Wound healing potential of topical bacteriophage therapy on diabetic cutaneous wounds

Chronic wounds that fail to heal are a common complication of diabetes mellitus and the most common precipitating reason for nontraumatic lower limb amputation. Unfortunately, the bacterial species that cause these infections are becoming more resistant to antibiotics, making them increasingly difficult to treat. We assessed the feasibility of combating chronic bacterial infections with a topically delivered bacteriophage cocktail in two animal models of diabetes mellitus. Microbiological, planimetric, and histological parameters were compared in debrided infected wounds with or without topical bacteriophage treatment. We determined that bacteriophage treatment effectively decreased bacterial colony counts and improved wound healing, as indicated by smaller epithelial and dermal gaps, in Staphylococcus aureus and Pseudomonas aeruginosa infections but was not as effective against Acinetobacter baumannii. Although the improvements were more significant in the rodent model than in the porcine model, our results suggest that topically administered bacteriophage treatment may be effective in resolving chronic infections, especially when applied in conjunction with wound debridement. These findings have important implications for the feasibility of using topical antimicrobial therapies to safely treat chronic infections in diabetes mellitus patients.     

Randomized placebo‐controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites

Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n = 34) showed significantly improved healing compared with placebo‐treated areas (day 1, p = 0.25; day 2, p = 0.011; day 3, p < 0.001; day 4, p < 0.001; day 5, p = 0.004; day 6, p = 0.008; day 7, p = 0.031). Positive effects were observed in terms of improved reepithelialization and fewer fibrin layers and blood crusts, whereas wound surroundings were always normal, independent of the type of treatment. Wound infection did not occur in any of the patients, and no relevant side effects were observed. Both types of treatment were well tolerated. The mechanisms contributing to these clinically observed effects should be further investigated.     

Fundamentals of randomized clinical trials in wound care: Reporting standards

In wound care research, available high‐level evidence according to the evidence pyramid is rare, and is threatened by a poor study design and reporting. Without comprehensive and transparent reporting, readers will not be able to assess the strengths and limitations of the research performed. Randomized clinical trials (RCTs) are universally acknowledged as the study design of choice for comparing treatment effects. To give high‐level evidence the appreciation it deserves in wound care, we propose a step‐by‐step reporting standard for comprehensive and transparent reporting of RCTs in wound care. Critical reporting issues (e.g., wound care terminology, blinding, predefined outcome measures, and a priori sample size calculation) and wound‐specific barriers (e.g., large diversity of etiologies and comorbidities of patients with wounds) that may prevent uniform implementation of reporting standards in wound care research are addressed in this article. The proposed reporting standards can be used as guidance for authors who write their RCT, as well as for peer reviewers of journals. Endorsement and application of these reporting standards may help achieve a higher standard of evidence and allow meta‐analysis of reported wound care data. The ultimate goal is to help wound care professionals make better decisions for their patients in clinical practice.     

Chronic venous leg ulcers are associated with high levels of metalloproteinases‐9 and neutrophil gelatinase‐associated lipocalin

Venous ulcers are related to dysfunctions in extracellular matrix. Both matrix metalloproteinases (MMP) and neutrophil gelatinase‐associated lipocalin (NGAL) could play a role in the healing process in patients with chronic venous ulcers. We evaluated the role of MMP‐9 and NGAL in the healing process in venous ulceration. We performed an open‐label, parallel groups, single clinical center study. Patients with chronic venous leg ulcers represented the test group (Group I), whereas patients without chronic ulcers represented the control group (Group II). In Group I plasma and wound fluid samples were collected at the time of admission, at the time of the surgery, and at the follow‐up, while ulcer tissues were taken at the time of the surgery. In Group II, plasma and wound fluid were collected at admission and at the time of the surgery, whereas skin tissues were collected at the time of the surgery. Enzyme‐linked immunosorbent assay test was used to evaluate the levels of MMP‐9 and NGAL in plasma and wound fluid, whereas Western blot analysis was performed to estimate the expression of MMP‐9 and NGAL in tissues. Enzyme‐linked immunosorbent assay tests revealed significantly higher levels of MMP‐9 and NGAL in both plasma and wound fluid of patients with ulcers compared to patients without ulcers (p < 0.01). Moreover, Western blot analysis documented an increased expression of MMP‐9 and NGAL in biopsy tissue of patients with ulcers compared to patients without ulcers (p < 0.01). In conclusion MMP‐9 and NGAL may correlate with the clinical course of venous ulcers.     

Topical application of the lectin Artin M accelerates wound healing in rat oral mucosa by enhancing TGF‐β and VEGF production

The lectin Artin M has been shown to accelerate the wound‐healing process. The aims of this study were to evaluate the effects of Artin M on wound healing in the palatal mucosa of rats and to investigate the effects of Artin M on transforming growth factor beta (TGF‐β) and vascular endothelial growth factor (VEGF) secretion by rat gingival fibroblasts. A surgical wound was created on the palatal mucosa of 72 rats divided into three groups according to treatment: C—Control (nontreated), A—Artin M gel, and V—Vehicle. Eight animals per group were sacrificed at 3, 5, and 7 days postsurgery for histology, immunohistochemistry and determination of the levels of cytokines, and growth factors. Gingival fibroblasts were incubated with 2.5 μg/mL of Artin M for 24, 48, and 72 hours. The expression of VEGF and TGF‐β was determined by enzyme‐linked immunosorbent assay. Histologically, at day 7, the Artin M group showed earlier reepithelialization, milder inflammatory infiltration, and increased collagen fiber formation, resulting in faster maturation of granular tissue than in the other groups (p < 0.05). Artin M–induced cell proliferation in vivo and promoted a greater expression of TGF‐β and VEGF in both experiments (p < 0.05). Artin M was effective in healing oral mucosa wounds in rats and was associated with increased TGF‐β and VEGF release, cell proliferation, reepithelialization, and collagen deposition and arrangement of fibers.     

