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AnteayerInternational Wound Journal

The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo


Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high‐voltage and high‐frequency power supply. Eight‐week‐old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low‐dose group), and 180s' CAP (high‐dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound‐healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low‐dose group and high‐dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL‐6, tumour necrosis factor‐α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor‐β in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound‐healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.

The heel amelanotic melanoma, a rare subtype of skin cancer misdiagnosed as foot ulcer: A case report


Amelanotic melanoma (AM) of the heel is a very rare subtype of malignant melanoma in which the tumour cells, unlike other types of melanoma, are characterised by little or no melanin pigmentation. AM resembles many benign dermatological complications that often lead to late diagnosis of lesions, poor prognosis, and occasionally misdiagnosis at an early stage of the disease. We report a case of a 73‐year‐old man with a heel ulcer who was admitted to Al‐Zahra Hospital (Isfahan, Iran). Chronic osteomyelitis was considered the primary diagnosis, and several courses of antibiotics were prescribed for the patient. The ulcer failed to improve after 9 months' of therapy, and because of an increase in the size of the ulcer and the growth of two tumours in the right heel, a biopsy of the lesion was conducted. The pathology report confirmed invasive AM. The present report emphasises the necessity to biopsy all skin lesions, even with low clinical significance, to avoid wrong subsequent treatments, prevent a delay in diagnosis, reduce misdiagnosis, and improve the survival rate of patients.

Clinical and economic burden of wound care in the tropics: a 5‐year institutional population health review


The aim of this study is to evaluate the clinical and economic burden of wound care in the Tropics via a 5‐year institutional population health review. Within our data analysis, wounds are broadly classified into neuro‐ischaemic ulcers (NIUs), venous leg ulcers (VLUs), pressure injuries (PIs), and surgical site infections (SSIs). Between 2013 and 2017, there were a total of 56 583 wound‐related inpatient admissions for 41 461 patients, with a 95.1% increase in wound episodes per 1000 inpatient admissions over this period (142 and 277 wound episodes per 1000 inpatient admissions in 2013 and 2017, respectively). In 2017, the average length of stay for each wound episode was 17.7 days, which was 2.4 times that of an average acute admission at our institution. The average gross charge per wound episode was USD $12 967. Among the 12 218 patients with 16 674 wound episodes in 2017, 71.5% were more than 65 years of age with an average Charlson Comorbidity Index (CCI) of 7.2. Half (51.9%) were moderately or severely frail, while 41.3% had two or more wound‐related admission episodes. In 2017, within our healthcare cluster, the gross healthcare costs for all inpatient wound episodes stand at USD $216 million within hospital care and USD $596 000 within primary care. Most NIU patients (97.2%) had diabetes and they had the most comorbidities (average CCI 8.4) and were the frailest group of patients (44.9% severely frail). The majority of the VLU disease burden was at the specialist outpatient setting, with the average 1‐year VLU recurrence rate at 52.5% and median time between healing and recurrence at 9.5 months. PI patients were the oldest (86.5% more than 65 years‐old), constituted the largest cohort of patients with 3874 patients at an incidence of 64.6 per 1000 admissions in 2017, and have a 1‐year all‐cause mortality rate of 14.3%. For SSI patients, there was a 125% increase of 14.2 SSI wound episodes per 1000 inpatient admissions in 2013 to 32.0 in 2017, and a 413% increase in wound‐related 30‐day re‐admissions, from 40 in 2013 (4.1% of all surgeries) to 205 (8.3% of all surgeries) in 2017. The estimated gross healthcare cost per patient ranges from USD $15789–17 761 across the wound categories. Similar to global data, there is a significant and rising trend in the clinical and economic burden of wound care in Tropics.

Evaluation of mortality risk factors in diabetic foot infections


Identifying risk factors for mortality is crucial in the management of diabetic foot syndrome. We aimed to evaluate risk factors for mortality in patients with diabetic foot infection (DFI). A retrospective chart review was conducted on 401 patients from 2010 through 2019. Our primary endpoint was in‐hospital mortality. Patients were divided into two groups according to the outcome (survival or death). Clinical data were compared between the two groups statistically. A total of 401 patients were enrolled in the study, 280 (69.8%) of them were male and the mean age was 59.6 ± 11.1 years. The mean follow‐up period was 23.7 ± 22.9 months. In‐hospital mortality rate was 3%. Univariate analysis indicated that ischaemic wound (P = .023), hindfoot infection (P = .038), whole foot infection (P = .010), peripheral arterial disease (P = .024), high leucocyte levels (>12 040 K/μL) (P = .001), high thrombocyte levels (>378 000 K/μL) (P < 0.001), high C‐reactive protein levels (>8.81 mg/dL) (P = .022), and polymicrobial growth in deep tissue culture (P = .041) were significant parameters in predicting mortality. In multivariate analysis, peripheral arterial disease (odds ratio [OR]: 13.430, 95% confidence interval [Cl]: 1.129‐59.692; P = .040), high thrombocyte levels (OR: 1.000, 95% Cl: 1.000‐1.000; P = .022), and polymicrobial growth in deep tissue culture (OR: 7.790, 95% Cl: 1.592‐38.118; P = .011) were independent risk factors for mortality. In conclusion, peripheral arterial disease, high thrombocyte levels, and polymicrobial growth in deep tissue culture were independent risk factors for mortality in DFI.

