Cathelicidin ΔPb-CATH4 derived from Python bivittatus accelerates the healing of Staphylococcus aureus-infected wounds in mice.

The effects of ΔPb-CATH4, a cathelicidin derived from Python bivittatus, were evaluated against Staphylococcus aureus-infected wounds in mice. These effects were comparable to those of classical antibiotics. ΔPb-CATH4 was resistant to bacterial protease but not to porcine trypsin. A reduction in the level of inflammatory cytokines and an increase in the migration of immune cells was observed in vitro. Thus, ΔPb-CATH4 can promote wound healing by controlling infections including those caused by multidrug-resistant bacteria via its immunomodulatory effects.

A Comprehensive Review of the Pathogenesis, Diagnosis, and Management of Diabetic Foot Infections.

GENERAL PURPOSE: To review an approach to diabetic foot infections (DFIs), including acute osteomyelitis, while also discussing current practices and the challenges in diagnosis and management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will1. Identify the risk factors for developing DFIs.2. Outline diagnostic techniques for assessing DFIs.3. Select the assessment techniques that support a diagnosis of osteomyelitis.4. Choose the appropriate pharmacologic and nonpharmacologic treatment options for patients who have DFIs. ABSTRACT: Diabetic foot ulcers result from a combination of peripheral neuropathy, vascular compromise, and repetitive trauma. Approximately 50% of individuals with diabetic foot ulcers will develop a diabetic foot infection (DFI), and 20% of individuals with a DFI will develop osteomyelitis. Herein, the authors review an approach to DFIs including acute osteomyelitis and discuss current practices and challenges in diagnosis and management.The diagnosis of a skin and soft tissue DFI is based on clinical criteria. A bone biopsy is considered the criterion standard for diagnosis of osteomyelitis; however, biopsy is not always feasible or available. Consequently, diagnosis can be made using a combination of clinical, biochemical, and radiographic findings. X-ray is the recommended imaging modality for initial evaluation; however, because of its lower relative sensitivity, advanced imaging may be used when clinical suspicion remains after negative initial testing.The microbiology of skin and soft tissue DFIs and osteomyelitis is similar. Staphylococcus aureus and other Gram-positive cocci are the most common pathogens identified. Deep cultures are preferred in both DFI and osteomyelitis to identify the etiologic pathogens implicated for targeted antimicrobial therapy. Management also requires a multidisciplinary approach. Surgical debridement in those with deep or severe infections is necessary, and surgical resection of infected bone is curative in cases of osteomyelitis. Finally, appropriate wound care is critical, and management of predisposing factors, such as peripheral neuropathy, peripheral arterial disease, tinea, and edema, aids in recovery and prevention.

Functional ambulatory status as a potential adjunctive decision-making tool following wound, level of ischemia, and severity of foot infection assessment.

The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System has been developed to stratify amputation risk on the basis of extent of the wound, level of ischemia, and severity of foot infection (WIfI). However, there are no currently validated metrics to assess, grade, and consider functional status, especially ambulatory status, as a major consideration during limb salvage efforts. Therefore, we propose an adjunct to the current WIfI system to include the patient's ambulatory functional status after initial assessment of limb threat. We propose a functional ambulatory score divided into grade 0, ambulation outside the home with or without an assistive device; grade 1, ambulation within the home with or without an assistive device; grade 2, minimal ambulation, limbs used for transfers; and grade 3, a person who is bed-bound. Adding ambulatory function as a supplementary assessment tool can guide clinical decision making to achieve optimal future functional ambulatory outcome, a patient-centered goal as critical as limb preservation. This adjunct may aid limb preservation teams in rapid, effective communication and clinical decision making after initial WIfI assessment. It may also improve efforts toward patient-centered care and functional ambulatory outcome as a primary objective. We suggest a score of functional ambulatory status should be included in future trials of patients with chronic limb-threatening ischemia.

25-Hydroxyvitamin D Deficiency: Impacting Deep-Wound Infection and Poor Healing Outcomes in Patients With Diabetes.

