the progression of foot ulcers, but they only measure temperature once a day which can lead to false-positives, or are only available for in-clinic use and not at home,” said Ran Ma, co-founder and CEO of Siren. “Now, for the first time, we highlight the striking connection between our Neurofabric’s powerful ability to capture data at home, every single second. The data is incredibly meaningful—it’s the largest amount of patient data that physicians have had wireless access to in real-time. This solidifies the potential for Neurofabric to change the trajectory of diabetic foot ulcerations and the many complications that can occur from it—including sepsis, and lower limb amputations.”

Patients also reported that Siren’s mobile app was easy to use and navigate. Through the mobile app, wearers can view the current temperature as measured at six points on the user’s foot. While the app was not set up to generate alerts in this study, users can receive a notification on their phone when a temperature increase is detected between contralateral positions.

“Digital health is a vast and burgeoning field and spans several aspects of health management—Neurofabric can facilitate the management of chronic conditions at home, including the effective and timely management of DFUs,” said Henk Jan Scholten, co-founder and COO of Siren. “The JMIR publication sheds light on both the ability of these Neurofabrics to improve quality of life for diabetes patients, and Siren’s first use-case to empowering people to take their health into their own hands.”

Siren is initiating a large-scale patient study in 2019.

Read the JMIR paper in full here: Continuous Temperature-Monitoring Socks for Home Use in Patients With Diabetes: Observational Study

About Siren

Founded in August 2016, Siren is a health technology company and the maker of Neurofabric™, machine-washable, machine-dryable smart textiles. Siren’s first product, Siren Diabetic Socks, are designed to help people with diabetes avoid amputations. Siren was previously named AARP Consumer’s Choice Award winner, 2017 CES TechCrunch Hardware Battlefield, 2018 CES Best of Innovation, Fast Co.’s 2018 Innovation by Design Award Honorable Mention, and 2018 ADA Healthtech Showcase winner. Siren’s investors include DCM, Khosla Ventures and Founders Fund.

press release from BusinessWire

Researchers in Michigan have developed a novel nitric oxide sensing device, providing new insight into the causes of diabetic foot ulcers and possible avenues for treatment … Approximately 9 to 26 million diabetic patients around the world develop foot ulcers every year. These ulcers can double the risk of death for diabetic patients and may take up to 120 days to heal. Previous research has suggested that the impaired healing associated with diabetic foot ulcers is caused by unregulated levels of nitric oxide. Measuring live concentrations of this compound has posed a significant challenge due to its highly reactive nature. Previous studies have used nitrite, a stable byproduct, to measure nitric oxide levels indirectly … read more

Protein–energy malnutrition is known to be involved in wound healing. While wound healing in patients with diabetic foot ulcers (DFU) is a complex and multifactorial process, the role of malnutrition in this case has rarely been explored. The objective of this study was to determine whether the nutritional status of diabetic patients influences the healing of DFU … 48 patients were included in this prospective, single-center study. All patients with comorbidities or factors involving malnutrition or influencing biological measurements were excluded. Patients were followed up for 24 weeks … read more at Acta Diabetologica (purchase required)

Diabetic foot ulcers are a major health and economic global burden, but ultimately, at least in theory, they’re preventable. The re-ulceration rate is as high as 65% within 5 years, and among persons who initially present with a diabetic foot ulcer, up to 25% may require amputation … One of the most important risk factors for diabetic foot ulceration is diabetic peripheral neuropathy. This involves loss of sensory perception, haptic feedback, and pain perception, so patients can’t self-regulate their foot pressures. It’s thought that these high foot pressures over time cumulatively contribute to the development of diabetic foot ulcers … read more