The International Journal of Lower Extremity Wounds

There are a variety of dressings for wound healing. For this reason, research can assist in the choice and proper use of the intervention. This current view of the effectiveness of dressing on diabetic foot ulcers (DFUs) in patients with type 2 diabetes mellitus. This study is a systematic review of clinical trials selected in 4 databases: PubMed, Scopus, Web of Science, and Cochrane. Studies without language restriction, published between 2009 and 2020, were included. The search resulted in the identification of 5651 articles, of which 58 met all inclusion criteria. Among these, 2 biomaterials (D-acellular dermal matrix and keratinocyte) and phenytoin were highlighted for achieving healing rates of 100% and 95.82% ± 2.22%, respectively. The literature presents several alternatives with different actions, cure rates, reduction rates, and varied cost benefits. The growth in the use of biomaterials for the treatment of DFU can be seen in this study.

Dynamic optical coherence tomography (D-OCT) is a relatively new technique that may be used to study the substructures in the retina, in the skin and its microcirculation. Furthermore, D-OCT is a validated method of imaging blood flow in skin microcirculation. The skin around venous and mixed arterio-venous ulcers was imaged and found to have tortuous vessels assumed to be angiogenic sprouts, and classified as dots, blobs, coils, clumps, lines, and curves. When these images were analyzed and measurements of vessel density were made, it was observed that the prevalence of coils and clumps in wound borders was significantly greater compared with those at wound centers. This reinforced the belief of inward growth of vessels from wound edge toward wound center which, in turn, reposed confidence in following the wound edge to study healing. D-OCT imaging permits the structure and the function of the microcirculation to be imaged, and vessel density measured. This offers a new vista of skin microcirculation and using it, to better understand angiogenesis in chronic wounds.

Chronic foot ulcers have extensive consequences for diabetic patients’ quality of life and increase risks of amputation and death. The aim of this trial was to assess the feasibility of conducting a larger clinical trial to evaluate the clinical effect of inforatio technique on healing of diabetic foot ulcers (DFUs). Inforatio technique is a novel minimal invasive procedure where small cuts are made on wound beds with punch biopsy tools. This study was a feasibility trial conducted at an outpatient wound care clinic at Zealand University Hospital. Twelve patients with DFUs were included. During a 90-day follow-up, participants visited the clinic 5 times and received inforatio technique twice. Feasibility was assessed with regard to recruitment, acceptability, burden, benefits, protocol adherence, and adverse events. The recruitment rate was 1 patient per eighth day (95% confidence interval [CI] = [4th-13th]), and the retention rate was 100% (95% CI = [74-100]). During follow-up, healing was observed for 4 ulcers (33%, 95% CI = [10-65]) with a mean time for healing of 59 days (range, 22-89) (95% CI = [5-113]). Five ulcers had a reduction of wound area and 3 ulcers had an increase in area from baseline to 90-day follow-up. No temporal relationship was found between inforatio application and wound area increase. There were no patient-reported harmful effects and no adverse events with probable relation to inforatio technique. Patient acceptability and participant adherence were promising. Thus, a larger clinical trial for evaluating the clinical effect of inforatio technique is considered feasible to conduct.

Distally based sural fasciocutaneous (DBSF) flaps are widely used for reconstructing soft tissue defects of the foot. The purpose of this paper was to compare the clinical efficacy of the use of flaps to repair defects in areas proximal and distal to the level of the tarsometatarsal joints in a relatively large number of patients and to analyze the effects of factors on the risk of developing partial necrosis of the flaps. Between April 2001 and December 2019, a total of 355 DBSF flaps were utilized to cover soft tissue defects in the foot. According to the furthest location of the defects reconstructed with the flaps, the flaps were divided into the proximal foot group (n = 260) and the distal foot group (n = 95). The partial necrosis rates, their influencing factors, and the clinical outcomes of the procedure were compared between the two groups. In the proximal foot group, the partial necrosis rate (6.2%, 16 of 260) was significantly lower than that in the distal foot group (14.7%, 14 of 95) (P < .05). The proportion of successful coverage of the defects using the flaps alone or in combination with a simple salvage treatment was comparable between the groups (P > .05). The ratio of unfavorable conditions in the distal foot group was higher than that in the proximal foot group (P < .05). DBSF flaps can be effectively utilized to repair defects in the proximal and distal areas of the foot. The use of a DBSF flap to repair defects in the proximal areas of the foot is superior to the use of DBSF flaps for repairing defects in the distal areas of the foot in terms of reliable survival of the flap.