BACKGROUND: The Kingdom of Bahrain has a high incidence of diabetes and associated foot complications. Simultaneously, low 25-hydroxyvitamin D (25[OH]D) levels are common in this population and may be associated with the traditional clothing used in desert climates. METHODS: This investigation compared 25(OH)D levels and glycemic control with quantifiable wound healing parameters in a prospective, analytic, nonexperimental, cross-sectional pilot study. Consecutive consenting adult patients (N = 80) who presented to the regional wound care unit in January 2016 with either an existing or new wound were included. Collected data included three-dimensional wound photography, NERDS and STONEES criteria, and an X-ray with a positive probe-to-bone test. Blood values for 25(OH)D and hemoglobin A1c (HbA1c) were collected simultaneously. RESULTS: Diabetes mellitus (types 1 and 2) was present in 90% of the sample patients. No patient had sufficient 25(OH)D levels; 15% had insufficient levels (30-50 ng/mL), and deficiency (levels <#20 ng/mL) was found in 85% of the sample. Males were slightly less affected by 25(OH)D deficiency compared with females (82.4% vs 91.3%). Poor glycemic control (HbA1c levels >#6.8%) was found in 69.4% (n = 50) of the persons with diabetes included in the sample. Those with both diabetes mellitus and a 25(OH)D deficiency (76.3%; n = 61) were more likely to demonstrate healing difficulty (40.9%; n = 25) or present with a stalled or deteriorating wound (44.2%, n = 27). A 3° F or higher periwound surface temperature elevation over a mirror image site was present in 82.5% of all wounds. Exposed bone in the ulcer base was found in 50% of the cases. For persons with diabetes, general linear modeling statistical analysis (adjusted R value = 47.9%) linked poor wound healing with three studied variables: 25(OH)D deficiency, poor glycemic control, and an exposed bone in the wound bed. CONCLUSIONS: Vitamin D may be an overlooked factor in the pathophysiology of diabetic foot ulcer development and subsequent delay in wound healing outcomes. The authors recommend adding 25(OH)D deficiency to the list of multifactorial aggravating factors providers should consider correcting in this subgroup of patients.

A review of interventions to reduce pain in chronic wounds.

Reduction of chronic wound pain has the potential to improve patients' quality of life, expedite the healing process and, ultimately, relieve pressure on community services. Despite this, education on pain assessment in the management of chronic wounds is lacking. This literature review seeks to provide evidence-based recommendations to reduce chronic wound pain and inform the practice of community nurses. The results of a thematic analysis indicate that a honey dressing or native collagen matrix dressing and conditioning exercises for the lower leg can reduce pain, and nitroglycerin ointment is especially effective. The review also highlights the need for an individualised approach to the assessment and treatment of pain in patients with chronic wounds.

The impact of foot infection on infrainguinal bypass outcomes in patients with chronic limb-threatening ischemia.

