Effects of low‐frequency pulsed electromagnetic fields on plateau frostbite healing in rats

Plateau frostbite (PF) treatments have remained a clinical challenge because this condition injures tissues in deep layers and affected tissues exhibit unique pathological characteristics. For instance, low‐frequency pulsed electromagnetic field (PEMF) can affect tissue restoration and penetrate tissues. Therefore, the effect of PEMF on PF healing should be investigated. This study aimed to evaluate the effects of low‐frequency PEMF on PF healing systematically. Ninety‐six Sprague‐Dawley rats were randomly and equally divided into three groups: normal control, partial thickness plateau frostbite (PTPF), and PTPF with low‐frequency PEMF exposure (PTPF + PEMF). PTPF wounds were induced in the dorsum of the rats. The PTPF + PEMF group was exposed to low‐frequency PEMF daily. During PF healing, wound microcirculation in each group was monitored through contrast ultrasonography. Wound appearance, histological observation, and wound tensile strength were also evaluated. Results showed that the rate of the microcirculation restoration of the PTPF + PEMF group was nearly 25% faster than that of the PTPF group, and wound appearance suggested that the healing of the PTPF group was slower than that of the PTPF + PEMF group. Histological observation revealed that PEMF accelerated the growth of different deep tissues, as confirmed by tensile strength examination. Low‐frequency PEMF could penetrate PF tissues, promote their restoration, and provide a beneficial effect on PF healing. Therefore, this technique may be a potential alternative to treat PF.     

Defining a new diagnostic assessment parameter for wound care: Elevated protease activity,an indicator of nonhealing,for targeted protease‐modulating treatment

It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil‐derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2–4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies.     

A systematic review of low‐level light therapy for treatment of diabetic foot ulcer

Diabetes mellitus (DM) is a significant international health concern affecting more than 387 million individuals. A diabetic person has a 25% lifetime risk of developing a diabetic foot ulcer (DFU), leading to limb amputation in up to one in six DFU patients. Low‐level light therapy (LLLT) uses low‐power lasers or light‐emitting diodes to alter cellular function and molecular pathways, and may be a promising treatment for DFU. The goal of this systematic review is to examine whether the clinical use of LLLT is effective in the healing of DFU at 12 and 20 weeks in comparison with the standard of care, and to provide evidence‐based recommendation and future clinical guidelines for the treatment of DFU using LLLT. On September 30, 2015, we searched PubMed, EMBASE, CINAHL, and Web of Science databases using the following terms: “diabetic foot” AND “low level light therapy,” OR “light emitting diode,” OR “phototherapy,” OR “laser.” The relevant articles that met the following criteria were selected for inclusion: randomized control trials (RCTs) that investigated the use of LLLT for treatment of DFU. Four RCTs involving 131 participants were suitable for inclusion based upon our criteria. The clinical trials used sham irriadiation, low dose, or nontherapeutic LLLT as placebo or control in comparison to LLLT. The endpoints included ulcer size and time to complete healing with follow‐up ranging from 2 to 16 weeks. Each article was assigned a level of evidence (LOE) and graded according to the Oxford Center for Evidence‐based Medicine Levels of Evidence Grades of Recommendation criteria. Limitations of reviewed RCTs include a small sample size (N < 100), unclear allocation concealment, lack of screening phase to exclude rapid healers, unclear inclusion/exclusion criteria, short (<30 days) follow‐up period, and unclear treatment settings (wavelength and treatment time). However, all reviewed RCTs demonstrated therapeutic outcomes with no adverse events using LLLT for treatment of DFU. This systematic review reports that LLLT has significant potential to become a portable, minimally invasive, easy‐to‐use, and cost effective modality for treatment of DFU. To enthusiastically recommend LLLT for treatment of DFU, additional studies with comparable laser parameters, screening period to exclude rapid healers, larger sample sizes and longer follow‐up periods are required. We envision future stringent RCTs may validate LLLT for treatment of DFU. Systematic review registration number: PROSPERO CRD42015029825.     

False‐positive Extra‐Mammary Findings in Breast MRI: Another Cause for Concern

Breast magnetic resonance imaging (MRI) has been repeatedly shown to have a high false‐positive rate for additional findings in the breast resulting in additional breast imaging and biopsies. We hypothesize that breast MRI is also associated with a high rate of false‐positive findings outside of the breast requiring additional evaluation, interventions, and delays in treatment. We performed a retrospective review of all breast MRIs performed on breast cancer patients in 2010 at a single institution. MRI reports were analyzed for extra‐mammary findings. The timing and yield of the additional procedures was also analyzed. Three hundred and twenty‐seven breast cancer patients (average age = 53.53 ± 11.08 years) had a breast MRI. Incidental, extra‐mammary findings were reported in 35/327 patients (10.7%) with a total of 38 incidental findings. The extra‐mammary findings were located in the liver (n = 21, 60.0%), thoracic cavity (n = 12, 34.3%), kidneys (n = 1, 2.9%), musculoskeletal system (n = 3, 8.6%), and neck (n = 1, 2.9%). Eighteen of the 35 patients (51.4%) received additional radiographic imaging, 3 (8.6%) received additional laboratory testing, 2 (5.7%) received additional physician referrals and 2 (5.7%) received a biopsy of the finding. The average time to additional procedures in these patients was 14.5 days. None of the incidental, extra‐mammary findings were associated with breast cancer or other malignancy. Breast MRI was associated with a high rate (10.7%) of extra‐mammary findings, which led to costly additional imaging studies, referrals, and tests. These findings were not associated with breast cancer or other malignancies. Extra‐mammary findings highlight an unrecognized adverse consequence of breast MRI.     

Digital Breast Tomosynthesis: A New Diagnostic Method for Mass‐Like Lesions in Dense Breasts

To compare the rates and accuracy of digital breast tomosynthesis (DBT) and 2D digital mammography (DM) for detecting and diagnosing mass‐like lesions in dense breasts. Mediolateral and craniocaudal images taken with DBT (affected breast) and DM (both breasts) of the dense breasts of 631 women were assessed independently using Breast Imaging Reporting and Data System (BI‐RADS) scores. Images were compared for detection and diagnostic accuracy for masses; sensitivity and specificity of diagnosis; false‐negative and recall rates; and clarity of display, particularly of margins and spicules. Histopathology was conducted via surgical biopsies of all patients. The detection and diagnostic accuracy rates of DBT images (84.3% and 82.3%, respectively) were significantly higher than that of DM (77.3% and 73.4%; p < 0.01, both). The sensitivity and specificity of DBT (68.1% and 95.2%) were higher than that of DM (58.8% and 86.7%), whereas the recall rate of DBT was lower (3.6% cf. 9.8%). The number of cases of benign circumscribed masses and malignant spiculated masses detected by DBT (172 and 182) was significantly higher than the number detected through DM (75 and 115; p < 0.01, both). Radiologists assigned higher BI‐RADS scores for probability of malignancy to DBT images than DM, to lesions proved malignant (p = 0.025); for benign cases, the methods were comparable (p = 0.065). Compared with DM, DBT yielded significantly higher rates of detection and diagnostic accuracy for benign and malignant masses, with greater sensitivity and specificity and lower recall rates. In addition, DBT images facilitated analysis of margins, and the rate of accuracy for judgments of malignancy probability was higher, as proved on biopsy.