BackgroundTraditionally, chronic wound infection is diagnosed by visual inspection under white light and microbiological sampling, which are subjective and suboptimal, respectively, thereby delaying diagnosis and treatment. To address this, we developed a novel handheld, fluorescence imaging device (PRODIGI) that enables non-contact, real-time, high-resolution visualization and differentiation of key pathogenic bacteria through their endogenous autofluorescence, as well as connective tissues in wounds.Methods and FindingsThis was a two-part Phase I, single center, non-randomized trial of chronic wound patients (male and female, ≥18 years; UHN REB #09-0015-A for part 1; UHN REB #12-5003 for part 2; clinicaltrials.gov Identifier: NCT01378728 for part 1 and NCT01651845 for part 2). Part 1 (28 patients; 54% diabetic foot ulcers, 46% non-diabetic wounds) established the feasibility of autofluorescence imaging to accurately guide wound sampling, validated against blinded, gold standard swab-based microbiology. Part 2 (12 patients; 83.3% diabetic foot ulcers, 16.7% non-diabetic wounds) established the feasibility of autofluorescence imaging to guide wound treatment and quantitatively assess treatment response. We showed that PRODIGI can be used to guide and improve microbiological sampling and debridement of wounds in situ, enabling diagnosis, treatment guidance and response assessment in patients with chronic wounds. PRODIGI is safe, easy to use and integrates into the clinical workflow. Clinically significant bacterial burden can be detected in seconds, quantitatively tracked over days-to-months and their biodistribution mapped within the wound bed, periphery, and other remote areas.ConclusionsPRODIGI represents a technological advancement in wound sampling and treatment guidance for clinical wound care at the point-of-care.Trial RegistrationClinicalTrials.gov NCT01651845; ClinicalTrials.gov NCT01378728

Background The Ontario Breast Screening Program expanded in July 2011 to screen high-risk women age 30–69 years with annual magnetic resonance imaging (MRI) and digital mammography. This study examined the benefits of screening with mammography and MRI by age and risk criteria. Methods This prospective cohort study included 8782 women age 30–69 years referred to the High Risk Ontario Breast Screening Program from July 2011 to June 2015, with final results to December 2016. Cancer detection rates, sensitivity, and specificity of MRI and mammography combined were compared with each modality individually within risk groups stratified by age using generalized estimating equation models. Prognostic features of screen-detected breast cancers were compared by modality using Fisher exact test. All P values are two-sided. Results Among 20 053 screening episodes, there were 280 screen-detected breast cancers (cancer detection rate = 14.0 per 1000, 95% confidence interval [CI] = 12.4 to 15.7). The sensitivity of mammography was statistically significantly lower than that of MRI plus mammography (40.8%, 95% CI = 29.3% to 53.5% vs 96.0%, 95% CI = 92.2% to 98.0%, P < .001). In mutation carriers age 30–39 years, sensitivity of the combination was comparable with MRI alone (100.0% vs 96.8%, 95% CI = 79.2% to 100.0%, P = .99) but with statistically significantly decreased specificity (78.0%, 95% CI = 74.7% to 80.9% vs 86.2%, 95% CI = 83.5% to 88.5%, P < .001). In women age 50–69 years, combining MRI and mammography statistically significantly increased sensitivity compared with MRI alone (96.3%, 95% CI = 90.6% to 98.6% vs 90.9%, 95% CI = 83.6% to 95.1%, P = .02), with a small but statistically significant decrease in specificity (84.2%, 95% CI = 83.1% to 85.2% vs 90.0%, 95% CI = 89.2% to 90.9%, P < .001). Conclusions Screening high risk women age 30–39 years with annual MRI only may be sufficient for cancer detection and should be evaluated further, particularly for mutation carriers. Among women age 50–69 years, detection is most effective when mammography is included with annual MRI.

Risk assessment by parenchymal density pattern, a strong physical indicator of future breast cancer risk, is available with the onset of mammographic screening programmes. However, due to the use of ionizing radiation, mammography is not recommended for use in younger women, thereby rendering risk assessment unattainable at an earlier age. Visible and near infrared light was used on 292 women with radiologically normal mammograms to determine whether transillumination breast spectroscopy (TIBS) can identify women with a high parenchymal density pattern as an intermediate indicator of breast cancer risk. Principal component analysis (PCA) was used to reduce the spectral data and generate density scores for each woman. To assess the accuracy of TIBS, logistic regression was used to calculate crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for each score. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were also calculated for the crude and adjusted logistic models. Optical information relating to tissue chromophores, such as water, lipid and haemoglobin content, was sufficient to identify women with high parenchymal density. The resulting AUC for the final and most parsimonious multivariate logistic model was 0.922 (95% CI 0.878-0.967). TIBS provides information correlating to high parenchymal density and is a promising tool for risk assessment, particularly for younger women.