The supposition is that the usage of fibrin rich in leukocytes and platelets advanced (A-PRF) in ulcerative osteomyelitis of the diabetic foot allows rehabilitation from this critical illness. In this investigation, the focus was to normalize the use of platelet-rich fibrin (PRF) in patients with osteomyelitis not amputated, to use this second-generation platelet concentrate as a regeneration enabler. The researchers submitted and utilized A-PRF membranes (1300 g × 8 min) in 7 patients (all diabetics) with osteomyelitis and cutaneous injury for 6 months. The membranes, in combination with the supernatant fluid produced by stress, have been integrated into the skin lesion down to the bone after surgical debridement. The advancement of the lesions after some period of time has been analyzed. All 7 subjects had a probe-to-bone positive assay; magnetic resonance imaging indicated cortico-periosteal coagulation and/or foci of cortico-spongeous osteolysis contiguous to the lesion. Gram-positive bacteria were identified in our procedures in 52% of cases. Gram + Cocci, for example, Staphylococcus aureus (15.6%), β-hemolytic Streptococci (12.1%), Streptococcus viridans (7.1%), and Gram-negative bacteria, for example, Pseudomonas (10.6%), Proteus (7.8%), Enterobacter (5.7%) were present. Candida albicans was active in 2.8% of cases. The blood count showed no relevant differences. To date, cutaneous lesions have been cured in 6 of the 7 subjects treated (1 patient for more than 6 years) without any evidence of infection or recurrence. The results obtained on our subjects indicate that PRF membranes may be a therapeutic option in this problematic disease. In fact, this clinical approach may have the potential to promote the healing of diabetic skin lesions with osteomyelitis.

Microbiological cultures of per-wound bone biopsies have shown a lack of correlation and a high rate of false-negative results when compared with bone biopsy cultures in diabetic foot osteomyelitis. The selection of samples from the area of active osteomyelitis, which contains a complete census of the microorganisms responsible for the infection, is essential to properly guide antimicrobial treatment. We aimed to comparatively evaluate the quantitative and qualitative cultures taken from different areas, in metatarsal heads resected for osteomyelitis. For this purpose, we consecutively selected 13 metatarsal heads from 12 outpatients with plantar ulcers admitted to our diabetic foot unit. Metatarsal heads were divided transversally into 3 portions: plantar (A), central (B), and dorsal (C), and the 39 resulting samples were cultured. Qualitative and quantitative microbiological analysis was performed, and the isolated species and bacterial load, total and species specific, were compared between the 3 metatarsal bone segments. The primary outcome of the study was the bacterial diversity detected in the different bone sections. Cultures were positive in 12 of the 13 included metatarsal heads (92%). A total of 34 organisms were isolated from all specimens. Ten of the 12 cultures (83%) were polymicrobial. Ten of the 13 metatarsal heads (77%) had identical microbiological results in each of the 3 bone sections. The largest number of microorganisms was found in the central section. The overall concordance between sections was 91%. The predominant microorganisms were coagulase-negative staphylococci (41%). Statistical differences were not found in the bioburden between sections (range 3.25-3.41 log₁₀ colony-forming unit/g for all sections; P = .511). The results of our study suggest that microorganisms exhibit a high tendency to spread along the metatarsal bone and that the degree of progression along the bone is species dependent. The central portions of metatarsal bones tend to accumulate a higher diversity of species. Thus, we recommend this area of bone for targeted biopsy in patients with suspected osteomyelitis.

“Light amplification by stimulated emission of radiation” or more commonly known as Laser has become very popular in the field of dermatology and aesthetic medicine over the past decades. For the treatment of wound healing, a combination of different wavelengths for laser therapy has been introduced which includes 660, 800, and 970 nm. The aim of this study was to note wound healing utilizing photobiomodulation as an adjunct therapy by measuring the wound size in terms of length and width (area measurement). Study participants were selected randomly from a pool of patients who were attending for their routine follow-up visits in the Wound Care Unit in Hospital Kuala Lumpur. Eleven patients with chronic wounds of different etiologies, ie, diabetic foot ulcer and nonhealing ulcer, were recruited for this study . Wound assessment was done prior to cleansing using distilled water and followed by debridement if necessary. Subsequently, the laser technician and patients used protective goggles before applying a super intense continuous flow of laser with 3 wavelengths, ie, 660, 800, and 970 nm with 30 kJ of energy with the handpiece over a 3 min period whereby it is focused on the wound milieu and then rotated around the periwound area. There were 9 diabetic foot ulcers and 2 nonhealing ulcers treated with photobiomodulation as an adjunct therapy. All wounds were managed with the standard of care. Three wounds ie, 3 diabetic foot ulcers and 1 nonhealing ulcer were closed completely. Meanwhile, the other 7 ulcers are at 68.2% to 99% in terms of wound area reduction and new granulomatous tissue was present indicating high healing potential. Therefore, the photobiomodulation was effective as an adjunct in the management of diabetic foot and nonhealing ulcers in this case series. A larger sample size would be able to show the significance of this finding.