BACKGROUND: Despite advances in endovascular therapy, infrainguinal bypass continues to play a major role in achieving limb salvage. In this study, we sought to compare outcomes of infrainguinal bypass in patients with limb-threatening ischemia who presented with or without foot infection. METHODS: We conducted a retrospective cohort study of patients who underwent infrainguinal bypass for chronic limb-threatening ischemia at a single institution. End points of interest included long-term mortality, 45-day readmission, postoperative length of stay (LOS), major amputation, and time to wound healing. Multivariable Cox, logistic, and robust regressions were used to model time to event outcomes, readmission rates, and LOS. RESULTS: There were 454 infrainguinal bypass procedures analyzed. Demographics and baseline characteristics were similar, except congestive heart failure and diabetes were more common in the infection group. Presence of foot infection had no impact on mortality (hazard ratio [HR], 0.78; P = .243). Significant predictors of long-term mortality included increasing age, hypoalbuminemia, and congestive heart failure; preoperative use of clopidogrel was protective. Presence of foot infection was an independent predictor of major amputation. In the multiple regression model, the presence of foot infection was independently associated with amputation rate (HR, 2.14; 95% confidence interval, 1.42-3.22; P < .001); use of venous conduit and increasing age and body mass index were protective. Foot infection was an independent predictor of prolonged LOS (mean LOS was 1.54 days longer in patients with vs those without infection; P = .001). Other independent predictors of prolonged LOS included intraoperative blood loss and reoperation; history of continuous preoperative aspirin use and normal baseline renal function and albumin levels were associated with decreased LOS. Readmission was influenced by reoperation (odds ratio [OR], 2.51; P < .001) but not by presence of foot infection (OR, 1.21; P = .349). There was a strong trend for prolonged wound healing time in patients with diabetes (HR, 1.58; P = .05) but not in those with foot infection (OR, 0.74; P = .36). CONCLUSIONS: Among patients requiring infrainguinal bypass for limb-threatening ischemia, infection was more common in patients with diabetes and was a significant predictor of major amputation and prolonged LOS. Infection was not predictive of mortality, wound healing time, or readmission. These findings lend support to the inclusion of infection in risk stratification schemes for patients with chronic limb-threatening ischemia, as recommended in the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system, because of its adverse impacts on limb salvage.

Results of One-Stage or Staged Amputations of Lower Limbs Consequent to Critical Limb Ischemia and Infection.

BACKGROUND: Amputations of lower limbs can be conducted as one-stage amputation (OSA) or staged amputation (SA) procedures. The objective of this study was to analyze technical success and mortality rates of both techniques, as well as factors that might influence outcomes in patients with critical limb ischemia (CLI). METHODS: A retrospective study of 185 consecutive patients with CLI who underwent amputations in the period 2004-2011. Primary end points were rates of technical success (healing without dehiscence or reintervention) and mortality. The influence on outcomes of demographic data, clinical status, and comorbidities was also analyzed by logistic regression. RESULTS: A total of 101 SA (91 patients) and 106 OSA (94 patients) were analyzed. SA had proportionally higher success rate (SA 77.2% vs. OSA 66.0%, P = 0.0253), lower perioperative mortality rate (SA, 10.9% vs. OSA, 20.7%, P = 0.0247), and lower 30-day mortality rate (SA, 12.2% vs. OSA, 23.8%, P = 0.0220) in spite of more cases with Rutherford classes 5 and 6 (SA, 87.1% vs. OSA, 72.6%, P = 0.0047), diabetes (71.2% vs. 55.6%, P = 0.0076), and infection (44.5% vs. 28.3%, P = 0.0061). Logistic regression demonstrated that in SA, success was more frequent in patients with diabetes who did not use insulin (P = 0.0072), in those with transfemoral amputations (P = 0.0392), with no coronary artery disease (P = 0.0053), and in foot infection (P = 0.0446), while for OSA success was more frequent in nondiabetic patients (P = 0.0077), limbs without infection (P = 0.0298), amputations at foot level (P = 0.0155), or transfemoral amputations (P = 0.0030). CONCLUSIONS: SA had a higher rate of technical success and lower mortality rates than OSA, even with greater number of patients with diabetes and more severe cases of ischemia and infection. However, prospective studies comparing both techniques are needed for further evidence.

Improvement of wound healing by regulated oxygen-enriched negative pressure-assisted wound therapy in a rabbit model.

