Sesamol incorporated cellulose acetate-zein composite nanofiber membrane: An efficient strategy to accelerate diabetic wound healing.

Recently, the function of nanofiber membranes prepared from electrospinning in accelerating wound healing has attracted wide attention. In this study, novel nanofiber membranes consisted of cellulose acetate (CA) and zein were fabricated to provide efficient delivery vehicles for sesamol, then the effect of sesamol-loaded composite nanofiber membrane on the wound healing process for diabetic mice was studied. It was found the critical concentration of CA was between 15% and 25% (w/v), and the most suitable concentration of stabilizing fibers was 22.5%. When the CA/zein ratio was 12:8, the fiber obtained the small diameter and uniform distribution, the stable intermolecular structure, the low infiltration speed and high stability in water. The composite nanofiber membrane with high-dose sesamol (5% of total polymer concentration, w/w) promoted formation of myofibroblasts by enhancing TGF-β signaling pathway transduction, and promoted keratinocyte growth by inhibiting chronic inflammation in wounds, thus enhancing wound healing in diabetic mice. This study could further broaden the application range of sesamol, CA and zein, and provide reference for the design and development of new wound dressings in the future.

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Progettazione di una medicazione colloidale antinfiammatoria e adesiva per il trattamento delle ferite.

Materiali medicazione sono ampiamente utilizzati per proteggere le ferite dall’esterno dell’ambiente e per promuovere la ferita guarigione. Tuttavia, le medicazioni per ferite convenzionali mancano di proprietà adesive dei tessuti e di funzioni antinfiammatorie, che portano a fibrosi e stenosi, in casi come ferite gastrointestinali dopo chirurgia endoscopica. Nel presente studio, riportiamo le proprietà adesive e antinfiammatorie dei tessuti di una medicazione composta da particelle di gelatina modificate con corticosteroidi. L’idrocortisone (HC), che è una classe di corticosteroidi antinfiammatori, è stato usato per modificare la gelatina di pollock dell’Alaska (ApGltn) per sintetizzare l’ApGltn modificato con HC (HC-ApGltn). Le microparticelle (MP) di HC-ApGltn sono state fabbricate aggiungendo etanolo in soluzione acquosa HC-ApGltn ed eseguendo la reticolazione termica (TC) senza l’uso di tensioattivi tossici e reagenti di reticolazione. La modifica di ApGltn con HC idrofobo contenente la struttura della spina dorsale del colesterolo ha migliorato la sua forza di adesione ai tessuti sottomucosi gastrici in condizioni umide a causa di interazioni idrofobiche. Questa ritenzione della proprietà adesiva in condizioni di bagnato consente una protezione stabile delle ferite dall’ambiente esterno. Abbiamo scoperto che gli MP di HC-ApGltn sono stati ripresi dai macrofagi e hanno efficacemente soppresso i cambiamenti morfologici dei macrofagi attivati ​​da LPS e il livello di espressione della citochina infiammatoria. Adesivi per tessuti robusti e MP anti-infiammatori possono servire da medicazione avanzata in grado di proteggere le ferite e sopprimere le risposte infiammatorie per promuovere la guarigione delle ferite. Questa ritenzione della proprietà adesiva in condizioni di bagnato consente una protezione stabile delle ferite dall’ambiente esterno. Abbiamo scoperto che gli MP di HC-ApGltn sono stati ripresi dai macrofagi e hanno efficacemente soppresso i cambiamenti morfologici dei macrofagi attivati ​​da LPS e il livello di espressione della citochina infiammatoria. Adesivi per tessuti robusti e MP anti-infiammatori possono servire da medicazione avanzata in grado di proteggere le ferite e sopprimere le risposte infiammatorie per promuovere la guarigione delle ferite. Questa ritenzione della proprietà adesiva in condizioni di bagnato consente una protezione stabile delle ferite dall’ambiente esterno. Abbiamo scoperto che gli MP di HC-ApGltn sono stati ripresi dai macrofagi e hanno efficacemente soppresso i cambiamenti morfologici dei macrofagi attivati ​​da LPS e il livello di espressione della citochina infiammatoria. Adesivi per tessuti robusti e MP anti-infiammatori possono servire da medicazione avanzata in grado di proteggere le ferite e sopprimere le risposte infiammatorie per promuovere la guarigione delle ferite.

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Pertinent Pearls In Coding For Wound Care Services

With the ongoing increase in available wound care products and services, this author discusses how to approach coding for these complex cases. 

Wound care is a large part of many podiatry practices today. There has been an explosion of wound care products and techniques that we may utilize in trying to treat the stubborn wounds we deal with on a day-to-day basis. Unfortunately, with the increased volume and cost of these items comes increased scrutiny of how and when we use these products and services. It is important to understand the most common aspects of billing and coding for wound care in order to succeed for both your practice and your patients.

Wounds can be very complicated with frequent and ongoing reevaluation of treatment outcomes. Some wounds go on to heal with simple measures and we are primarily monitoring progress until healing is eventually complete. These two scenarios differ from one another when considering proper coding. When billing an evaluation and management service (E&M) at the same encounter for which you are billing a procedure (such as debridement), there must be a significant and separately identifiable E&M service from the procedure in order to be paid for both services. This would require taking a history, performing an examination and then eventual decision-making. These three key components are the basis for an E&M service.

Remember that for a follow-up E&M service to be eligible for payment, you must document two of the three E&M components as being significant and separately identifiable. Also, for every procedure, there is an “E&M” portion built into the allowed fee. In this instance, one must document and show that there is more history, examination and decision making than would be included in the fee allowance for the procedure.

For example, a patient presents to your office with a new wound. You obtain a history of the wound, examine the wound and then decide what treatment to pursue. You also perform an in-office debridement. As a result, at this initial presentation of the wound an E&M service would be appropriate in addition to the procedure. The level of E&M service billed would NOT necessarily be based solely upon the complexity of the wound (e.g. exposed bone) but rather the level of each key component performed and the resulting level of documentation in your chart. As always, charting is key.

The patient then returns the next week for a follow-up visit. If there are no significant history or examination changes from the previous visit and the wound is progressing as expected, then there may not be an eligible E&M service separate from any procedure that one may also perform on that day. However, if at a subsequent visit, the physician needs to alter the wound care protocol (if the wound is deteriorating and additional imaging is necessary, or one needs to initiate or change antibiotic therapy), then an E&M service would be appropriate to bill based upon your level of documentation. The chart notes would need to document the changes that occurred since the last encounter and the associated decision-making.

Benefits And Pitfalls Of EHRs In E&M Documentation

With many office EHRs, there is the ability to bring information forward from previous patient encounters. This can be deemed templating or cloning of charts, but this is a double-edged sword. EHR-associated templating can make our lives easier when it comes to documentation and completeness of a chart note. However, you cannot use patient data or information brought forward from a previous chart note to augment your current chart note just to bill an E&M service, or a higher level of service.

Simply cutting and pasting the history from week to week does not meet proper documentation requirements. You would only get “credit” for any history that has changed since the last encounter. Similarly, if the examination is unchanged except for the fact the wound is getting smaller and progressing as expected, then there is no real “credit” there either. Lastly if your decision making is essentially to “continue with current treatment course,” there is no added consideration there as well. Without documentation of changes in history, additional examination or decision making (at least two of three components), there is no additional E&M service to bill. Lastly, be very careful with templates as one may inadvertently bring charting errors forward as well that can make your chart look poor and clearly templated.