Different Recurrence Pattern After Neoadjuvant Chemoradiotherapy Compared to Surgery Alone in Esophageal Cancer Patients

Purpose

To evaluate the rate and pattern of recurrences after neoadjuvant chemoradiotherapy (CRT) in esophageal cancer patients.

Methods

We described survival and differences in recurrences from a single center between neoadjuvant CRT (carboplatin/paclitaxel and 41.4 Gy) and surgery alone for the period 2000–2011. To reduce bias, we performed a propensity score matched analysis.

Results

A total of 204 patients were analyzed, 75 treated with neoadjuvant CRT and 129 with surgery alone. The pathologic response to neoadjuvant CRT was 69 % with a complete response rate of 25 %. After matching, baseline characteristics between the groups (both n = 75) were equally distributed. The 3- and 5-year disease-free survival was 53 and 42 % in the neoadjuvant CRT group compared with 24 and 18 % in the surgery-alone group (P = 0.011). After 3 and 5 years’ CRT, patients had an estimated locoregional recurrence-free survival of 83 and 73 % compared with 52 and 49 % in the surgery-alone group (P = 0.015). The distant recurrence-free survival was comparable in both groups. Locoregional recurrences were located less in the paraesophageal lymph nodes in the CRT group than in the surgery-alone group, 9 versus 21 %, respectively (P = 0.041). With respect to differences in distant recurrences, we observed more skeletal recurrences in the surgery-alone group compared to CRT, 12 versus 1 % (P = 0.009).

Conclusions

The neoadjuvant CRT regimen we used offers a significant improvement in outcome, with a different recurrence pattern compared with surgery alone. This effect is probably due to both the pathologic complete response and eradication of micrometastases in CRT group.     

Dalteparin Vs Low-Dose Unfractionated Heparin for Prophylaxis Against Clinically Evident Venous Thromboembolism in Acute Traumatic Spinal Cord Injury: A Retrospective Cohort Study

Background: When venous thromboembolism (VTE) includes deep-vein thrombosis (DVT) and pulmonary embolism (PE), patients with acute traumatic spinal cord injury (SCI) have the highest incidence of VTE among all hospitalized groups, with PE the third most common cause of death. Although low-molecular-weight heparin (LMWH) outperforms low-dose unfractionated heparin (LDUH) in other patient populations, the evidence in SCI remains less robust.

Objective: To determine whether the efficacy for LMWH shown in previous SCI surveillance studies (eg, routine Doppler ultrasound) would translate into real-world effectiveness in which only clinically evident VTE is investigated (ie, after symptoms or signs present).

Methods: A retrospective cohort study was conducted of 90 patients receiving LMWH dalteparin (5,000 U daily) or LDUH (5,000 U twice daily) for VTE prophylaxis after acute traumatic SCI. The incidence of radiographically confirmed VTE was primarily analyzed, and secondary outcomes included complications of bleeding and heparin-induced thrombocytopenia.

Results: There was no statistically significant association (p = 0.7054) between the incidence of VTE (7.78% overall) and the type of prophylaxis received (LDUH 3/47 vs dalteparin 4/43). There was no significant differences in complications, location of VTE, and incidence of fatal PE. Paraplegia (as opposed to tetraplegia) was the only risk factor identified for VTE.

Conclusions: There continues to be an absence of definitive evidence for dalteparin (or other LMWH) over LDUH as the choice for VTE prophylaxis in patients with SCI. Novel approaches to VTE prophylaxis are urgently required for this population, whose risk of fatal PE has not decreased over the last 25 years.     

The Effect of Body Weight-Supported Treadmill Training on Muscle Morphology in an Individual With Chronic,Motor- Complete Spinal Cord Injury: A Case Study

Abstract

Objective: The purpose of this pilot study was to examine the effects of 4 months of thrice-weekly body weight-supported treadmill training (BWSTT) on skeletal muscle morphology in a woman (age 27 y) with chronic, motor-complete (ASIA B) spinal cord injury (SCI).

Methods: The participant performed passive thrice-weekly BWSTT for 4 months (48 total sessions) with manual assistance from therapists. Muscle biopsies of the vastus lateralis were taken prior to the beginning of the training program as well as following the completion of 4 months of training. Histochemical analysis was utilized to evaluate changes in muscle fiber size and type following training.

Results: At baseline, vastus lateralis muscle biopsies showed evidence of fiber atrophy and fiber type redistribution typical of persons with SCI, with mean fiber areas (and % distributions) of type I, type I la and type llx fibers being 3474nm2 (1.3%), 3146nm2 (30.8%) and 1284^im2 (68.0%), respectively. Following training, there were increases in treadmill walking speed (pre: 1.0km/h; post: 2.5km/h) and distance walked/session (pre: 500m; post: 1875m). Vastus lateralis mean fiber area increased by 27.1% and type I fiber % distribution increased to 24.6%, whereas type I la and type llx fiber % distributions both decreased following training.

Conclusion: These data indicate that 4 months of thrice-weekly BWSTT improved muscle morphology in an individual with chronic, motor-complete SCI.