Models for predicting skin tears: A comparison


A recently published model that predicted the risk of skin tears in older adults was compared with seven additional published models. Four models were excluded because of limitations in research design. Four models were compared for their relative predictive performance and accuracy using sensitivity, specificity, and the area under the curve (AUC), which involved using receiver‐operating characteristic analysis. The predictive ability of the skin tear models differed with the AUC ranging between 0.673 and 0.854. Based on the predictive ability, the selection of models could lead to different clinical decisions and health outcomes. The model, which had been adjusted for potential confounders consisted of five variables (male gender, history of skin tears, history of falls, clinical skin manifestations of elastosis, and purpura), was found to be the most parsimonious for predicting skin tears in older adults (AUC 0.854; 81.7% sensitivity; 81.4% specificity). Effective models serve as important clinical tools for identifying older individuals at risk of skin tears and can better direct more timely and targeted prevention strategies that improve health outcomes and reduce health care expenditure.

Comparison of platelet‐rich plasma gel in the care of the pressure ulcers with the dressing with serum physiology in terms of healing process and dressing costs


This research was carried out with the aim of comparing the effects of platelet‐rich plasma (PRP) gel and gas dressing with serum physiologic applied to stage II pressure ulcer in coccyx of patients for 2 months on healing process and dressing costs. This prospective randomised controlled experimental study was conducted with 60 patients hospitalised in the palliative care unit after surgery. The experimental group (n = 30) was dressed with platelet‐rich plasma gel. The control group (n = 30) was treated with serum physiologic dressing. At the end of the 20th observation of the patients in the experimental group, it was found that the mean scores of area, exudate, and tissue type in pressure sores decreased statistically (P < .001). In the control group, no significant difference was found between the mean PUSH score at the end of the 20th observation (P > .05). The study showed that PRP gel had a positive effect on healing of stage II pressure ulcers with platelet‐rich plasma gel dressings. In addition, when evaluated in the long term, it was concluded that platelet‐rich plasma gel is easily accessible and less costly than serum physiological dressing.

Healing hand ulcers caused by focal spasticity


Spasticity is a common manifestation of many upper motor neuron lesions such as stroke, traumatic brain injury, and multiple sclerosis. In some cases, spastic fingers in the hand press hard into the palm, resulting in skin breakdown and atypical pressure ulcerations. We treated 10 such patients living in the nursing homes with long‐standing treatment‐resistant hand ulcers in our spasticity clinic first, with Botulinum toxin A (BoNTA) injection into the spastic muscles followed by dressing, splinting, and hand therapy. These ulcers failed to respond to standard treatment, causing significant pain, offensive smell, increased carer burden, and difficulty in maintaining hygiene as hands could barely be opened for dressing and therapy. We noted complete healing of ulcers with significant improvement in the following outcome measures—Modified Ashworth Scale for spasticity, Visual Analog Scale for pain, pressure ulcer grading for the ulcers, Fingertip to Palm distance for hand opening, Carer Burden Scale, and in the Goal Attainment Scale pre, 4 weeks, and 3 months postinjection with P values of .003, .003, .004, .005, .004, and .004, respectively. Reducing spasticity with BoNTA should be the first step in treating hand ulcerations caused by focal spasticity, followed by dressing, splinting, and hand therapy.

Understanding factors influencing venous leg ulcer guideline implementation in Australian primary care


The aim of this study was to gain a better understanding of the venous leg ulcer (VLU) management in primary health care settings located in Melbourne metropolitan and rural Victoria, Australia. We explored health professionals' perspective on the use of the Australian and New Zealand Venous Leg Ulcer Clinical Practice Guideline (VLU CPG) to identify the main challenges of VLU CPG uptake in clinical practice. We conducted semi‐structured interviews with 15 general practitioners (GPs) and 20 practice nurses (PNs), including two Aboriginal health nurses. The Theoretical Domains Framework guided data collection and analysis. Data were analysed using a theory‐driven analysis. We found a lack of awareness of the VLU CPGs, which resulted in suboptimal knowledge and limited adherence to evidence‐based recommendations. Environmental factors, such as busy nature of clinical environment and absence of handheld Doppler ultrasound, as well as social and professional identity factors, such as reliance on previous experience and colleague's advice, influenced the uptake of the VLU CPGs in primary care. Findings of this study will inform development of interventions to increase the uptake of the VLU CPG in primary care settings and to reduce the evidence‐practice gap in VLU management by health professionals.