Key Concepts In Coding For Wound Debridement

Debridement is a common part of the treatment algorithm for wounds. There are two debridement code series, Current Procedural Terminology (CPT) 9759X and 1104X, that clinicians can utilize. CPT series 9759X involves selective debridement of epidermal and dermal tissue, and superficial biofilm. CPT series 1104X involves the excisional debridement of deeper tissue including subcutaneous tissue, muscle, tendon or bone. One also needs to clearly identify the type of tissue he or she has debrided in the chart notes.

In addition, proper documentation should include the location of the wound, the size of the wound, the instruments one uses for debridement, if anesthesia is required and the type and anatomic depth of debridement. Additionally, examination documentation should include the condition and characteristics of the wound bed as well as notation on any drainage, odor or cellulitis.

We often see multiple wounds on the feet and selection of the appropriate code is based upon the aggregate size of similar wounds, not on a right foot or left foot basis. Remember that wound codes are not foot specific. They apply to the entire body. Accordingly, one determines the codes based on the tissue type debrided and these codes are applicable to any body part. Therefore, add up all similar wounds of similar debridement depths and combine them into one code per the appropriate aggregate sizing.

If there are three wounds on a foot, two of which require debridement to subcutaneous tissue and a third wound requires only dermal debridement, the proper coding would be CPT 11042 (debridement of subcutaneous tissue) for the composite two wounds requiring subcutaneous tissue debridement and CPT 97597 (debridement of non-viable tissue) for the third wound, which requires only more superficial selective debridement. Do not use right or left foot modifiers as those are incorrect and will result in your claim being denied. A -59 modifier is necessary to be paid for both debridement codes when you bill them on the same day.

These wound care codes are listed per 20 sq cm. If the aggregate size of similar wounds exceeds that amount, there are add-on codes that clinicians can bill. Accordingly, for the debridement of an aggregate 60 sq cm wound through subcutaneous tissue, CPT 11042 applies for the first 20 sq cm and CPT 11045 (two units in this case) applies for each additional 20 sq cm.

Correct measurement of wounds is important not only to document the presence or absence of improvement, but also to properly select the appropriate CPT debridement code. A wound may be 4 cm in overall diameter but the base of the wound, which has the subcutaneous tissue you are debriding, is only 2 cm in diameter. Billing is based upon the deepest tissue debrided and the amount of that specific tissue in square centimeters. In this scenario, one is debriding two sq cm. Keep in mind that if the wound extends deep to bone but you only debride subcutaneous tissue, the proper billing level would be CPT 11042 (debridement subcutaneous tissue), not CPT 11044 (debridement of bone).

When applying skin substitutes, one needs to perform some basic wound preparation/care prior to the application of the product. This wound preparation may include some tissue debridement. CPT 15271 is used for application of the product on the leg and CPT 15275 for the foot. You cannot bill both CPT series 1527X in combination with either CPT 9759X/1104X series codes as this would be essentially duplicate billing. You can only bill for the wound preparation codes when applying a wound care product. CPT 15271 for application of the product on the leg and CPT 15275 for the foot are designated in 25 sq cm increments. The add-on codes are CPT 15272 (for the leg) and CPT 15276 (for the foot) are used for aggregate wounds greater than 25 sq cm and billed per each 25 sq cm increment. If the wounds were to exceed aggregate 100 sq cm in size, CPT 15273/15274 and CPT 15277/15278 codes are to be used as a single code (i.e you cannot bill CPT 15277 in addition to 15275 and 15276, but these should be rare in the foot and ankle).

Choosing Proper Coding For Skin Substitute Products

The next issue is selection of a skin substitute product. Many products have specific FDA indications. Some are only indicated for diabetic foot wounds or venous leg ulcers. Reimbursement for the use of these products is limited to those indications. If the patient has an ulcer but is not diabetic, some wound care products may not be approved if the indication is only for a diabetic foot wound. Not all products are indicated for exposed bone or tendon, either. Some insurance companies have additional requirements. One example may be in regard to the coverage or lack thereof for small wounds. There may be a minimum one cm diameter wound size requirement, which clinicians need to be aware of. Additionally, some insurances have limitations on the number of times a clinician can use a product without additional authorization.

Each skin substitute product has a specific Q code, which identifies the product. Make sure the product you use is properly identified. Exercise caution if a manufacturer representative tells you to bill his or her company’s product using a certain Q code just because it is “similar” to some other product.

Therefore, when dealing with private insurance carriers, it is important to pre-authorize every wound care product. This applies to both primary as well as any secondary insurance carriers. These products are very expensive and if the product is not allowed for any reason then the facility, provider or patient will be billed in full for the product.

Many patients today have insurance plans with very high deductibles so even though the use of skin substitute and other advance wound care products maybe a covered benefit they may or may not be affordable. Even a 20 percent co-insurance may be out of reach for some patients. Keep this in mind when selecting products for your patient. One may need to make compromises when selecting products based, unfortunately, on financial concerns. In addition to any medical indications, the place of service may also be an issue. Some products are only reimbursable when the application is in an operating room setting versus a private office or wound care center.

The next question is when to start using skin substitutes. That obviously depends on the quality of the base of wound. This documentation is also necessary from a medicolegal aspect as well. If the wound bed is poor, one first needs to perform proper debridement and wound preparation. If there is significant venous insufficiency and edema, physicians need to address that promptly. Other things to consider are addressing out of control hemoglobin A1c levels and overall vascular status. Superficial or systemic infections warrant primary treatment as well. There also needs to be proper offloading. If one does not address these factors, these products, although very effective, can be significantly hindered in their ability to heal wounds.  If the insurance carrier only allows five product applications, then using the product on an improperly prepared wound bed would be wasteful and detrimental to the patient.

Many insurance carriers require some level of more conservative care before initiating the start of skin substitutes or other advanced wound care products. This is obviously controversial. The current standard in wound healing is 50 percent closure of the wound in four weeks. One could make the argument of starting wound care products, such as skin substitutes, as quickly as possible for patients who have high morbidity issues. However, many carriers may want at least four to six weeks of conservative treatment that could include documentation of offloading, local debridement, compression and addressing infectious or metabolic issues. Documentation of wound size and quality is very important in these cases.

If one institutes conservative wound care measures and the wound is showing steady progress with these measures alone, then the question becomes “Should a skin substitute be used at all?” This is an area of discussion right now with various Medicare carriers. If the wound is going to heal on its own based upon addressing factors such as glucose levels, infection, offloading, and compression, then it may very well heal without applying skin substitutes. There needs to be documentation of why, if a wound is healing on its own in a reasonably steady fashion, skin substitutes are required. This is a current area of audit and Medicare scrutiny. If the wound healing has stalled or is progressing very slowly, then proper documentation of this may result in authorization from the insurance carrier and also protect you in the case of an audit.

I personally recommend making patients aware of insurance company regulations and restrictions so they can also help advocate for themselves. This can be helpful when dealing with the insurance company to get authorization for wound care services and products.

Navigating Off-Label Uses For Wound Care Products

There have been many recent audits surrounding wound care products. Many of these audits are related to not using the proper product for the proper type of wound. Newer audits are for non-wound-related uses of skin substitutes. Many products, imaging systems that are commonplace now were at one point off-label. If you are using a skin substitute for an off-label use, make sure you and/or your staff are very clear about the product you are using, and how you will use it when obtaining a pre-authorization.

Physicians are using wound care products in non-wound-related foot surgery to augment tendon repairs and act as an interface between tissue layers to limit adhesions and/or scarring. Unfortunately, I have seen requests for the use of these products in simple hammertoe repairs and even matrixectomies! Be able to prove some level of medical basis for the off-label use of these products in an appeal situation. A surgeon’s personal preference/past experience is not enough.