We aimed to determine pathogen microorganisms, their antimicrobial resistance patterns, and the effect of initial treatment on clinical outcomes in patients with diabetic foot infection (DFI). Patients with DFI from 5 centers were included in this multicenter observational prospective study between June 2018 and June 2019. Multivariate analysis was performed for the predictors of reinfection/death and major amputation. A total of 284 patients were recorded. Of whom, 193 (68%) were male and the median age was 59.9 ± 11.3 years. One hundred nineteen (41.9%) patients had amputations, as the minor (n = 83, 29.2%) or major (n = 36, 12.7%). The mortality rate was 1.7% with 4 deaths. A total of 247 microorganisms were isolated from 200 patients. The most common microorganisms were Staphylococcus aureus (n = 36, 14.6%) and Escherichia coli (n = 32, 13.0%). Methicillin resistance rates were 19.4% and 69.6% in S aureus and coagulase-negative Staphylococcus spp., respectively. Multidrug-resistant Pseudomonas aeruginosa was detected in 4 of 22 (18.2%) isolates. Extended-spectrum beta-lactamase-producing Gram-negative bacteria were detected in 20 (38.5%) isolates of E coli (14 of 32) and Klebsiella spp. (6 of 20). When the initial treatment was inappropriate, Klebsiella spp. related reinfection within 1 to 3 months was observed more frequently. Polymicrobial infection (p = .043) and vancomycin treatment (p = .007) were independent predictors of reinfection/death. Multivariate analysis revealed vascular insufficiency (p = .004), hospital readmission (p = .009), C-reactive protein > 130 mg/dL (p = .007), and receiving carbapenems (p = .005) as independent predictors of major amputation. Our results justify the importance of using appropriate narrow-spectrum empirical antimicrobials because higher rates of reinfection and major amputation were found even in the use of broad-spectrum antimicrobials.

Substance P (SP), an endogenous neuropeptide, mediates intracellular signaling, mainly through a tachykinin receptor. The tachykinin receptors family consists of neurokinin-1 (NK-1), neurokinin-2 (NK-2), and neurokinin-3 receptors. Our previous studies on SP have shown its wound healing potentials. But the exact mechanism of wound healing by SP is not exactly known. In view of this, the present study was aimed at evaluating the in vitro wound healing effect of SP alone and in the presence of NK-1, NK-2, and both receptor antagonists. Scratch assay, transwell assay, and tumor growth factor-beta 1 (TGF-β1) assay were performed on buffalo fetal fibroblast culture. The cotreatment of fibroblast cultures with SP alone during the 24 h caused the significant proliferation and migrations of cells in both horizontal and vertical directions. The SP in the presence of spantide II (NK-1 antagonist) failed to stimulate this migration. The treatment of cells with SP in the presence of NK-2 antagonist treatment also showed a significant reduction of migration of cells with respect to SP treatment alone. The SP in the presence of both NK-1 and NK-2 antagonists failed to stimulate the horizontal migration of cells and most of the ineffectiveness of SP was observed in this combination. The TGF-β1 levels were significantly higher in the supernatants of cells that were exposed to SP alone. All other treatments have significantly lower TGF-β1 levels than SP alone treatment. It is concluded that different actions on fibroblast cells by SP were mainly mediated through the NK-1 receptor.

Silver formulation has been used for external use of burn wounds for several decades, mainly including silver sulfadiazine (SSD), nanosilver dressing (NSD), and silver ion dressing (SID). At present, there is no simultaneous comparison of the effects of silver formulation on burn wounds. The databases were retrieved in an orderly manner from the dates of their establishment to May 2020, including PubMed, the Cochrane Library, Web of Science, and Clinical Trials. Then a network meta-analysis was conducted using R and RevMan 5.1 software. A total of 13 randomized controlled trials (RCTs) involving 945 patients with burns were included. A pairwise meta-analysis of the results was presented: the wound healing time in the SID or NSD treatment group was less than that in the SSD group; and in relieving the pain there was a statistical difference between the SSD, SID, or NSD groups. Network meta-analysis of the results was presented: the wound healing time and relieving the pain in the SID or NSD treatment group were less than that in the SSD group, but there was no statistical difference between the SID and NSD groups. The possibility of NSD in the wound healing time being the best treatment was 75.2%, followed by SID (36.6%), and finally SSD (1.1%); and the possibility of NSD being the best relieving the pain was 83.5%; followed by SID (60.0%), and finally SSD (16.3%). According to the evidence, treatment for burns with NSD can improve the wound healing time and relieve the pain of wounds.