BACKGROUND: Development of drug therapies and other techniques for wound care have resulted in significant improvement of the cure rate and shortening of the healing time for wounds. A modified technique of regulated oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) has been reported. AIM: To evaluate the efficacy and impact of RO-NPT on wound recovery and inflammation. METHODS: Infected wounds were established on 40 adult female white rabbits, which were then randomized to one of four groups: O2 group, regulated negative pressure-assisted wound therapy (RNPT) group, regulated oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) group and healthy control (HC) group. Each day, the O2 group was treated with a constant oxygen supply (1 L/min) to the wound, while the RNPT group was treated with continuous regulated negative pressure (70 ± 5 mmHg) and the RNPT + O2 group was treated with both. The HC group was treated with gauze dressing alone, which was changed every day. Leucocyte count, colony count and wound-healing rate were calculated. Levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-8 were evaluated by ELISA. RESULTS: RO-RNPT significantly decreased bacterial count and TNF-α level, and increased the wound-healing rate. IL-1ß, IL-8 and leucocyte count had a tendency to increase in the early phase of inflammation and a tendency to decrease in the later phase of inflammation in the RO-RNPT group. CONCLUSIONS: RO-NPT therapy assisted wound recovery and inflammation control compared with the RNPT and oxygen-enriched therapies. RO-NPT therapy also increased levels of IL-1ß and IL-8 and attenuated expression of TNF-α in the early phase of inflammation.

Determinants of midterm functional outcomes, wound healing, and resources used in a hospital-based limb preservation program.

OBJECTIVE: The objective of this study was to assess midterm functional status, wound healing, and in-hospital resource use among a prospective cohort of patients treated in a tertiary hospital, multidisciplinary Center for Limb Preservation. METHODS: Data were prospectively gathered on all consecutive admissions to the Center for Limb Preservation from July 2013 to October 2014 with follow-up data collection through January 2016. Limbs were staged using the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) threatened limb classification scheme at the time of hospital admission. Patients with nonatherosclerotic vascular disorders, acute limb ischemia, and trauma were excluded. RESULTS: The cohort included 128 patients with 157 threatened limbs; 8 limbs with unstageable disease were excluded. Mean age (±standard deviation [SD]) was 66 (±13) years, and median follow-up duration (interquartile range) was 395 (80-635) days. Fifty percent (n = 64/128) of patients were readmitted at least once, with a readmission rate of 20% within 30 days of the index admission. Mean total number of admissions per patient (±SD) was 1.9 ± 1.2, with mean (±SD) cumulative length of stay (cLOS) of 17.1 (±17.9) days. During follow-up, 25% of limbs required a vascular reintervention, and 45% developed recurrent wounds. There was no difference in the rate of readmission, vascular reintervention, or wound recurrence by initial WIfI stage (P > .05). At the end of the study period, 23 (26%) were alive and nonambulatory; in 20%, functional status was missing. On both univariate and multivariate analysis, end-stage renal disease and prior functional status predicted ability to ambulate independently (P < .05). WIfI stage was associated with major amputation (P = .01) and cLOS (P = .002) but not with time to wound healing. Direct hospital (inpatient) cost per limb saved was significantly higher in stage 4 patients (P < .05 for all time periods). WIfI stage was associated with cumulative in-hospital costs at 1 year and for the overall follow-up period. CONCLUSIONS: Among a population of patients admitted to a tertiary hospital limb preservation service, WIfI stage was predictive of midterm freedom from amputation, cLOS, and hospital costs but not of ambulatory functional status, time to wound healing, or wound recurrence. Patients presenting with limb-threatening conditions require significant inpatient care, have a high frequency of repeated hospitalizations, and are at significant risk for recurrent wounds and leg symptoms at later times. Stage 4 patients require the most intensive care and have the highest initial and aggregate hospital costs per limb saved. However, limb salvage can be achieved in these patients with a dedicated multidisciplinary team approach.

A bioluminescent Pseudomonas aeruginosa wound model reveals increased mortality of type 1 diabetic mice to biofilm infection.

OBJECTIVE: To examine how bacterial biofilms, as contributing factors in the delayed closure of chronic wounds in patients with diabetes, affect the healing process. METHOD: We used daily microscopic imaging and the IVIS Spectrum in vivo imaging system to monitor biofilm infections of bioluminescent Pseudomonas aeruginosa and evaluate healing in non-diabetic and streptozotocin-induced diabetic mice. RESULTS: Our studies determined that diabetes alone did not affect the rate of healing of full-depth murine back wounds compared with non-diabetic mice. The application of mature biofilms to the wounds significantly decreased the rate of healing compared with non-infected wounds for both non-diabetic as well as diabetic mice. Diabetic mice were also more severely affected by biofilms displaying elevated pus production, higher mortality rates and statistically significant increase in wound depth, granulation/fibrosis and biofilm presence. Introduction of a mutant Pseudomonas aeruginosa capable of producing high concentrations of cyclic di-GMP did not result in increased persistence in either diabetic or non-diabetic animals compared with the wild type strain. CONCLUSION: Understanding the interplay between diabetes and biofilms may lead to novel treatments and better clinical management of chronic wounds.