Also be careful when interacting with manufacturer representatives who may imply proper use of these products in situations that may indeed be inappropriate. This may get you flagged for an audit. Make sure you document the off-label use of the product and that you informed the patient you were using the product off-label. You should have the patient sign a form similar to an ABN stating that he or she acknowledges the off-label use of the product, agrees to pay for the product and that the insurance company will not be billed for it

In Conclusion

Wound care has been an integral part of the podiatric profession for quite some time. This field and its available treatment options has exploded over the past few years. It can be a very professionally rewarding part of your practice. In order to best succeed in the treatment of wounds, make sure you and your staff are well versed in treatment options, product availability, indications and proper billing protocols.

Dr. Poggio is a California Podiatric Medicine Association Liaison to Noridian JE MAC and a medical consultant to several national health insurance and review organizations. He is a member of the American College of Podiatric Medical Reviewers and is board-certified by the American Board of Podiatric Medicine and the American Board of Podiatric Orthopedics and Primary Podiatric Medicine. 

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L’amputazione di piede e gamba correlata al diabete e alla cattiva circolazione è in aumento in Ontario

Il diabete e la malattia dell’arteria periferica (cattiva circolazione) sono responsabili di oltre l’80% delle amputazioni di gambe e piedi in Canada. Il numero di amputazioni di gambe e piedi è in aumento, secondo un nuovo studio condotto da ricercatori Dell’ICES , un istituto di ricerca senza scopo di lucro che utilizza informazioni sulla salute basate sulla popolazione per produrre conoscenze su una vasta gamma di problemi sanitari.

Lo studio pubblicato oggi nel CMAJ ha esaminato i dati su tutti gli individui di almeno 40 anni con una storia di diabete e / o malattia dell’arteria periferica che hanno subito l’amputazione degli arti inferiori tra il 1 ° aprile 2005 e il 31 marzo 2016 in Ontario.

Le amputazioni di piedi e gambe legate al diabete e alla cattiva circolazione sono in aumento in OntarioClicca sull’immagine per ingrandirla

I ricercatori hanno scoperto che 20.062 pazienti con diabete e / o malattia dell’arteria periferica avevano un’amputazione degli arti inferiori. Quasi i due terzi di tali amputazioni (12.786 o 63,7 per cento) erano amputazioni maggiori (sopra la caviglia). 

“Il nostro studio suggerisce che dobbiamo rinnovare e coordinare meglio gli sforzi per prevenire le amputazioni legate al diabete e alla cattiva circolazione”, afferma il dott. Charles de Mestral , autore senior dello studio, scienziato a contratto presso il CIEM e chirurgo vascolare presso l’ospedale di San Michele.

I ricercatori hanno scoperto che i tassi complessivi di amputazioni sono aumentati nell’ultimo decennio, spinti da un aumento delle amputazioni minori (sotto la caviglia), in linea con il numero crescente di persone con diagnosi di diabete in Ontario. 

“La crescente prevalenza di diabete, malattie delle arterie periferiche e l’invecchiamento della popolazione sono alcuni fattori che possono aiutare a spiegare perché abbiamo riscontrato un aumento del numero di amputazioni durante il periodo di studio”, afferma il Dr. Mohamad A. Hussain, autore principale del studio, chirurgia vascolare residente presso l’Università di Toronto.

Il tasso complessivo di qualsiasi amputazione (maggiore o minore) inizialmente è diminuito da un tasso trimestrale di 9,88 per 100.000 persone, fino a 8,62 tra il 2005 e il 2010, ma è aumentato nuovamente dal 2016 a 10 per 100.000 persone.

“Per le persone con diabete, l’amputazione degli arti inferiori è considerata una delle conseguenze più temute e debilitanti della malattia”, afferma il dott. Jan Hux , presidente e CEO di Diabetes Canada. “I tassi crescenti di complicanze del piede diabetico sono guidati da una serie complessa di fattori tra cui prevalenza, trattamenti non ottimali e barriere che i pazienti devono affrontare nell’accedere alle risorse necessarie, incluso il supporto per la cura dei piedi. Una strategia integrata per il diabete è una soluzione che funzionerà per ridurre il carico di complicanze per le persone colpite dalla malattia. “

Blocco autore: Hussain MA, Al-Omran M, Salata K, Sivaswamy A, Forbes TL, Sattar N, Aljabri B, Kayssi A, Verma S, de Mestral C.

L’articolo “Tendenze secolari basate sulla popolazione nell’amputazione degli arti inferiori per diabete e malattia dell’arteria periferica” ​​è nel numero del 3 settembre 2019 di CMAJ .

Il CIEM è un istituto di ricerca indipendente e senza fini di lucro che utilizza informazioni sulla salute basate sulla popolazione per produrre conoscenze su una vasta gamma di questioni sanitarie. Le nostre prove imparziali forniscono misure delle prestazioni del sistema sanitario, una comprensione più chiara delle mutevoli esigenze di assistenza sanitaria degli ontari e uno stimolo per la discussione di soluzioni pratiche per ottimizzare le scarse risorse. La conoscenza del CIEM è molto apprezzata in Canada e all’estero ed è ampiamente utilizzata dal governo, dagli ospedali, dai pianificatori e dai professionisti per prendere decisioni in merito alla consegna delle cure e per sviluppare politiche. Nell’ottobre 2018, l’istituto precedentemente noto come Institute for Clinical Evaluative Sciences ha formalmente adottato l’inizialismo ICES come nome ufficiale. Per le ultime notizie su CIEM, seguici su Twitter: @ICESOntario

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Acute Skin Failure in the Critically Ill Adult Population

Skin failure (SF) is a term that first appeared in the literature in 1991. La Puma1 theorized that the skin, like all other organs, can fail. As a result of this physical decline and organ failure, pressure injuries (PIs) can occur.1 Since then, there have been multiple published definitions and variations on the term.2–8 However, ongoing debate surrounds the definition of SF and associated terms such as acute SF (ASF), chronic SF, and end-stage SF, as well as the clinical presentation of and diagnostic criteria for the condition.8

The failure of human organs, such as the heart, lungs, liver, and kidneys, is well defined; associated biomarkers guide treatment and prognosis.9–12 For patients in the ICU, evidence-based categorization instruments provide a numerical score to assess morbidity and illness severity and predict mortality. Such calculations are only achievable because objective measures of organ dysfunction are available. However, objective diagnostic markers and clinical parameters related to the integumentary system and SF are lacking;13 this limits the formulation of a globally agreed-upon diagnosis, classification, and definition for this phenomenon.

Varying definitions for SF have been presented in both the dermatology and skin integrity/wound care literature (Table 1). Although these definitions refer to a pathophysiologic process that affects the skin, the definitions are very different. The SF definitions from the dermatology literature have been used to describe SF that is attributable to trauma, such as thermal burns, autoimmune disorders, and severe infection.14 These definitions describe the etiology of SF as the result of a primary dermatologic condition with pathophysiologic changes resulting from integumentary inflammation and generalized loss of skin integrity.

Table 1
Table 1: 


In contrast, the skin integrity and wound care literature describes the etiology of SF as the result of a secondary pathophysiologic process that originates from failure of one or more organs other than the skin. As a result of organ failure elsewhere in the body, skin can be compromised and subsequently fail. Langemo and Brown’s5 2006 definition suggested SF is an “event in which the skin and underlying tissue die due to the hypoperfusion that occurs concurrent with severe dysfunction or failure of other organ systems.” In 2017, Levine8 built on this definition and proposed SF be defined as a “result of compromised tissue where the cells can no longer survive in zones of physiological impairment that includes hypoxia, local mechanical stresses, impaired delivery of nutrients, and build-up of toxic metabolic by-products.” Levine15 describes this definition as a way to consolidate and simplify differing nomenclatures into a universal diagnosis, proposing that SF is the underlying pathophysiology in wounds occurring in “patients close to death, unavoidable pressure injuries, and skin impairment related to tissue ischemia.” However, the association between SF and unavoidable skin changes remains unclear.