This study retrospectively analyzes all consecutive patients who underwent during a year hospital readmissions, defined as an admission to a hospital within 30 days of discharge, to an Italian Internal Medicine ward. All these data were compared with those from patients who underwent only 1 hospital admission in the same period. The aim of this study was to identify potential novel risk factors for hospital readmissions. In 2018, a total of 3012 patients were hospitalized. Among these, 14.1% (n = 426; mean age, 79.7 ± 11.9; range, 23-100) were defined as readmissions; data were compared with controls (n = 420; 13.9%; mean age, 75.9 ± 14.7; range, 22-99) who had only 1 hospitalization. Cases showed a significantly higher prevalence than controls regarding cerebrovascular disease (77.2% vs 48.1%), cognitive impairment (51.8% vs 26.9%), congestive heart failure (47.6% vs 20.2%), chronic kidney disease (31.7% vs 13.1%), and chronic obstructive pulmonary disease (23.0% vs 14.5%). Skin ulcers were significantly more prevalent among cases (45.1% vs 17.6%). Diagnosis-related group (DRG) analysis showed a higher proportion of “infectious disease” (24.4% vs 15.0%) among the cases than in controls. Despite skin ulcers were very frequent among cases and controls (45.1% vs 17.6%), they were codified as “skin wound” DRG only in 1.4% and 0.2%, respectively. At the DRGs analysis, sepsis (31.6% vs 19.1%), pneumonia (17.1% vs 7.6%), and kidney failure (9.6% vs 3.8%) represented the main significant cause of death in cases compared to controls. Our study confirms that readmissions to Internal Medicine departments are related to the severity of chronic diseases affecting patients. Skin ulcers are present in about half of patients who will be early readmitted within 30 days, but they are almost never reported in DRGs, so more accurate coding is needed. Key challenges for the future are sepsis prevention measures and investing resources in chronic disease assistance, including skin ulcer chronic management.

We analyzed a retrospective cohort of 150 patients with diabetic foot infections (DFIs) who underwent surgical treatment to determine long-term outcomes. The median follow-up of the series was 7.6 years. Cox’s proportional hazards model for survival time was performed and hazard ratios (HRs) were estimated. Survival times were plotted using the Kaplan–Meier method. Fifteen patients (10%) required readmission after discharge from the hospital for a recurrence of the infection. Ninety patients (60%) had re-ulcerations. Forty-nine (54.4% of those re-ulcerated) required new admission and 24 of them (26.6% of those re-ulcerated) finally required a new amputation. Overall cumulative survival rates at 1, 5, and 8 years were 95%, 78%, and 64%, respectively. Predictive variables of long-term mortality were insulin treatment (HR: 2.0, 95% CI: 1.1-3.6, P = .01), female sex (HR: 3.1, 95% CI: 1.7-5.3, P<.01) and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² (HR: 2.2, 95% CI: 1.1-4.2, P = .01). In conclusion, patients undergoing surgical treatment for DFIs had a high rate of recurrences and mortality. Women, patients who underwent treatment with insulin, and those with eGFR <60 ml/min/1.73 m² had a higher risk of long-term mortality.

This study aimed to determine the prevalence of onychomycosis and interdigital tinea pedis in a cohort of Spanish patients with diabetes in whom onychomycosis was clinically suspected (n = 101). Samples from a first toenail scraping and the fourth toe clefts were subjected to potassium hydroxide direct vision and incubated in Sabouraud and dermatophyte test medium. Fifty-eight samples were also analyzed by a pathologist using periodic acid-Schiff staining and Calcofluor white direct fluorescence microscopy. Onychomycosis was only confirmed in 41 patients (40.6%). The most frequent aetiological agent was Trichophyton rubrum, isolated in 10 patients (36%), followed by Candida parapsilosis in 7 patients (25%). Tests on the fourth toe cleft samples were only positive in 11 patients (10.9%), and in all cases, onychomycosis was also diagnosed. Neuroischemic foot was the only significant variable associated with onychomycosis in the univariate analysis (P < .01). A positive result for mycosis in the fourth toe cleft was found in 11 cases (10.9%) and was associated with a history of myocardial infarction (P< .01; odds ratio [OR]: 84.2, confidence interval [CI]: 6.8-1036.4) and neuroischemic foot (P< .01; OR: 13.7, CI: 12.6-71.6) in the multivariate model. In conclusion, the prevalence of onychomycosis and tinea pedis in patients with diabetes in whom onychomycosis was clinically suspected was 40.6% and 10.9%, respectively. In addition, onychomycosis was not always associated with tinea pedis. These results show that clinical diagnosis has low accuracy in people with diabetes mellitus, and that diagnosis should not be based on clinical toenail characteristics alone.