A Reliability Study Using a Long-Wave Infrared Thermography Device to Identify Relative Tissue Temperature Variations of the Body Surface and Underlying Tissue.

OBJECTIVE: This study assesses the ability of the Scout (WoundVision LLC, Indianapolis, Indiana), an FDA-approved visual and thermal imaging device and software analysis tool, to provide clinicians with a reliable and reproducible way to incorporate long-wave infrared thermography and relative temperature differential into clinical wound assessment by consistently identifying control areas against which to measure wound temperature. METHODS: This laboratory-based study utilized 3 adult wound care professionals experienced in control area selection. Twenty-six previously collected wound images were used for the study. The 3 readers placed a control area on each of the 26 wounds 3 different times (n = 78 independent placements) to establish within-reader agreement. To establish between-reader agreement, the readers again placed a control area on each of the 26 wounds (n = 26 independent placements). OUTCOME MEASURES: This study evaluates 2 aspects of the Scout device's reliability: (1) within- and between-reader agreement of initial patient encounter control area images and (2) between-reader agreement of follow-up encounter control area images. RESULTS: The control area measurements were very consistent both within (percent coefficient of variation [%CV] approximately 1%) and between readers (%CV approximately 2%). The average maximum temperature within-reader %CV was 1.14% and the between-reader variation was %CV 1.97%. The average minimum temperature had a within-reader %CV of 1.1% and the between-reader coefficient of variation was 2.01%. The within- and between-reader average difference in mean temperature was 0.14° C and 0.29° C, respectively. The largest mean temperature difference observed within-readers was 0.68° C, and the smallest difference was 0.01° C. The largest difference observed in between-reader mean temperature was 0.96° C, and the smallest was 0.03° C. CONCLUSIONS: This study demonstrates that clinicians can repeatedly and reliably perform a relative temperature differential analysis using the Scout device to determine an appropriate control area for wound temperature assessment.

Relative Temperature Maximum in Wound Infection and Inflammation as Compared with a Control Subject Using Long-Wave Infrared Thermography.

OBJECTIVE: The purpose of this retrospective case series was to determine whether a long-wave infrared thermography (LWIT, or thermal imaging) camera can detect specific temperature changes that are associated with wound infection and inflammation as compared with normal control subjects with similar anatomical wound locations. DESIGN: A retrospective, observational, collective, multiple case series of patients who underwent digital and thermal imaging of wounds in various states. SETTING: The subjects were selected from multiple sites including an outpatient wound care clinic, a wound care physician's office, a rehabilitation hospital, and a home healthcare organization. PATIENTS: Six subjects were selected for inclusion, including 2 each for the infection, inflammation, and normal control groups. MAIN OUTCOME MEASURE: The study collected relative temperature maximums as obtained and recorded by LWIT and digital imaging. MAIN RESULTS: In this case series, the authors demonstrate the use of an FDA-approved Scout (WoundVision, Indianapolis, Indiana) dual-imaging long-wave infrared and digital cameras to analyze images of wounds. In the 2 cases with clinically diagnosed wound infection, LWIT showed an elevation of temperature as evidenced by a maximum temperature differential between the wound and healthy skin of +4° C to 5° C. Also, LWIT was able to identify relative thermal changes of +1.5° C to 2.2° C in subjects presenting with clinical signs of inflammation. In addition, LWIT was able to show that the normal control subjects without diagnosis of infection or signs of inflammation had relative temperature differentials of +1.1° C to 1.2° C. Finally, LWIT could detect adequate treatment of infected wounds with antibiotics as evidenced by a return to normal temperature differences gradient of +0.8° C to 1.1° C, as compared with normal control subjects with wounds in the same anatomical location. CONCLUSIONS: Long-wave infrared thermography can collect and record objective data, including relative temperature maximums associated with infection, inflammation, and normal healing wounds.