Pressure injuries are defined as “localized damage to the skin and underlying soft tissue usually over a bony prominence or related to a medical or other device. The injury occurs as a result of intense and/or prolonged pressure or pressure in combination with shear. The tolerance of soft tissue for pressure and shear may also be affected by microclimate, nutrition, perfusion, co-morbidities and conditions of the soft tissue.”16 More than 100 intrinsic and extrinsic risk factors for PI have been identified, including impaired mobility, diabetes, and skin status.17,18 It is plausible that a PI may develop in the presence of SF; however, skin damage occurring solely as a result of SF is not limited to areas of tissue loading alone. Therefore, PI development in the presence of SF is not certain, and SF may manifest in other ways; for example, gangrenous fingers or toes, blisters, or skin mottling.19,20

The multitude of interrelated terms and concepts used throughout the literature regarding SF, PI, unavoidable PI, terminal ulceration, and skin changes at the end of life has resulted in linguistic and conceptual confusion.19 Currently, three types of SF are described within the literature: acute, chronic, and end stage.5 Acute SF occurs concurrently with a critical illness such as septic shock.7 Chronic SF occurs in the presence of an ongoing chronic disease state such as dementia.21 End-stage SF occurs at the end of life. A Kennedy terminal ulcer (an event deeply embedded within the PI schema) is a manifestation of SF in patients at end of life.22 These definitions are subjective, based on clinical judgment, and lack objective criteria to determine categorization or the potential transition between categories (eg, moving from ASF to chronic SF or from chronic to end-stage SF).5 This has resulted in multiple terms being used interchangeably throughout contemporary literature. It is uncertain whether SF categories overlap or represent a continuum of acuity, although that issue is beyond the scope of this review. This problem does, however, highlight the need to clarify terminology through rigorous analysis of each concept, including similarities, differences, and interrelationships to improve clarity and ensure that concepts and terms have a solid theoretical and biologic basis.19

The primary aims of this systematic review were to assess and appraise the quality of studies conducted on ASF in adult patients in the ICU and identify evidence and gaps within the literature. The research questions were as follows:

  1. What is the definition of ASF in the adult intensive care population?
  2. What are the risk factors, causes, and antecedent conditions of ASF in the adult intensive care patient population?
  3. Is there an association between ASF and PI in the adult intensive care patient population?


Protocol Registration

This systematic review protocol has been registered in the International Prospective Register of Systematic reviews (PROSPERO): CRD42019126159.

Search Strategy

A preliminary literature search was undertaken using PubMed, MEDLINE (Medical Literature Analysis and Retrieval System), and CINAHL (Cumulative Index of Nursing and Allied Health Literature) to identify key terms and subject headings, with guidance from a specialized health sciences librarian. A systematic search for primary research was then undertaken in September 2018 using six databases: the Cochrane Library, Joanna Briggs Institute Evidence-Based Practice Database, CINAHL, Google Scholar, PubMed, and MEDLINE. The completed search strategy used for PubMed is detailed in Figure 1. The same keywords were used for all searches, and similar subject headings were used in the other five databases. Subject headings were explored where applicable. Limiters applied to the search were English language and dated from database inception to September 2018.

Figure 1
Figure 1: 


Inclusion and Exclusion Criteria

Qualitative or quantitative research studies that reported on ASF in critically ill adult human patients in the ICU setting were included.

Records were excluded if their study sample was animal or pediatric, if the study setting was not adult intensive care, and unrelated to SF. Studies were also excluded if they were written in a language other than English. Nonresearch publications, including conference papers, protocols, educational, opinion or commentary articles, other literature reviews, and guidelines, were excluded.

Study Selection

Abstracts were screened for eligibility and studies meeting the inclusion criteria were retrieved in full. The full-text publications were evaluated against the inclusion and exclusion criteria by two reviewers who worked independently and were blinded to each other’s assessments until selection was complete. Disagreements were resolved through discussion and consultations with third reviewers who acted as arbitrators where necessary.

Data Extraction and Synthesis

Data from the included records were extracted by one reviewer and summarized in data collection tables, which were checked and verified by the second reviewer.

Quantitative data synthesis was not attempted because of extensive heterogeneity attributable to the descriptive design of each study, lack of similar comparators, and lack of comparable data presented within the studies. Further, only one study23 used SF as a primary outcome; the other studies used PI development.7,24 A narrative synthesis approach was chosen to summarize the selected studies using the PICO (Population, Intervention, Comparator, and Outcome) framework.25 For each included record, study design, quality, population, intervention, comparator, outcome, and limitations were extracted. Each study also was assessed according to the National Health and Medical Research Council (NHMRC) evidence hierarchy.26 The results of the selected studies were tabulated to highlight important similarities and differences among studies (Table 2). The NHMRC evidence hierarchy was then used to define the recommendation grades: grade A is a body of evidence that can be trusted to guide practice; grade D is a body of evidence that is weak, from which recommendations should therefore be applied with caution.27

Table 2
Table 2: 


Quality Appraisal

The quality of the studies was assessed by two independent reviewers using the Mixed Methods Appraisal Tool (MMAT), version 2018 (Table 3).28 The MMAT is based on constructionist theory and has been used in more than 100 systematic mixed study reviews.29 It is designed for systematic reviews that include qualitative, quantitative, and mixed-methods studies. It was chosen for this review to ensure the different design methods could be reviewed using the same tool. The MMAT categorizes research using an algorithm of study selection criteria; each category is then appraised using two screening questions and five method quality questions based on the study design category.28 This enabled the authors to appraise the most common types of empirical studies concomitantly and effectively.29

Table 3
Table 3: 


The MMAT has separate categories for researchers to use depending on the type of research design to be assessed. Each category can be answered with yes, no, or cannot tell. The 2018 MMAT version discourages the calculation of an overall score. Using this method, each criterion can provide a more detailed presentation to better inform the quality of the included studies.28 There was only one MMAT question for one study for which assessors disagreed (Nowicki and colleagues’24 study had a clear research question), resulting in an overall interrater agreement of 95.24%. However, this disagreement was resolved through discussion.


The search returned 991 records. After duplicates were removed, 801 records remained. After titles and abstracts were screened against the inclusion and exclusion criteria, 779 records were excluded. Following the review of 22 articles retrieved for full-text evaluation, an additional 19 studies failed to meet the inclusion criteria; therefore, 3 articles were included in this review.7,26,24

These were categorized as quantitative nonrandomized7 and quantitative descriptive.23,24 The purpose of all three studies was to identify and describe factors that contributed to ASF and determine predictors of ASF in intensive care. Two of the studies were set in a single site (tertiary hospital centers).23,24 The third was a multicenter study involving a 55-bed ICU in a tertiary urban medical center and an 18-bed ICU in a suburban teaching hospital.7 Two studies employed a retrospective design,7,24 and the other used a prospective method.23 The NHMRC level of evidence for the three studies ranged between III-27 and IV,23,24 resulting in an overall D grade.27

No studies included in this review described a specific research question; rather, all presented an aim or research purpose. The data collected in two studies addressed the stated aims and purpose.7,24 However, it was unclear whether the data collected in the other study addressed the stated aim: to identify and describe the characteristics of ICU patients with SF.23 None of the studies were a “yes” for all MMAT criteria questions because of their potential risk of bias7,23,24 and a lack of clarity regarding the completeness of the data sets analyzed.7,24