World Union of Wound Healing Societies Meeting, 2020

International Wound Journal, Volume 17, Issue 2, Page 241-241, April 2020.


International Wound Journal, Volume 17, Issue 2, Page 523-523, April 2020.

Human amniotic membrane allograft, a novel treatment for chronic diabetic foot ulcers: A systematic review and meta‐analysis of randomised controlled trials


To evaluate the efficacy and safety of human amniotic membrane (HAM) allograft in treating chronic diabetic foot ulcers (DFUs), a comprehensive search of randomised controlled trials in MEDLINE, EMBASE, PubMed, CENTRAL and Web of Science was conducted to December 7, 2019. Two reviewers independently screened the studies, extracted data, and evaluated the quality of studies. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. Statistical analyses were performed using RevMan 5.3. We identified 257 articles, of which 7 articles (465 participants) were included in the meta‐analysis. The proportion of complete wound healing in HAM plus standard of care (SOC) group was 3.88 times as high as that in SOC alone (RR: 3.88 [95% CI: 2.34, 6.44]) at 6 weeks, and 2.01 times at 12 weeks (RR: 2.01 [95%CI: 1.45, 2.77]). The intervention group had a significantly shorter time to complete healing (MD: −30.33 days, [95% CI: −37.95, −22.72]). The number needed to treat within 6 weeks was 2.3 ([95% CI: 1.8, 3.1]). No significant difference was shown in adverse events. Results were consistent in a sensitivity analysis. Hence, HAM plus SOC is effective and safe in treating chronic DFUs.

Deep sternal wound infection following cardiac surgery: A comparison of the monolateral with the bilateral pectoralis major flaps


Deep sternal wound infections are a serious complication following sternotomy for cardiothoracic surgery. “Conventional” treatment provides debridement and secondary closure or closed catheter irrigation. The combination of the Negative Pressure Therapy with flap coverages is an accepted technique and one or both Pectoralis Major muscles could be chosen. A multistep protocol was adopted. One hundred and sixty seven patients were treated with the combination of Negative Pressure Therapy with the Pectoralis Major muscle flap: 86 monolateral flap and 81 bilateral flap reconstruction. The main complications (hematoma, seroma, dehiscence, and re‐infection), the need for re‐intervention, mortality rates, Intensive Care Unit, and hospitalisation time were assessed. The mono‐pectoralis group had fewer complications and need for revision, with a shorter hospital stay. A statistically significant difference emerged for the hematoma rate (P = .0079). Monolateral flap should to be preferred because with the same coverage effectiveness, it guarantees the saving of controlateral muscle with its functionality and the possibility of its use in case of failure. Furthermore, as the technique is less invasive, it can be reserved for more fragile patients.

High body mass index is a strong predictor of intraoperative acquired pressure injury in spinal surgery patients when prophylactic film dressings are applied: A retrospective analysis prior to the BOSS Trial


We reported the efficacy of soft silicone multilayered foam dressings in preventing intraoperatively acquired pressure injuries (IAPIs) in the prone position using a Relton‐Hall frame (BOSS trial). The aim of this study was to clarify the incidence and extract the risk factors for IAPIs in cases in which polyurethane film dressing was used against IAPIs before the BOSS trial period. This study conducted as a retrospective dual‐center cohort study between August 2014 and Jun 2015 using the medical records in the operating room. The incidence of IAPIs that developed within 24 hours after surgery was 7.1% (7/99). The multivariate logistic regression analysis revealed that body mass index (BMI) (P = .0016, odds ratio [OR]: 1.22, 95% confidence interval (CI) 1.08‐1.4) and length of surgery (P < .0001, OR 2.47, 95% CI 1.86‐3.51) were independently associated with the development of IAPIs. Since high BMI was not extracted in BOSS trial, we conclude that the application of soft silicone multilayer foam dressings is important for preventing the development of IAPIs in patients with high BMI values.