[Treatment of purulent wounds with wound dressing on a foamy basis with Hydrofiber technology]. / Lechenie gnoinykh ran s primeneniem ranevykh pokrytii na pennoi osnove s tekhnologiei Gidrofaiber.

AIM: to evaluate the effectiveness of modern approaches to the treatment of purulent wounds with the use of foam-based wound coatings with the Hydrofiber technology in comparison with the traditional method of wounds. MATERIAL AND METHODS: An analysis of the results of treatment of 34 patients with purulent wounds of various etiologies was performed. Patients were divided into two groups: control and basic. In the main group, local treatment of wounds was carried out using a foam-based wound coating with Hydrofiber technology. In the control group, local treatment of wounds was carried out using traditional methods with the use of gauze bandages. RESULTS: With the use of foam-based wound coatings with Hydrofiber® technology, the inflammation process in the wound and surrounding tissues is more rapidly eliminated, the periods of purification and microbial decontamination in the purulent focus are reduced.

Validation of the Wound, Ischemia, foot Infection (WIfI) classification system in nondiabetic patients treated by endovascular means for critical limb ischemia.

BACKGROUND: The Society for Vascular Surgery Lower Extremity Guidelines Committee developed the Wound, Ischemia, foot Infection (WIfI) a classification system to predict the amputation risk in patients with critical limb ischemia (CLI). A number of published studies have already evaluated its prognostic value. However, most of the included patients were diabetic, and the validation was done independent of the revascularization procedure. This single-center study evaluated the prognostic value of WIfI stages in nondiabetic patients treated by endovascular means. METHODS: A retrospective analysis was performed of prospectively collected data of nondiabetic patients treated by endovascular means between January 2013 and September 2014. All patients were classified according to their wound status, ischemia index, and extent of foot infection to four classes: very low risk, low risk, moderate risk, and high risk. Comorbidities and vascular lesions for each group were analyzed. The prognostic value of WIfI was analyzed based on the amputation-free survival, overall survival rate, and freedom from amputation at 12 months. RESULTS: Data from 302 CLI patients treated in the study period were reviewed. A total of 219 patients (73%) underwent an endovascular intervention, and among them, 126 nondiabetic patients (58%) were enrolled in this study. Most patients were classified as low risk (33%), and the prevalence of very low-risk, moderate-risk, and very high-risk patients was 23%, 23%, and 21%, respectively. The modified Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT III) score was statistically significantly higher in the high-risk group (5.2 ± 2.4) than in the very low-risk, low-risk, and moderate-risk groups (4.3 ± 2.5, 3.5 ± 2.3, 4.5 ± 2.2, respectively; P = .048). One major amputation (1%) was performed during the hospital stay in a high-risk patient. Mean follow-up was 14 ± 8 months. The amputation-free survival at 12 months was 87%, 81%, 81%, and 62%, in the very low-risk, low-risk, moderate risk, and very high-risk groups, respectively (P = .106). The difference was statistically significant between the very low-risk and high-risk groups (hazard ratio, 3.4; 95% confidence interval, 1.1-10.3; P = .029). A similar trend was also observed for 1-year survival between the very low-risk and the high-risk groups (87%, 84%, 81%, 65%; P = .166). The amputation rate during the follow-up time was 0%, 2% (n = 6), 3% (n = 5), and 12% (n = 9) for the very low-risk, low-risk, moderate-risk, and very high-risk groups, respectively (P = .033). CONCLUSIONS: The WIfI classification system predicted the amputation risk and survival in this highly selected group of nondiabetic CLI patients treated by endovascular means, with a statistically significant difference between very low-risk and high-risk patients already at 1 year.