Retrospective analysis using databases and patient notes increases the risk of bias attributable to systematic errors, inaccuracies, and the potential for missing data.30 This is evident in Nowiki et al,24 in which recorded data for more than 3 years (June 2006 to October 2009) were only partially available because of limited data recording (ie, incomplete outcome data were reported). Further, Delmore and colleagues’7 use of purposive sampling in the selection of patients with PI is prone to selection bias31 because the research intentionally selected certain patients with the outcome measure of interest (PI) and randomly selected patients without PIs. Further, little information regarding the amount or nature of missing data was described within these two studies.7,24 Curry and colleagues’23 study is at risk of bias because the authors did not state the criteria used by the certified wound care nurses to diagnose ASF prospectively. This places the study at risk of research bias. It also may impact the validity of data collected in answering the research question.23


The studies included 1,307 intensive care participants, with 29 participants in the prospective study23 and the remaining 1,278 participants in the retrospective studies.7,24 Two studies were based in the US7,23 and one study in Australia.24 One study did not report the participants’ sex, age, or race.24 The other two included 328 males and 253 females, resulting in a 1.3:1 male-to-female ratio; this is representative of the ICU patient population, 60% of whom are male.7,23,32 The age of participants in these two studies ranged from 19 to 99 years (mean, 71 [SD, 15.7] years7 and 58.82 [SD, 15.29] years,23 respectively). The majority of study participants were white (n = 457, 78%).7,23 Other ethnic backgrounds represented were as follows: black/African American (n = 45, 8%), Hispanic (n = 47, 8%), Asian/Pacific Islander (n = 31, 5%), and other (n = 1, 0.2%), resulting in a rounded ratio of 4:1 white to cumulative minority groups.7,23


Study authors defined ASF using the Langemo and Brown5 definition in two of the three studies.7,23 The third study provided no ASF definition; rather, the authors describe SF occurring as a result of hypoperfusion and secondary to the underlying patient condition and use of vasoactive drugs, causing poor tissue tolerance and leading to PI formation.24 This study was included in the analysis because it met the inclusion criteria. Further, this distinction in terms demonstrates the linguistic and conceptual confusion currently surrounding this phenomenon.

In two retrospective studies, PI development was the primary outcome measure.7,24 The third study used a certified wound and ostomy care nurse to assess ASF prospectively,23 although again the diagnostic criteria were not described. As a result, the lack of diagnostic criteria may contribute to researcher bias and potentially influence reliability and consistency.


Comparator groups were used in both retrospective studies.7,24 One study compared PI rates in ICU patients with non-ICU patients and confirmed an increase in PI development over time in the ICU group (from 4.6% [71/1,532] PI incidence in 2006 to 7.5% [128/1,699] in 2015).24 The other study compared the physiologic characteristics of ICU patients who developed PIs with a control group of ICU patients who did not develop PIs.7 This comparison enabled a logistic regression analysis that showed independent predictors of ASF.7


Risk factors for ASF were determined by one study’s use of logistic regression analysis and reported statistically significant and independent predictors of ASF.7 This study found the predictive variables for ASF were: peripheral arterial disease (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.64–8.66), mechanical ventilation longer than 72 hours (OR, 3; 95% CI, 1.78–5.05), respiratory failure (OR, 3.2; 95% CI, 1.82–5.40), liver failure (OR, 2.9; 95% CI, 1.05–8.08), and severe sepsis/septic shock (OR, 1.9; 95% CI, 1.14–3.20). Another study found more than 90% of their cohort diagnosed with ASF had the following antecedent conditions: renal failure, respiratory failure, more than one organ system (other than skin) failing, and albumin levels less than 3.5 mg/dL.23

The final study found an increase in ICU PI incidence from 4.6% (71/1,532) of ICU episodes of care to 7.5% (128/1,699) of ICU episodes of care over a 9-year period (2006–2015).24 This study also reviewed the clinical characteristics of a subset of 13 ICU patients with severe PIs (Stages 3 and 4)24 and found 30% (4/13) of this cohort had an admission diagnosis of septic shock; 38% (5/13) required extracorporeal membrane oxygenation therapy; 69% (9/13) required renal replacement therapy; and 100% (13/13) were treated with more than two vasopressors or inotropic pharmacologic agents. The authors hypothesized that the clinical characteristics of this subset of ICU patients may be more appropriately attributed to antecedents of SF rather than the predictors of PIs.24

Each study had several limitations. Single-site studies, although important, have limited generalizability.23,24 One study’s small sample size,23 as well as the lack of documented ASF diagnostic criteria identified in any of the studies, impacted the generalizability of these findings.7,23,24 A confounding bias for two studies was the use of PI development as a surrogate marker for ASF.7,24 Given the lack of evidence substantiating a pathophysiologic link between ASF and PI, it cannot be confirmed that the findings from these studies are specific to ASF alone.

Two studies lack generalizability because of the use of unique subspecialties such as elective cardiothoracic surgical patients.7,24 These patients are often stable prior to surgery and critically ill for only a short period.7 The lack of generalizability was also evident in the cohort mix, with a disproportionate ratio of whites to other ethnicities (4:1) represented within the collective studies.7,23

The two retrospective studies, despite having the largest cohorts,7,24 have limited generalizability because of their retrospective design. Further, one study had a 9-year timeline (2006–2015), resulting in data collection over a period in which differing classification systems were used to categorize PI stages.24 These limitations may have also been compounded with the use of multiple reporting systems to collect these data.24


The few studies eligible for inclusion in this review illustrate that research is limited regarding ASF in the adult intensive care patient population. This includes the apparent lack of consensus and evidence to define ASF in this cohort; limited understanding of risk factors, causes, and antecedent conditions for ASF; and scant evidence supporting PI etiology and development because of ASF.

Globally, ASF has no agreed-upon definition, and related research remains inconsistent as a result. The definition of ASF, although previously described within dermatologic literature, was redefined by Langemo and Brown within the wound care literature, citing an alternative etiology for the condition (hypoperfusion in the context of patient acuity).5 As a result, the definition of ASF not only lacks consensus within the wound care community, but it also has different meanings depending on whether it is used in the wound care or dermatology context.

Significant conceptual confusion surrounding ASF remains. This is most evident in the retrospective studies included in this review,7,24 in which ASF may have been erroneously labeled as PI. However, ASF does not require factors necessary for PI development such as mechanical stress. Acute SF can occur on the body in areas of no mechanical stress, manifesting, for example, as necrotic digits.14 Further, when the label ASF is applied retrospectively to only those patients who developed PIs, patients who may have developed ASF without PI development are missed. Whether this is right or wrong, this is the current point at which researchers and clinicians find themselves.

This systematic review illustrates a paucity of research available on ASF in the intensive care patient population and the need for rigorous analysis regarding the etiology and pathophysiology of ASF including similarities, differences, and interrelationships to other skin changes. This will ensure a solid theoretical and biologic foundation for defining the term and lead to practice improvement and global patient benefit.


This review has some limitations. First, the search strategy was limited to original research written in English; gray literature was excluded. Gray literature consists of a wide range of formats and scopes that can often be a rich source of evidence, although it is usually not subject to peer review.33 Second, the small number and heterogeneity of studies found on this topic prevented a true meta-analysis.


This systematic review aimed to present the current evidence regarding ASF by reviewing the risk factors, causes, and antecedent conditions; identifying associations between ASF and PI development; and understanding the definition of ASF in the adult ICU population.

The results of this systematic review highlight a substantial evidence gap in this area. Further research regarding etiology, diagnostic biomarkers, and predictors of SF is warranted to assist in formulating an accurate and agreed-upon definition, as well as improving skin integrity outcomes in patients who are critically ill.

