Handheld fluorescence imaging device detects subclinical wound infection in an asymptomatic patient with chronic diabetic foot ulcer: a case report.

Chronic wounds are a significant burden to global patient and health care infrastructures, and there is a need for better methods of early wound diagnosis and treatment. Traditional diagnosis of chronic wound infection by pathogenic bacteria, using clinical signs and symptoms, is based on visual inspection under white light and microbiological sampling (e.g. swabbing and/or biopsy) of the wound, which are subjective and suboptimal. Diagnosing microbial infection based on traditional clinical signs and symptoms in wounds of asymptomatic patients is especially challenging at the bedside. Bacteria are invisible to the unaided eye and wound sampling for diagnostic testing can cause unacceptable delays in diagnosis and treatment. To address this problem, we developed a new prototype handheld, portable fluorescence imaging device that enables non-contact, real-time, high-resolution visualisation of pathogenic bacteria and tissues in wounds. Herein, we report the clinical use of this imaging device in detecting subsurface heavy bacterial load and subclinical local infection in an asymptomatic 50-year-old patient with a non-healing diabetic foot ulcer.

Impact of Pretreatment Interstitial Lung Disease on Radiation Pneumonitis and Survival in Patients Treated With Lung Stereotactic Body Radiation Therapy (SBRT).

INTRODUCTION: The purpose of this study was to determine the impact of interstitial lung disease (ILD) on radiation pneumonitis (RP) and overall survival (OS) in lung stereotactic body radiation therapy (SBRT). METHODS: Patients treated with lung SBRT from 2004 to 2015 were included. Pretreatment computed tomography scans were reviewed and classified for interstitial changes by thoracic radiologists using American Thoracic Society guidelines and Washko and Kazerooni scores. RP was scored prospectively using Common Terminology Criteria for Adverse Events, version 3.0. Pretreatment imaging characteristics, clinical variables, and dosimetry were assessed by univariate (UVA) and multivariate analysis (MVA). OS was assessed by the log-rank test, and the impact of ILD on OS was assessed by Cox regression. RESULTS: Of the 537 patients assessed, 39 had interstitial changes (13 usual interstitial pneumonia [UIP], 24 possible UIP, and 2 inconsistent with UIP). RP was significantly higher in patients with ILD than in patients without ILD (grade ≥ 2, 20.5% vs. 5.8%; P < .01; grade ≥ 3, 10.3% vs. 1.0%; P < .01). Two of 3 grade 5 RP had imaging features of ILD. On UVA, ILD, Washko score, lung parameters performance status, and dose were significant predictors of grade ≥ 2 RP. On MVA, ILD (odds ratio, 5.81; 95% confidence interval, 2.28-14.83; P < .01) and mean lung dose (odds ratio, 1.40; 95% confidence interval, 1.14-1.71; P < .01) were predictors of RP. ILD did not significantly affect OS on UVA or MVA. Median survival was 27.4 months in the ILD cohort and 34.8 in the ILD-negative cohort (P = .17). DISCUSSION: ILD is a significant risk factor for RP in patients treated with lung SBRT. Computed tomography scans should be reviewed for evidence of ILD prior to SBRT.

Survival Impact of Cardiac Dose Following Lung Stereotactic Body Radiotherapy.

INTRODUCTION: The purpose of this study was to determine the impact of radiation dose to substructures of the heart in lung stereotactic body radiotherapy (SBRT) patients on non-cancer-related deaths. METHODS: Patients treated with lung SBRT at a single institution from 2005 to 2013 were included. The heart and its substructures were contoured, and dose was calculated including mean, max, and max 10 cc dose. Clinical variables including stage, histology, age, gender, Charlson comorbidity index (CCI), preexisting cardiac disease, pulmonary function (forced expiratory volume in 1 second, diffusion capacity), and smoking status were explored for association with non-cancer-related deaths in univariable (UVA) and multivariable (MVA) analyses. Heart dosimetric parameters were correlated with the risk of radiation pneumonitis (RP) using UVA and MVA. RESULTS: A total of 189 patients were included with median age of 76 years (range, 48-93 years). Of these patients, 45.5% were female, 27.5% were T2, 16.9% were current smokers, 64% had preexisting cardiac risk factors, and 34.5% had CCI score of ≥ 3. Mean lung dose ± SD was 456 ± 231 cGy. Heart max, mean, and 10 cc doses were 1867 ± 1712 cGy, 265 ± 269 cGy, and 1150 ± 1075 cGy, respectively. There were 14 (7.4%) ≥ Grade 2 RP and 3 (1.6%) were ≥ Grade 3. The median overall survival was 37.3 months (95% confidence interval, 29.8-45.3 months). On UVA, female gender (P < .01), higher Eastern Cooperative Oncology Group (P = .01), cardiac risk (P < .01), CCI (P < .01), and bilateral ventricles max dose (P = .02) were associated with non-cancer-related deaths; on MVA, bilateral ventricles max dose was significant (P = .05). No heart parameters were associated with RP. CONCLUSIONS: Higher bilateral ventricles max dose is associated with poorer survival. Heart dose parameters should be considered when planning patients for SBRT.