The Society for Vascular Surgery lower extremity threatened limb classification system based on Wound, Ischemia, and foot Infection (WIfI) correlates with risk of major amputation and time to wound healing.

OBJECTIVE: The purpose of this study was to evaluate whether the new Society for Vascular Surgery (SVS) Wound, Ischemia, and foot Infection (WIfI) classification system correlates with important clinical outcomes for limb salvage and wound healing. METHODS: A total of 201 consecutive patients with threatened limbs treated from 2010 to 2011 in an academic medical center were analyzed. These patients were stratified into clinical stages 1 to 4 on the basis of the SVS WIfI classification. The SVS objective performance goals of major amputation, 1-year amputation-free survival (AFS) rate, and wound healing time (WHT) according to WIfI clinical stages were compared. RESULTS: The mean age was 58 years (79% male, 93% with diabetes). Forty-two patients required major amputation (21%); 159 (78%) had limb salvage. The amputation group had a significantly higher prevalence of advanced stage 4 patients (P < .001), whereas the limb salvage group presented predominantly as stages 1 to 3. Patients in clinical stages 3 and 4 had a significantly higher incidence of amputation (P < .001), decreased AFS (P < .001), and delayed WHT (P < .002) compared with those in stages 1 and 2. Among patients presenting with stage 3, primarily as a result of wound and ischemia grades, revascularization resulted in accelerated WHT (P = .008). CONCLUSIONS: These data support the underlying concept of the SVS WIfI, that an appropriate classification system correlates with important clinical outcomes for limb salvage and wound healing. As the clinical stage progresses, the risk of major amputation increases, 1-year AFS declines, and WHT is prolonged. We further demonstrated benefit of revascularization to improve WHT in selected patients, especially those in stage 3. Future efforts are warranted to incorporate the SVS WIfI classification into clinical decision-making algorithms in conjunction with a comorbidity index and anatomic classification.

Cellular and molecular mechanisms of repair in acute and chronic wound healing.

A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments.

Approach to chronic wound infections.

Infection is the likeliest single cause of delayed healing in healing of chronic open wounds by secondary intention. If neglected it can progress from contamination to colonization and local infection through to systemic infection, sepsis and multiple organ dysfunction syndrome, and it can be life-threatening. Infection in chronic wounds is not as easy to define as in acute wounds, and is complicated by the presence of biofilms. There is, as yet, no diagnostic for biofilm presence, but it contributes to excessive inflammation - through excessive and prolonged stimulation of nitric oxide, inflammatory cytokines and free radicals - and activation of immune complexes and complement, leading to a delay in healing. Control of biofilm is a key part of chronic wound management. Maintenance debridement and use of topical antimicrobials (antiseptics) are more effective than antibiotics, which should be reserved for treating spreading local and systemic infection. The continuing rise of antimicrobial resistance to antibiotics should lead us to reserve their use for these indications, as no new effective antibiotics are in the research pipeline. Antiseptics are effective through many mechanisms of action, unlike antibiotics, which makes the development of resistance to them unlikely. There is little evidence to support the theoretical risk that antiseptics select resistant pathogens. However, the use of antiseptic dressings for preventing and managing biofilm and infection progression needs further research involving well-designed, randomized controlled trials.

Burn wound healing and treatment: review and advancements.

Burns are a prevalent and burdensome critical care problem. The priorities of specialized facilities focus on stabilizing the patient, preventing infection, and optimizing functional recovery. Research on burns has generated sustained interest over the past few decades, and several important advancements have resulted in more effective patient stabilization and decreased mortality, especially among young patients and those with burns of intermediate extent. However, for the intensivist, challenges often exist that complicate patient support and stabilization. Furthermore, burn wounds are complex and can present unique difficulties that require late intervention or life-long rehabilitation. In addition to improvements in patient stabilization and care, research in burn wound care has yielded advancements that will continue to improve functional recovery. This article reviews recent advancements in the care of burn patients with a focus on the pathophysiology and treatment of burn wounds.