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Tentativo di recupero degli arti in un paziente con ischemia critica degli arti e comorbilità multiple

Ci sono altre opzioni da considerare quando più fornitori hanno consigliato l’amputazione sotto il ginocchio per un paziente? Con un caso di studio intrigante, questo autore illustra come un approccio concertato e multidisciplinare può ancora portare al recupero degli arti nonostante complicazioni e problemi con la non aderenza del paziente. 

Un maschio caucasico di 64 anni con una storia di ischemia critica degli arti è stato presentato per la prima volta nell’aprile 2017. Aveva una storia medica passata di malattia coronarica, ipertensione, broncopneumopatia cronica ostruttiva (BPCO), malattie renali e uso quotidiano di tabacco. Il paziente ha avuto un infarto miocardico nel 2009 e nel 2015 gli è stato diagnosticato un aneurisma dell’aorta addominale (AAA). 

Qualche mese prima di presentarmi nel mio ufficio, la paziente ha subito una dissezione aortica, che ha portato a ischemia critica degli arti. Entro un mese dalla riparazione della dissezione aortica, il paziente aveva un bypass carotideo. Poco dopo, ha sofferto di complicazioni da un precedente stenting renale, che ha provocato insufficienza renale e inizio dell’emodialisi. 

Circa un mese dopo la dissezione aortica e mentre il paziente era ancora ricoverato in ospedale, ebbe un evento di tempesta trombotica e notò segni di lesioni ischemiche e manifestazioni dermatologiche di trombosi, insieme a scolorimento delle cifre del piede sinistro. Per un periodo di tre settimane, sviluppò gradualmente la cianosi e la cancrena successiva all’aspetto distale del piede coinvolto. Il paziente ha consultato quattro medici che tutti hanno raccomandato un’amputazione al di sotto del ginocchio (BKA) della gamba sinistra. Ho accettato un rinvio per fornire un’opinione aggiuntiva per questo paziente. 

Il paziente aveva una frazione di eiezione del 40 percento ed era ancora in emodialisi. All’esame, era evidente che il paziente aveva ridotto gli impulsi del pedale. C’era cancrena secca sul piede sinistro con una linea di demarcazione da dorsale a plantare (vedi foto in alto sopra). La cancrena si estendeva più prossimamente plantare che dorsalmente e circonferenzialmente dal mesopiede alle cifre con necrosi e essiccazione. Alla linea di demarcazione, c’era una base ferita sottocutanea fibrosa con transizione prossimale alla pelle normale. 

Le culture hanno rivelato la Finegoldia magna (un anaerobo) e lo Staphylococcus aureus , portando all’inizio della doxiciclina e del metronidazolo. Il debridement del tessuto sottocutaneo ha rivelato il tessuto sanguinante sottostante, che indicava un certo livello di potenziale di guarigione. Il chirurgo vascolare ha indicato che il paziente presentava la vascolarizzazione massima con impulsi di pedale ottimali e adeguata perfusione alla caviglia sinistra. Sentiva anche che c’era un flusso di sangue sufficiente verso la parte centrale del piede per curare eventualmente un’amputazione transmetatarsale (TMA). Ho informato il paziente dell’importanza della cessazione del fumo e dell’opzione dell’ossigenoterapia iperbarica (HBOT). Dopo aver valutato il suo caso, ho sentito che le opzioni chirurgiche differenziali includevano un TMA prossimale rispetto a un’amputazione di Chopart rispetto a un BKA. 

Pianificazione di un approccio multidisciplinare e graduale al recupero degli arti

Nella prima fase del piano chirurgico, abbiamo sbrigliato il sito di demarcazione tra la cancrena e il tessuto sano e applicato un sostituto dell’innesto cutaneo. Gli obiettivi di questo approccio iniziale erano consentire una maggiore guarigione della pelle e preparare un lembo adeguato per un TMA. Il paziente ha iniziato HBOT. Due settimane dopo questo primo intervento, il paziente ha sviluppato pancreatite acuta, con conseguente ricovero di una settimana e interruzione dell’HBOT. Durante il ricovero in ospedale, ci fu una consultazione in merito alla corretta alimentazione per la guarigione delle ferite. L’area di applicazione dell’innesto ha mostrato nuova crescita di tessuto e progressione della ferita. 

Un mese dopo la prima procedura, ho eseguito un TMA prossimale a livello delle basi metatarsali. Ho utilizzato un lembo da dorsale a plantare anziché da plantare a dorsale a causa del livello prossimale della cancrena del piede plantare, ma c’era un deficit persistente del tessuto nel moncone distale. Per completare questa copertura, ho applicato un innesto cutaneo a spessore diviso, che è stato raccolto dalla coscia sinistra del paziente.

Il paziente non ha aderito alle istruzioni non pesanti dopo l’intervento. L’innesto cutaneo a spessore parziale non è riuscito e ho consigliato di riprendere l’HBOT per un lembo non riuscito. Ha continuato a fumare e non è stato coerente nel mantenere gli appuntamenti HBOT postoperatori. Durante questo periodo, ha sofferto di nausea e episodi di vomito a causa di pancreatite acuta insieme a sensibilità e dolore al sito chirurgico. Il sito del donatore sulla coscia sinistra è guarito entro due settimane. Ha ricevuto cure locali per le ferite nel sito ricevente del trapianto distale. Ho rimosso le suture a tre settimane e successivamente il paziente ha iniziato a perdere peso parzialmente (solo con il tacco) una settimana dopo in uno stivale pneumatico con deambulatore.

A cinque settimane dall’intervento il paziente presentava un dolore minimo, l’incisione si chiudeva e il paziente continuava a deambulare con il deambulatore con il deambulatore. A nove settimane, il paziente è stato completamente guarito. A 12 settimane, è passato a scarpe su misura con stucchi e pieno peso. Un mese dopo, ha dimostrato il cambio di marcia adeguato sulla sua moto. Sei mesi dopo il suo intervento iniziale, è tornato alla sua solita base di attività completa. 

Pensieri finali

Questo è un caso estremo di recupero degli arti e cura delle ferite a lungo termine. L’esito positivo di questo caso è derivato da un approccio multispeciale che comprende vascolare, cardiologia, malattie infettive, medicina interna, nefrologia e podologia. Inoltre, l’innovazione sulla consueta costruzione del lembo TMA, l’aggiunta dell’HBOT e l’attenzione aggressiva alle complicazioni nella fase iniziale hanno contribuito al risultato in questo caso complesso. 

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Novel Bacterial Auto-fluorescence Imaging Device Can Lead to More Targeted Debridement

Acute wounds heal by progressing through a complex, but orderly, series of physiologic and molecular processes. In contrast, chronic wounds, those that fail to heal within 30 days, are characterized as having stalled in this healing progression due to a variety of systemic and local factors. Such factors include high microbial burden and excessive devitalized tissue.1 Within 48 hours of development, Gram positive bacteria from the environment or the patient’s skin flora can infiltrate an open wound2,3; wound healing becomes potentially compromised once bacteria have invaded.

A crucial component of wound management is regular debridement.4 The goal of debridement is to remove all necrotic, fibrous, and devitalized tissue from the wound bed, control infection, and establish a balanced healing environment.4,5 Devitalized tissue in wounds produces a physical barrier to the formation of new tissue and therefore decreases healing rates. If devitalized tissue remains in the wound bed, there is an increase in concealed dead spaces, which can make bacterial colonization in and around the wound more likely. Standard of care remains that unhealthy tissue be sharply debrided to bleeding tissue to: (1) allow for visualization of the extent of the ulcer; (2) detect underlying exposed structures, deep bacterial contamination, or abscesses; and (3) assess the quality of the periwound tissue. Frequent and thorough debridement reduces bacterial bioburden.5 In some cases, although the debridement adequately removes devitalized tissue, the remaining wound bacteria may become problematic.