Low Incidence of Esophageal Toxicity After Lung Stereotactic Body Radiation Therapy: Are Current Esophageal Dose Constraints Too Conservative?

PURPOSE: To explore and quantify the relationship between esophageal dose and toxicity in the setting of lung stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: This analysis was conducted on the basis of a prospective study of patients treated with SBRT at our institution from October 2004 to December 2015. Most patients were treated with 54 Gy/3 fractions, 48 Gy/4 fractions alternate days, or 60 Gy/8 fractions daily. Toxicity was prospectively graded using Common Terminology Criteria for Adverse Events version 3.0. Logistic regression was used to estimate the risk of esophageal toxicity as a function of radiation therapy dose, in 2-Gy-equivalent dose, using an α/ß ratio of 3 Gy in the linear-quadratic model. RESULTS: A total of 632 patients were analyzed. The median follow-up was 20.8 months. Median overall survival was 35.3 months. The rate of late or acute grade ≥1 esophageal toxicity, including dysphagia, odynophagia, and esophagitis, was 3.3% (n = 21). The median (range) esophageal doses were 11.8 Gy (0.2-48.2 Gy), 10.34 Gy (0.17-44.5 Gy), and 9.63 Gy (0.08-43 Gy) for Dmax, D1cc, and D2cc, respectively. A 15% risk of esophageal toxicity was associated with a 2-Gy-equivalent dose of Dmax 141.6 Gy, D1cc 123.61 Gy, and D2cc 117.6 Gy. Of the 21 patients who experienced esophageal toxicity, only 1 patient had grade 3 toxicity, and the remainder had grade 2 or lower toxicity. CONCLUSIONS: The observed rate of toxicity was low, despite some patients receiving relatively high doses to the esophagus. A prospective study in a targeted population, for example patients with ultracentral tumors, may provide more accurate dose-toxicity parameters.

Evaluating the Effectiveness of an Electronic Learning Tool for Volumetric Imaging Training-Perceptions of Radiation Therapy Professionals.

PURPOSE: Daily volumetric imaging through cone-beam computed tomography (CBCT) has greatly impacted the roles and responsibilities of radiation therapists (RTTs). A CBCT eLearning module was developed at our cancer centre to equip RTTs with critical thinking skills and clinical judgement required in a CBCT guidance environment. This study aims to evaluate the effectiveness of the electronic module and its impact on the learner's outcome from the perspectives of various radiation therapy professions and to assess the applicability of the eLearning module to RTTs, oncologists, and physicists. METHODS AND MATERIALS: The module "Myths in Cone-Beam Computed Tomography Practice" was evaluated by participants from our in-house accelerated education program. A 21-item questionnaire was developed to assess the module effectiveness. Two cohorts of attendees from the in-house accelerated education program (19 oncologists, 14 physicists, 14 therapists) were asked to voluntarily complete the survey following review of the module. Data analyses were performed between groups to determine differences in their perceptions. RESULTS: Twenty-one participants (5 oncologists, 3 physicists, 13 therapists) responded to the survey yielding a response rate of 44.68%. Survey responses indicate learners found the format user friendly, clear, and easy to navigate. All participants agreed that the electronic format of this module is conducive to learning with 60% agreement that this module is more useful than live sessions; 94.74% agreed that the module increases confidence in practicing image-guided radiation therapy. CONCLUSIONS: This module is a useful resource for all disciplines of radiation medicine. While the electronic format of this module may be useful worldwide in centres requiring training of their employees in volumetric image-guided radiation therapy, live interactive sessions should supplement this training.