Conservative surgery of diabetic foot osteomyelitis (DFO) in which bone infection is removed without amputation could minimize the biomechanical changes associated with foot surgery. We hypothesize that patients who undergo conservative surgery will have a longer survival time without recurrence of foot ulcers and further amputations than those who undergo any type of amputation to treat DFO. We assessed a retrospective cohort of 108 patients who underwent surgery for DFO from January 2011 to December 2012. Patients were followed-up until May 2020. Reulceration and reamputation-free survival times were plotted using the Kaplan–Meier method and were calculated from the date of first surgery to recurrence, new amputation, or end of the study. A stratified log rank was used to study differences among groups. Cumulative survival without recurrences at 1, 5, and 8 years was 95%, 36%, and 29%, respectively, in patients who underwent conservative surgery and 95%, 43%, and 30%, respectively, in those undergoing amputation. Cumulative survival without a new amputation at 1, 5, and 8 years was 100%, 80%, and 80%, respectively, in patients who underwent conservative surgery and 98%, 82%, and 69%, respectively, in those undergoing amputation. No differences were found regarding either recurrence (log rank, P = .98) or new amputations (log rank, P = .64). In conclusion, conservative surgery is as safe as amputation to arrest bone infection in the feet of patients with diabetes. Conservative surgery was not associated with a lower rate of recurrence and new amputations than those patients who underwent amputations.

Adult patients with human immunodeficiency virus (HIV) appear to be at high risk of cardiovascular disease (CVD). Peripheral arterial disease (PAD) is particularly concerning as it is associated with myocardial infarction and stroke. Nevertheless, the incidence of PAD is still unknown. The authors prospectively recruited HIV-infected patients from the outpatient clinic of the Department of Internal Medicine in our center. We assessed ankle-brachial index (ABI) using the VaSera system™ (Fukuda Denshi Co., Ltd). Patients were grouped into 3 ABI levels: an ABI ≤0.90 was considered abnormal and evidence of PAD, an ABI 1.0 to 1.40 was considered normal, and 0.91 to 0.99 was considered borderline. Cardiovascular risk factors were compared across all 3 levels of ABI and were analyzed using multivariate ordinal logistic regression. Eight hundred ninety-two patients were recruited. The mean age was 42.9 ± 10.0 years and 458 (51.4%) were males. There were 704, 149, and 39 patients in the normal, borderline, and abnormal ABI groups, respectively. The latter group of 39 patients was considered to have PAD, yielding a prevalence of 4.37% (95% confidence interval [CI] 3.21-5.93). Sex ratio, age, education levels, smoking rate, body mass index (BMI), blood pressure, prevalence of comorbidities with hypertension and coronary heart disease, median triglyceride level, reduced kidney function and HIV-1 RNA undetectable ratio, duration of HIV diagnosis, and duration on antiretroviral treatment were significantly different among 3 ABI subgroups. Independent risk factors associated with PAD were being female (odds ratio [OR]: 2.86; 95% CI: 1.94-4.22), being <30 years of age (OR: 4.66; 95% CI: 2.78-7.81), being overweight (BMI 25-25.9; OR: 0.39; 95% CI: 0.20-0.76), being obese (BMI: 30; OR: 3.53; 95% CI: 1.51-8.22), having a diastolic blood pressure ≥80 mmHg (OR: 0.50; 95% CI: 0.35-0.71), and having detectable HIV-1 RNA ≥20 copies/mL (OR: 1.85; 95% CI: 1.13-3.03). In conclusion, the prevalence of PAD in HIV-infected Thais was 4.37% in infected patients on therapy attending outpatient clinics. For this population, PAD appears to be relatively poorly correlated with traditional risk factors of CVD.

Reconstruction of soft tissue defects in the lower extremity due to different etiologies can be a challenging process for surgeons. Compelling reasons for reconstruction include the anatomy of the lower extremity, limited mobility of soft tissues especially the presence of bone, tendon, and neurovascular structures under the defect, and the exposed fixation materials make these defects more complicated. Local fasciocutaneous and muscle flaps are frequently used for the reconstruction of these defects. The patients in our study were with multiple comorbidities such as diabetes mellitus, hypertension, atherosclerosis, and peripheral vascular disease. In this study, with a clinic series consisting of 42 patients (29 male and 13 female), we present a reconstruction with a bipedicled flap as a safe, simple, and efficient reconstructive modality in the treatment of lower extremity soft tissue defects. Except for 1 total flap loss, all defects were successfully reconstructed without any major complications. When reconstruction is performed with a bipedicled flap, the main neurovascular structures are not damaged, free flap and other locoregional flaps can be used as a salvage protocol.