Bioburden is an all-encompassing term that includes necrotic material, nonviable tissue, wound exudate, and bacteria and other microbes (e.g., fungi). Bioburden tends to accumulate continually in chronic wounds as a result of the underlying pathogenic abnormality caused by systemic conditions such as diabetes or venous disease. The inability to fully resolve these fundamental physiologic issues makes chronic wound bed management with aggressive and complete debridement even more crucial. A point-of-care auto-fluorescence imaging system to aid in bacterial-targeted debridement and bioburden management in the treatment of chronic wounds could prove to be an extremely useful tool to improve patient outcomes.

A novel advancement in wound imaging called the MolecuLight i:X (manufactured by MolecuLight, Inc., Toronto, Ontario, Canada) is now available. This handheld device is an easy-to-use, noninvasive, portable point-of-care fluorescence (Fl) imaging device (Figure 1). The MolecuLight i:X instantly visualizes potentially harmful bacteria on the wound surface and surrounding tissues not otherwise visible with the naked eye. The device emits a violet light (405 nm) that illuminates the wound and surrounding area, exciting the wound tissues and bacteria and resulting in endogenous production of Fl signals3 without the need for additional contrast agents.6 Optical filters built into the device remove noninformative colors, without any digital processing, and one can view the resulting image on the display touch screen in real time.7

The Fl signals (i.e., colors) produced are tissue specific6; endogenous tissue components such as collagen will fluoresce green, while clinically relevant bacteria producing metabolic byproducts like porphyrins and pyoverdine fluoresce red and cyan (blue-green), respectively.8,9 The MolecuLight i:X has been extensively validated in preclinical10 and clinical studies involving patients with chronic wounds.11-15 Clinical trials have shown that endogenous red fluorescent porphyrins emitted from bacteria allow the visualization and location of bacteria present at loads ≥ 104 CFU/g.12

The device has been noted to detect these fluorescent bacterial byproducts on and beneath the surface of wounds, up to ~1.5 mm depth.12 It should be noted that numerous porphyrin-producing bacterial species can colonize on chronic wounds and cause a red fluorescence, but Staphylococcus aureus is the most commonly found bacterial species.11,16 Pyoverdine is unique to Pseudomonas aeruginosa; thus, it is the only bacteria to fluoresce cyan.7,17 The information captured in the images can aid in improved decision making throughout the dynamic wound treatment pathway (e.g., pre-debridement, post-debridement), and in determining the need for antimicrobial therapy.13

The device also contains wound area measurement software that automatically detects the wound border and generates instant, precise wound measurements (wound surface area, length and width). Operators place 2 yellow wound measurement calibration stickers (Figures 2A, 3A, 4A, 5A) in the plane of the wound, 1 on either side, and within the camera’s field of view. A photograph is then taken in the device’s standard imaging mode. By engaging the measure button on the touch-screen, the border is automatically detected and measurements of wound length, width and surface area are displayed on the screen. If preferred, the clinician has the option of using a stylus to outline the wound border manually for measurement.

This case series of 10 patients reports the use of the device’s Fl and wound measurement capabilities to assess wounds and to aid in bacterial-targeted debridement and bacterial burden management in treatment of chronic wounds of the lower extremity.


This case series was observational in nature and no specific inclusion/exclusion criteria were applied to the patients; however, all patients evaluated had an open wound of the lower extremity with a range of chronic wound etiologies, and were > 18 years of age. Patients signed a photo-release consent and were not compensated for participation.

Fluorescence images should always be acquired in a dark environment. A sensor on the device indicated when sufficient darkness for optimal Fl detection was obtained. A rangefinder indicator on the device was used to indicate when the device was at the ideal distance for imaging (8 cm to 12 cm from the wound). The device was used at each patient’s weekly visit to collect wound measurements, standard images, and Fl images to assess wound healing and bacterial burden. Images positive for bacterial Fl (regions of red or cyan) were used to guide debridement to those specific wound regions. Debridement was performed as per standard of care using surgical blade or curette. Data was analyzed to determine the usefulness of the innovative imaging system in ascertaining the effectiveness of debridement, directing the clinical treatment course and influencing the rates of healing in each wound.


Ten patients (5 women, 5 men) were included in this analysis. Wounds had varying etiologies: 4 traumatic wounds, 3 venous leg ulcers, 2 diabetic foot ulcers, and 1 surgical wound. The median patient age was 74.9 years (range, 60-99 years). Wounds were located on the right lower leg (4), the left lower leg (3), the left heel (1), the right heel (1), and the left distal foot/post-transmetatarsal amputation (1). Upon initial presentation to the clinic, the mean ulcer duration was 16.5 weeks (range, 4-32 weeks) with a mean ulcer area of 8.3 cm2 (range, 1.1-35.0 cm2). Using an adaptation of the Wound Infection in Clinical Practice checklist (Table 1),18 all wounds were evaluated as clinically uninfected at the initial assessment visit. All study wounds were considered to display delayed wound healing beyond clinical expectation, but no wounds demonstrated signs of spreading infection. The deepest exposed tissue layer noted on initial presentation was partial thickness (1), subcutaneous (SubQ; 8), and fascia/tendon (1). Most patients had only 1 Fl-directed debridement performed at each visit; a second Fl-guided debridement during a visit was performed on patient 2 at visit 2, patient 4 at visit 2, and patient 6 at visit 1 to remove additional devitalized tissue and red fluorescing material noted within the wound bed.

Case 1

Patient 1 was a 67-year-old woman with a history of trauma to the left lower leg from an automobile accident. The wound duration was 16 weeks at the time of the initial visit. Upon clinical evaluation, there appeared to be no evidence of bacterial contamination or infection. Wound measurement was 1.63 cm2. At visit 1, the wound was noted to have a positive fluorescent signal (Fl+) both in the wound and around the periwound area (Figure 2A, 2B). Debridement did not noticeably change the fluorescent signal at this visit (Figure 2C, 2D). She was treated daily at home with an enzymatic debriding agent and a hydrophobic, bacterial-binding, nonadherent contact layer. The patient was seen weekly in the clinic for evaluation and underwent wound debridement to the SubQ level. At visit 3, it was noted that the wound had a negative fluorescent signature (Fl-) and very scant Fl in the periwound skin (Figure 2E, 2F) and wound size had decreased to 1.16 cm2. However, on visit 5, the periwound area exhibited an alarming red Fl+ signature and the wound measurement increased to 1.40 cm2 (Figure 2G, 2H). This was thought to be early signs of cellulitis, and the patient was placed on doxycycline hyclate (100 mg twice/day for 10 days). At visit 6, the wound size was noted to have decreased to 1.30 cm2 and the fluorescent signal seen previously in the periwound area had resolved (Figure 2I, 2J). It is the author’s opinion that the MolecuLight i:X was able to pick up early cellulitis otherwise not appreciable with the naked eye, allowing for early antibiotic therapy to prevent advancing clinical symptoms and possible need for hospitalization.

Case 2 

Patient 2, a 63-year-old man, presented with a trauma wound to his right lower leg after falling off a ladder. The duration of the wound at presentation was 13 weeks with measurements of 5.10 cm2 and 0.7 cm depth. Clinically, the wound was noted to have a moderate amount of devitalized tissue present, but it did not appear to be overtly infected (Figure 3A). The Fl image showed evidence of red and cyan Fl in and around the wound (Figure 3B). The post-debridement Fl image showed a decrease in cyan Fl but an increase in red (Figure 3C, 3D). He was treated daily at home with an enzymatic debriding agent and a hydrophobic, bacterial-binding, nonadherent contact layer. The patient was seen weekly in the clinic for evaluation and underwent wound debridement to the SubQ level. By visit 5, it is noted that the wound exhibited a marked decrease in red and cyan Fl in the pre-debridement image; the wound size measured 3.77 cm2, and the wound character improved with a decrease in depth to 0.3 cm (Figure 3E, 3F). At visit 5 post-debridement, the wound was Fl- (Figure 3G, 3H).