Validation of commercially available infrared thermometers for measuring skin surface temperature associated with deep and surrounding wound infection.

OBJECTIVE: Increased local skin temperature is a classic sign of wound infection, repetitive trauma, and deep inflammation. Noncontact infrared thermometers can help to detect increases in skin surface temperatures; however, most scientifically tested devices are far too expensive for everyday wound care providers to use in routine clinical practice. This noninferiority study was conducted in an attempt to determine whether 4 less expensive, commercially available noncontact infrared thermometers have a similar level of accuracy as the scientifically accepted Exergen DermaTemp 1001 (Exergen Products, Watertown, Massachusetts). DESIGN, SETTING, AND PARTICIPANTS: Using an observational study design, participants with open wounds were randomly selected from a chronic wound clinic (n = 108). Demographic data and wound location were documented for all participants. Skin temperatures were recorded using 5 noncontact infrared thermometers under consistent environmental conditions. The thermometer brands were as follows: Exergen DermaTemp, Mastercool MSC52224-A (Mastercool Inc, Randolph, New Jersey), ATD Tools 70001 Infrared Thermometer (ATD Tools Inc, Wentzville, Missouri), Mastercraft Digital Temperature Reader (Mastercraft Canada, Toronto, Ontario, Canada), and Pro Point Infrared Thermometer (Princess Auto, Winnipeg, Manitoba, Canada). Data analysis was based on the skin surface temperature difference (ΔT in degrees Fahrenheit) between the wound site and an equivalent contralateral control site. OUTCOME MEASURES: One-way analysis of variance was used to compare the mean ΔT values for all the 5 thermometers, followed by post hoc analysis. Demographic data were analyzed using descriptive statistics. Interrater reliability was assessed for consistency using the intraclass correlation coefficient. MAIN RESULTS: No statistical difference was reported between the ΔT values for the 5 different thermometers (F4,514 = 0.339, P = .852). Post hoc analysis showed no significant difference when the thermometers were compared with the Exergen DermaTemp 1001, and Mastercool MSC52224-A (P = .987), ATD Tools 70001 Infrared Thermometer (P = .985), Mastercraft Digital Temperature Reader (P = .972), and Pro Point Infrared Thermometer (P = .774). The results for intraclass correlation demonstrated a high reliability and agreement between raters, as the intraclass correlation coefficient values for all thermometers were greater than 0.95. CONCLUSIONS: The results of this study demonstrate that less expensive, industrial-grade noncontact infrared thermometers have reliable temperature readings to identify and quantify the temperature gradients that along with other signs may be associated with deep and surrounding wound infection or tissue injury due to repeated microtrauma.

Contrasting mechanisms by which social isolation and restraint impair healing in male mice.

Stress modulates vital aspects of immune functioning in both human and non-human animals, including tissue repair. For example, dermal wounds heal more slowly and are associated with prolonged inflammation and increased bacterial load in mice that experience chronic physical restraint. Social stressors also negatively affect healing; however, previous studies suggest that the affected healing mechanisms may be stress model-specific. Here, the effects of either social isolation or physical restraint on dermal wound healing (3.5 mm wounds on the dorsum) were compared in hairless male mice. Social isolation beginning 3 weeks prior to wounding delayed healing comparably to physical restraint (12 h/day for eight days), in spite of marked differences in metabolic and hormonal consequences (i.e. body mass) between the two stress models. Additionally, isolated mice exhibited reductions in wound bacterial load and inflammatory gene expression (interleukin-1beta [IL-1ß], monocyte chemoattractant protein [MCP]), whereas restraint significantly increased both of these parameters relative to controls. Experimentally augmenting bacterial concentrations in wounds of isolated mice did not ameliorate healing, whereas this treatment accelerated healing in controls. This work indicates that social isolation and restraint stressors comparably impair healing, but do so through disparate mechanisms and at different phases of healing.