The aim of the research is to assess the benefit–harm of superabsorbent polymers wound dressings based on polyacrylate polymers (SAPs) compared with standard of care (SoC) dressing mix for patients with moderate-to-highly exuding hard-to-heal leg ulcers. The SoC dressings mix was composed of other superabsorbents in 29% of cases, antimicrobials 26%, foams 20%, alginates 5%, and other dressings 19% weighted according to their frequency. We have used the decision-analytic modeling method, Markov process, as an adequate analytical solution for medical prognosis. We have combined the systematic literature search to identify the most relevant inputs for the analysis, with available patient-level clinical data concerning benefits of superabsorbent to generate a robust prediction of patient-relevant outcomes, including healing rates and health-related quality of life. Besides, we have qualitatively described adverse events associated with those treatments. Our research indicates that SAPs when compared with SoC dressing mix in a patient with moderate-to-highly excluding leg ulcers are leading to an improved healing rate with an absolute risk difference of 2.20% in 6 months and a relative risk of 1.07 in favor of SAP dressings. The attributable fraction among those exposed to SAP dressings of 6.6%, meaning that 6.6% of the healed ulcers could be attributed to having had the SAP dressing treatment instead of the SoC dressing treatment. Besides, SAP dressings lead to improved quality of life measured as incremental quality-adjusted life weeks (QALWs) of 0.13 QALWs.

The aim of this study is to compare the efficacy of procalcitonin (PCT) and high-sensitive C-reactive protein (hsCRP) as diagnostic biomarkers in patients with diabetes and mild-to-moderate diabetic foot infections. A total of 119 patients (102 with type 2 diabetes and 17 with type 1 diabetes), of mean age 60.29 ± 10.05 years, divided into 3 groups—diabetic foot ulcer (DFU) with active infection (IDFU group, n = 41), DFU without clinical signs of infection (non-IDFU group, n = 35), and a control group with diabetes without DFU (n = 43). Infection severity was graded according to the International Working Group on the Diabetic Foot guideline—non-IDFU group as Grade 1, IDFU group as Grade 2 (n = 22), and Grade 3 (n = 19). Serum hsCRP was assessed by the immunoturbidimetric method and PCT by the enzyme chemiluminescence immunoassay (ECLIA) method. Levels of white blood cells (WBC) were assessed using the Medonic hematology analyzer and erythrocyte sedimentation rate (ESR) by the Westergren method. Serum hsCRP, WBC count, and ESR were significantly higher in the IDFU group as compared to non-IDFU and control groups, whereas PCT levels did not differ between the groups. hsCRP presented with higher sensitivity (80%), specificity (79%), area under the curve (AUC) 0.856, in comparison to PCT (sensitivity 63%, specificity 62%, AUC 0.617) for the presence of IDFU, as well as in the Grade 3 subgroup (84% sensitivity and specificity, AUC 0.911). The combined model of both markers did not present with better accuracy than using hsCRP alone. In conclusion, hsCRP appears to be a better diagnostic biomarker than PCT in the diagnosis of moderate foot ulcer infection. Both markers fail to distinguish mild infection.

Arginase expression has been recently shown to increase in numerous disease states like neurodegeneration, inflammation, and malignancies. Although it has been found to be functionally important in various disease pathologies, little is known about its role in wound healing. Here, we look at the expression of arginase and its isoforms in chronic non-healing wounds and also study the expression of nitric oxide synthase (NOS) and oxidative stress enzymes in them. Wound tissues and blood samples were collected at the time of index presentation and follow-up from 61 chronic non-healing wound cases. The expression patterns of arginase isoenzymes, NOS, superoxide dismutases (SOD), lactic acid dehydrogenase (LDH), and catalase were examined by using enzyme-linked immunosorbent assay, immunohistochemistry, and western blot analysis at the transcript and protein level. We reported a significant decrease of serum arginase levels in chronic nonhealing wounds in the progress of wound healing. Interestingly, tissue arginase levels were found to be increased with improved wound condition at follow-up. Tissue NOS, LDH, and catalase activity were also found to be increased with the progress of healing, whereas SOD levels were downregulated. Our findings reported increased expression at the transcript level of arginase-I and arginase-II in chronic non-healing wounds for the first time. In conclusion, we observed decreased serum arginase levels in completely healed patients as compared to non-healed cases. Our study findings support the hypothesis that inhibition of the activity of arginase delays wound healing. Arginase and iNOS may also find their place in the future as possible biomarkers for wound healing.