Case 3

Patient 4 was a 60-year-old woman who presented with a trauma wound of the right lower leg of 28 weeks’ duration. Upon initial presentation, it was noted that the wound (4.76 cm2) had a significant amount of devitalized tissue present without evidence of acute bacterial contamination (Figure 4A). Pre-debridement imaging showed red Fl in and around the wound (Figure 4B). Post-debridement images showed a decrease in the red Fl within the wound, though it still observable red Fl in the periwound area (Figure 4C, 4D). The patient was treated daily at home with an enzymatic debriding agent and a hydrophobic, bacterial-binding, nonadherent contact layer. She was seen weekly in clinic for evaluation and underwent wound debridement to the level of exposed tendon. By visit 3, the wound had decreased in size to 2.21 cm2 and there was decreased evidence of bacterial Fl in the wound and minimal signal seen in the periwound area on the post-debridement Fl image (Figure 4E, 4F). After this visit, the patient was lost to follow-up due to admission into a nursing facility.

Case 4

Patient 6, a 71-year-old woman, presented with a 14-week history of a DFU of the right heel. Upon initial evaluation, the wound measured 1.14 cm2 and was free of acute signs of bacterial infection (Figure 5A). Initial Fl images showed evidence of red and cyan Fl pre-debridement (Figure 5B), with remaining red Fl in the periwound area post-debridement (Figure 5C, 5D). She was treated with a polyhexamethylene biguanide hydrochloride collagen matrix in the clinic and seen for weekly wound evaluation and SubQ tissue debridement. By visit 4, the wound measurement was 0.15 cm2 (Figure 5E, 5F). Following debridement at this visit, the wound was completely Fl- and the periwound area showed very slight Fl+ (Figure 5G, 5H).


Fluorescence imaging with the MolecuLight i:X is an innovative new addition to the field of wound care. The technology allows providers to obtain real-time detection of Fl from bacteria at loads of ≥ 104 CFU/g.11 Clinical studies have consistently shown that the red and cyan signals seen on the MolecuLight i:X images are predictive of moderate to heavy bacterial loads.13,15 It is the authors’ observation that Fl+ found within the wound decreased with debridement at each visit and over the course of therapy. Fl+ found in the periwound area did not, however, decrease significantly with debridement alone; a secondary antimicrobial dressing or oral antibiotics were used to treat patients in these instances. In the cases examined, it was noted that Fl- images correlated to an overall decrease in wound size over the course of treatment. Integration of Fl imaging also enabled bacterial burden-targeted decision making on tissues to remove during debridement. Furthermore, Fl image analysis allowed for bacterial burden-based decision making regarding wound dressings and therapies. Therapies were selected to treat the wound as well as the periwound area.


Current debridement practices have little effect on the periwound tissue and the bioburden found in this region. Routine clinical observations are unable to detect bacterial load and bioburden in the absence of acute bacterial infection and provide no information on bacterial location. Standard clinical practice may not be sufficient to remove bacterial burden and may leave unacceptable levels of bacteria behind (≥ 104 CFU/g). The goal of wound debridement is to facilitate wound healing. This case series noted, over time, with weekly debridement and Fl-directed therapies, bacterial loads decreased within the wound base and the periwound tissues throughout the course of therapy.

There is potential to improve patient outcomes by incorporating Fl imaging into current clinical pathways. By practicing Fl-guided debridement, regions of bacterial burden can be targeted, helping clinicians determine how much and where to selectively remove tissue. As case 1 demonstrated, Fl imaging can potentially identify very early cellulitis before clinical evidence is noted. Early identification and determination of appropriate therapy via Fl imaging may prevent acute cellulitis, abscess, hospitalization, and/or surgical intervention, thus saving health care dollars. In the future, Fl imaging of chronic wounds may usher in a paradigm shift in the wound care community in which more careful attention is paid to the periwound area and treatments are not directed solely to the wound base.

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Infiammazione ma non come la conosci tu!

Parliamo molto dell’infiammazione della ferita e molti di voi saranno consapevoli del processo cellulare coinvolto nell’infiammazione cronica della ferita. Le metalloproteinasi della Matrice sollevate (MMP) e le citochine all’interno della ferita sono spesso viste come i colpevoli del perché le ferite non riescono a guarire.

Tuttavia, sei consapevole che l’ipertensione venosa aumenta questi stessi enzimi all’interno dei tessuti, sia che tu abbia una ferita o no?

Alla conferenza del Center of Interdisciplinary Research on Compression (CIRC) dell’ottobre 2019, Leanne Atkin e Alison Hopkins hanno avuto il piacere di ascoltare ricercatori ed esperti chiave in questo campo. Tutte le presentazioni hanno indicato la potente risposta all’infiammazione della gamba e dei tessuti in risposta all’ipertensione venosa gravitazionale.

Molti dei sintomi segnalati dai pazienti sono legati esclusivamente alla risposta infiammatoria: eczema, edema, lipodermatosclerosi, prurito, dolore e pesantezza. Questi sono tutti dovuti all’attivazione di un numero di marker infiammatori, inclusi MMP e citochine, proprio come in una ferita.

Quindi è eccitante sentire che la compressione ha un ruolo importante nel ridurre questi mediatori dell’infiammazione. È stato dimostrato che la terapia compressiva riduce MMP e citochine offrendo un’elevata azione antinfiammatoria. Quindi dimentica i farmaci antinfiammatori non steroidei: pensa invece a quale dose di compressione devi somministrare per creare un effetto antinfiammatorio.

La compressione del dosaggio deve essere personalizzata; dobbiamo allontanarci dal magico 40 mmHg, poiché per molti pazienti questa potrebbe non essere una dose abbastanza forte di trattamento antinfiammatorio.

Quindi è stato favoloso ascoltare gli esperti del CIRC che descrivono come questa risposta infiammatoria possa essere “disattivata” con una compressione efficace. Ma la realtà è che nel Regno Unito abbiamo un uso crescente di compressione subottimale o nulla. Ci rendiamo conto che la nostra pratica quotidiana è molto lontana da questa scienza emergente. Come possiamo colmare questa lacuna? Come possiamo mettere in cascata queste conoscenze e tradurle in benefici per i nostri pazienti e personale?

Dobbiamo cambiare la narrativa dal parlare di una ferita bloccata nello stadio infiammatorio a quella dell’arto bloccato anche lì? Ciò renderebbe più chiara la necessità di compressione per voi e i vostri pazienti?

Il compito per noi è garantire che tutti riconosciamo i cambiamenti della pelle venosa e l’edema come parte del processo infiammatorio. Siamo fortunati che a differenza di molte altre condizioni infiammatorie come l’artrite e il cancro, lo stimolo distruttivo può essere attivato e disattivato semplicemente in piedi / mentendo o mitigandolo con la dose appropriata di terapia compressiva. Quindi “spegnere l’infiammazione delle gambe” è un concetto di cui abbiamo bisogno per mettere le nostre teste e parole in giro; porta una forte enfasi sul ruolo della compressione come terapia, l’arte e l’applicazione tecnica da parte del medico e la dose individuale richiesta per i nostri pazienti.

La sfida per tutti noi è:

  • Riconosci che lo stato infiammatorio dell’arto deve essere attivamente ridotto
  • Titolare appropriatamente la dose di compressione per garantire una risposta antinfiammatoria
  • Comprendi che la terapia compressiva è una potente terapia potente, comprovata ed efficace

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