Evaluation of high-fidelity simulation training in radiation oncology using an outcomes logic model.

PURPOSE: To evaluate the feasibility and educational value of high-fidelity, interprofessional team-based simulation in radiation oncology. METHODS: The simulation event was conducted in a radiation oncology department during a non-clinical day. It involved 5 simulation scenarios that were run over three 105 minute timeslots in a single day. High-acuity, low-frequency clinical situations were selected and included HDR brachytherapy emergency, 4D CT artifact management, pediatric emergency clinical mark-up, electron scalp trial set-up and a cone beam CT misregistration incident. A purposive sample of a minimum of 20 trainees was required to assess recruitment feasibility. A faculty radiation oncologist (RO), medical physicist (MP) or radiation therapist (RTT), facilitated each case. Participants completed a pre event survey of demographic data and motivation for participation. A post event survey collected perceptions of familiarity with the clinical content, comfort with interprofessional practice, and event satisfaction, scored on a 1-10 scale in terms of clinical knowledge, clinical decision making, clinical skills, exposure to other trainees and interprofessional communication. Means and standard deviations were calculated. RESULTS: Twenty-one trainees participated including 6 ROs (29%), 6 MPs (29%), and 9 RTTs (43%). All 12 cases (100%) were completed within the allocated 105 minutes. Nine faculty facilitators, (3MP, 2 RO, 4 RTTs) were required for 405 minutes each. Additional costs associated with this event were 154 hours to build the high fidelity scenarios, 2 standardized patients (SPs) for a total of 15.5 hours, and consumables.The mean (±SD) educational value score reported by participants with respect to clinical knowledge was 8.9 (1.1), clinical decision making 8.9 (1.3), clinical skills 8.9 (1.1), exposure to other trainees 9.1 (2.3) and interprofessional communication 9.1 (1.0). Fifteen (71%) participants reported the cases were of an appropriate complexity. The importance of further simulation events was rated highly at 9.1/10. CONCLUSIONS: High-fidelity simulation training is feasible and effective in a radiation oncology context. However, such educational activities require significant resources, including personnel and equipment.

ω-3 fatty acids suppress inflammatory cytokine production by macrophages and hepatocytes.

OBJECTIVE: Long-term total parenteral nutrition (TPN) in children is often complicated by parental nutrition-associated liver disease and may even lead to liver failure. Recently, the addition of ω-3 fatty acids to TPN has been shown to reduce the risk of parental nutrition-associated liver disease. The purpose of this study was to explore the anti-inflammatory effects of ω-3 fatty acids (eicosapentaenoic acid [EPA]) to demonstrate the protection of the liver against hepatic steatosis and damage. MATERIALS AND METHODS: Lipopolysaccharide (LPS) and prostaglandin E(2) (PGE(2)) were used to stimulate human macrophages and hepatocytes (THLE-3) to induce in vitro inflammatory condition. The cells were then incubated with either ω-3 (EPA) or ω-6 (arachidonic acid) fatty acids. Supernatants were collected at different time points for the measurement of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10) using enzyme-linked immunosorbent assay. Furthermore, pretreated macrophages by LPS stimulation and after incubation with EPA were added to prestimulated hepatocytes for the subsequent measurement of cytokine response. RESULTS: Eicosapentaenoic acid effectively reduced LPS-induced or PGE(2)-induced TNF-α and IL-6 expression, and increased IL-10 expression significantly when compared with arachidonic acid. Furthermore, supernatant collected after co-culturing EPA with macrophages also suppressed the levels of TNF-α and IL-6 in hepatocytes. This would suggest that EPA not only had an anti-inflammatory effect on macrophages and hepatocytes directly, it could indirectly reduce hepatocyte inflammation through activated macrophages. CONCLUSIONS: The addition of ω-3 fatty acids in TPN suppresses the inflammatory response via direct and indirect routes. The findings may help explain the clinical benefits of EPA in pediatric patients receiving long-term TPN.