Acute wounds may require cleansing to reduce the risk of infection. Stabilized hypochlorous acid in acetic buffer (HOCl + buffer) is a novel wound irrigation solution with antimicrobial properties. We performed a first-in-man, prospective, open-label pilot study to document preliminary safety and performance in the treatment of acute wounds. The study enrolled 12 subjects scheduled for a split-skin graft transplantation, where the donor site was used as a model of an acute wound. The treatment time was 75 s, given on 6 occasions. A total of 7 adverse events were regarded as related to the treatment; all registered as pain during the procedure for 2 subjects. One subject had a wound infection at the donor site. The mean colony-forming unit (CFU) decreased by 41% after the treatment, and the mean epithelialization was 96% on both days 14 (standard deviation [SD] 8%) and 21 (SD 10%). The study provides preliminary support for the safety, well-tolerance, and efficacy of HOCl + buffer for acute wounds. The pain was frequent although resolved quickly. Excellent wound healing and satisfying antimicrobial properties were observed. A subsequent in vitro biofilm study also indicated good antimicrobial activity against Pseudomonas aeruginosa with a 96% mean reduction of CFU, when used for a treatment duration of 15 min (P < .0001), and a 50% decrease for Staphylococcus aureus (P = .1010). Future larger studies are needed to evaluate the safety and performance of HOCl + buffer in acute wounds, including the promising antimicrobial effect by prolonged treatment on bacterial biofilms.

The reconstruction of defects of the lateral malleolus involving the exposed fibular bone or tendon is challenging. This study aimed to evaluate the clinical application of the peroneal artery perforator flap with or without split-thickness skin grafting for soft tissue reconstruction of the bony defect of the lateral malleolus of the ankle joints. Reconstruction using a peroneal artery perforator flap with or without split-thickness skin grafting was performed for 15 patients (10 men, 5 women) between January 2007 and December 2018. The mean age was 53.7 years, and the mean size of the flaps was 40 cm². The flaps were elevated in the form of a perforator flap, and split-thickness skin grafting was performed over the flaps and adjoining raw areas. The flaps survived in all cases; however, partial necrosis was observed in 3 cases. In cases of small-sized defects of the lateral malleolus of the ankle joints where a flap is required for the exposed bone or tendon, reconstruction using the peroneal artery perforator flap is advantageous, since the morbidity rate of the donor site is low and soft tissue is reconstructed.

The main aims of this study were cross-cultural adaptation and reliability testing of an Arabic version of Foot Care Confidence Scale (FCCS), Foot Care Outcomes Expectations Scale (FCOES), Patient Interpretation of Neuropathy Scales (PINS), Neuropathy-specific Quality of Life Scales (NQOLS), and offloading-related Visual Analog Scales (VAS). Two phases of translation and reliability testing were conducted in Jordan. Phase 1 included 2 forward and backward translations with 2 panel consensuses (translators, clinicians, and experts). In Phase 2, Cronbach’s alpha (α) and intraclass correlation coefficient (ICC) were used to test the internal consistency and stability (test–retest) of the Arabic scales in a sample of a total of 90 Jordanian participants with diabetic foot ulcers. Phase 1 resulted in Arabic translation and cross-cultural adaptation of the study scales. Phase 2 resulted in acceptable internal consistency of the translated scales (α = 0.74-0.91), except for the PIN “self/practitioner blame” and “acute ulcer onset” scales (α = 0.57, 0.49, respectively). Test–retest results (ICC) were: FCCS (0.85); FCOES (0.78); PINS (0.043-0.85); NQOLS (0.76-0.90); and offloading-related VAS (0.43-0.90). This study showed evidence of cultural appropriateness and reliability of most of the translated scales, for possible future implementation for the Arabic population.

The treatment of the Cierny–Mader (C–M) type III–IV calcaneus osteomyelitis combining with the soft-tissue defect is sophisticated and difficult. The aim of this study is to introduce the application and availability of the modified distally based sural flap with an adipofascial extension to reconstruct these defects. We retrospectively reviewed the data of 37 patients with C–M type III–IV calcaneus osteomyelitis accompanied with soft-tissue defect between December 2004 and December 2019. A modified distally based sural flap with an adipofascial extension was conducted to reconstruct the defect. The patient's demographics, duration of the diseases, etiology, reconstruction outcomes, infection control rate, recurrence rate, amputation rate, and follow-up data were collected to evaluate the effectiveness and reliability of the modification. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot scale was applied to assess the function of the ankle and hindfoot. Thirty-four flaps survived uneventfully, 1 flap displayed marginal necrosis and 2 flaps (5.41%) developed partial necrosis. Using this modified flap alone or combining with some simple salvage methods reconstructed all of the defects successfully. The calcaneus osteomyelitis was cured successfully, and no recurrences were observed during the follow-up period. The AOFAS ankle and hindfoot scores were excellent in 27 patients and good in 8 patients. The distally based sural flap with an adipofacial extension is a simple and effective technique to reconstruct the calcaneus osteomyelitis combined with soft-tissue defect in 1 stage. Applications of the adipofacial extension to obliterate the dead space and the well-vascularized skin island to cover the defect are the guarantee of achieving good ankle and foot functions. However, this technique is not appropriate for the patients with calcaneum less than half weight-bearing area.