Efficacy of topical silicone gel in scar management: A systematic review and meta‐analysis of randomised controlled trials


To assess the efficacy of topical silicone gel in the management of scars, we conducted this meta‐analysis. The systematic search was performed on PubMed, Web of Science and Embase, and six randomised controlled trials with a total of 375 patients were involved. The outcome data of Vancouver Scar Scale were extracted from the studies and their effect sizes were calculated using Review Manager 5.3. As a result, topical silicone gel significantly reduced pigmentation, height, and pliability scores postoperatively compared with placebos or no treatment (Pigmentation: standard mean difference [SMD] = −0.55 [−0.83 to –0.26], P = .0002; Height: SMD = −0.73 [−1.02 to –0.44], P < .00001; Pliability: SMD = −0.49 [−0.95 to –0.03], P = .04). Topical silicone gel and silicone gel sheet were comparably effective (P > .05). The performance of topical silicone gel and other non‐silicone topical treatment was also similar (P > .05). In summary, topical silicone gel was effective in post‐operative scar prevention.

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International Wound Journal, Volume 17, Issue 2, Page 242-244, April 2020.

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International Wound Journal, Volume 17, Issue 2, Page 237-240, April 2020.

Factors affecting postmusculoskeletal tumour surgery wound problem treatment with negative pressure wound therapy


The aim of the study is to investigate the risk factors identified in literature that have been associated with prolonged Negative Pressure Wound Therapy (NPWT). Our study included patients who developed local wound problems after bone or soft tissue sarcoma surgery with negative margin at our clinic between 2012 and 2018 and treated with NPWT. All patients were followed up of at least 6 months. Sex, albumin level, skin infiltration, type of wound problem, postoperative intensive care unit (ICU) requirement, and intraoperative blood loss were found to be influential factors on NPWT > 10 sessions. We conclude that treatment may be prolonged and the necessary precautions need to be taken in patients with an impaired preoperative nutritional condition, with intraoperative high amount of blood loss, and with long postoperative stays in the ICU as well as if the underlying cause for wound problem is an infection.

Surgical site infection following operative treatment of open fracture: Incidence and prognostic risk factors


Considering the high incidence of postoperative complications of open fracture, management of this injury is an intractable challenge for orthopaedist, and surgical site infection (SSI) is the devastate one. Screening for high‐risk patients and target them with appropriate interventions is important in clinical practice. The aim of this study was to identify modifiable factors that were associated with SSI following operative treatment of open fractures. This retrospective, multicentre study was conducted at three hospitals. A total of 2692 patients with complete data were recruited between June 2015 and July 2018. Demographic characteristics, operation relative variables, additional comorbidities, and biochemical indexes were extracted and analysed. Receiver operating characteristic analysis was performed to detect the optimum cut‐off value for some variables. Univariate and multivariate logistic analysis models were performed, respectively, to identify the independent risk factors of SSI. The overall incidence of SSI was 18.6%, with 17.0% and 1.6% for superficial and deep infection, respectively. Results of univariate and multivariate analyses showed the following: fracture type, surgical duration > 122 minutes, anaesthesia time > 130 minutes, intraoperative body temperature < 36.4°C, blood glucose (GLU) > 100 mg/dL, blood platelet (PLT) < 288 × 109, and white blood cells (WBC) > 9.4 × 109 were independent risk factors of postoperative wound infection following operative treatment of open fractures. Six modifiable factors such as surgical duration > 122 minutes, anaesthesia time > 130 minutes, intraoperative body temperature < 36.4°C, GLU > 100 mg/dL, PLT < 288 × 109, and WBC > 9.4 × 109 play an important role in the prevention of SSI, and these factors should be optimized perioperatively.

Influence of human wound exudate on the bactericidal efficacy of antiseptic agents in quantitative suspension tests on the basis of European Standards (DIN EN 13727)


The antimicrobial efficacy of antiseptics used in wound management is tested in vitro under standardised conditions according to DIN EN 13727, with albumin and sheep erythrocytes used as organic challenge. However, these testing conditions do not adequately simulate the wound bed environment. Thus, the aim of this study was to compare the efficacy of different antiseptics such as octenidine dihydrochloride (OCT), chlorhexidine digluconate (CHX), polyhexamethylene biguanide (PHMB), and povidone‐iodine under challenge with human wound exudate instead of standardised organic load in an in vitro setting according to DIN EN 13727. Moreover, protein contents, pH, and temperature were compared with standardised testing conditions. The tested antiseptic agents were reduced to different extents based on their bactericidal efficacy, when challenged with human wound exudate compared with standardised conditions. Overall, 0.10% OCT showed the highest effects reaching full efficacy after 30 seconds. CHX and PHMB were the least efficient. Next to the protein content, other components of wound exudate, such as the microflora, seem to influence the efficacy of antiseptics. In summary, the optimisation of in vitro testing conditions in future applications, to more adequately simulate the wound bed environment, will allow a more realistic picture on the potential performance of antiseptics in clinical practice.