Wound is tissue damage that occurs in the skin. Helichrysum species (Altınotu) are rich in phenolic compounds used in traditional medicine for wound healing. The main component in their flower head (capitulum) is phenolic compounds. The present study investigates the proliferative, oxidative stress, and wound healing properties of the methanolic extract of Helichrysum plicatum subsp. pseudoplicatum capitulum on a human dermal fibroblast (HDF) cell line in this study. H plicatum subsp. pseudoplicatum capitulums were collected in Erzurum, Turkey (altitude 1950 m), dried, pulverized, and extracted with methanol. Firstly, total phenolic contents were determined and secondly, the proliferative effect, oxidative stress activities, and wound healing effects on HDF cells were evaluated by the cell proliferation kit (XTT) test, total antioxidant status (TAS), and total oxidant status (TOS) commercial kits, and the scratch experiment by taking microscopic images of the cells at 0, 12, 18, and 24 h, respectively. Total phenolic content was found to be 142.00 ± 0.73 mg gallic acid equivalent per gram (GAE/g) extract. The capitulum extract has a proliferative effect at 0.5 to 10 µg/mL concentrations according to the XTT test results. It was observed that TAS levels significantly increased in the plant extract at the concentration ranges 1 to 10 µg/mL (P < .01). About 1 to 5 µg/mL plant extract started to increase cell migration at the 12 h and significantly closed the wound area at the 24 h. At the doses between 1 to 5 μg/mL, it has the most substantial effect on both cell viability and antioxidant effect, and wound healing was found to be in this concentration range. These findings suggested that the H plicatum subsp. pseudoplicatum capitulum is a valuable source of phenolic content with important antioxidant activity at wound healing and it was concluded that the capitulum extract accelerates wound healing by increasing cell migration in low doses.

Impaired wound healing is a major concern in diabetic patients due to unregulated chronic hyperglycemia which further may lead to ulcer, gangrene, and its complications. The present study unveils the accelerative effect of aqueous Anthocephalus cadamba leaf extract on wound healing in diabetic rats. Diabetes was induced in 30 Sprague Dawley female rats by using streptozotocin (except control group I) at the dose of 60 mg/kg intraperitoneally. Diabetic rats were randomized in 3 groups viz. diabetic control group (II), diabetes + Kadam plant leaf extract group (III), and diabetes + 5% povidone–iodine solution group (IV). Surgically sterile wound of 1.77 cm² was created on the dorsal area of anaesthetized rats. The experimental parameters were assessed by hematobiochemical, histopathological, and western blot techniques. The A cadamba extract treatment group (III) (D + KPLE) showed a significant increase in the percentage of wound closure (82%) at day 21 as compared to the diabetic control group (42%), nondiabetic control group (I) (49%), and povidone–iodine treatment group (75%) group (IV). The findings of the present study suggest that the (D + KPLE) group (III) exhibited marked epithelial regeneration, neovascularization, collagen deposition, and fibroblast proliferation along with higher expression of vascular endothelial growth factor as compared to the diabetic control group (II), which was confirmed by histopathological examination and western blot analysis. The present study suggests that the topical application of aqueous A cadamba leaf extract exhibits accelerative wound-healing properties in diabetic rats.

Ulcers of mixed etiology are diagnostically elusive and challenging to treat, especially when rare conditions are superimposed. Pyoderma gangrenosum (PG) is an autoinflammatory, ulcerative skin disease that is difficult to diagnose. Diagnostic criteria exist but there are no specific clinical tests to identify it. We discuss a case of PG initially diagnosed as venous ulcer in the setting of peripheral artery disease, complicated by superinfection, refractory to standard wound care, multiple surgical debridements, revascularization, negative pressure therapy, and parenteral antibiotics. Findings differentiating PG from other wound etiologies are explored, with the aim of improving clinical recognition of this condition.

Necrotizing fasciitis is a surgically diagnosed infection of the deep soft tissues that results in high mortality. It is usually caused by aerobic and anaerobic bacteria and group A Streptococcus. Metallosis is characterized by the deposition of metal debris in the blood that causes metal poisoning and tissue damage. The abrasion of metal components that occurs after joint replacements causes metallosis, which may lead to severe complications. We report a rare case of metallosis-induced necrotizing fasciitis of the right thigh. Metallosis should be considered as a cause of necrotizing fasciitis if the patient has had a joint replacement surgery.

Pyoderma gangrenosum (PG) is a rare, immunological ulcerative, and necrotic inflammatory skin disease that can be easily misdiagnosed as cellulitis, abscess, diabetic foot ulcer, and other infectious diseases. Misdiagnosing PG leads to unnecessary surgical incision and debridement, which further exacerbates the lesion, ultimately leading to longer treatment periods and higher medical costs. Therefore, early and accurate diagnosis of PG is extremely important for its treatment. In particular, PG should be suspected in patients with inflammatory bowel disease.