Adjunctive Screening Research Articles

Salivary metabolites to detect patients with cancer: a systematic review.

Novel adjunctive screening aids are needed to reduce the morbidity and mortality related to cancer, and every effort should be made for early diagnosis. This systematic review aimed to evaluate salivary metabolites and their diagnostic value in patients with cancer.The systematic review was performed in two phases and included studies that focused on the diagnostic value of salivary metabolites in humans with solid malignant neoplasms. Five electronic databases were searched, and the risk of bias in individual studies was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Of the 1151 studies retrieved, 25 were included; 13 studies used targeted and 12 untargeted metabolomics approaches. Most studies included patients with breast and oral cancer. Except for one, all studies had case-control designs, and none fulfilled all quality assessments. Overall, 140 salivary metabolites were described. The most frequently reported metabolites were alanine, valine, and leucine. Among the 11 studies that reported diagnostic test accuracy (DTA) values, proline, threonine, and histidine in combination and monoacylglycerol alone demonstrated the highest DTA for breast cancer. Combined choline, betaine, pipecolinic acid, and L-carnitine showed better discriminatory performance for early oral cancer.This systematic review highlights the current evidence on salivary metabolites that may be used as a future strategy to diagnose cancer. Further studies including larger sample sizes with confirmation of the results by untargeted analysis are warranted.

Preferences and Attitudes Regarding Adjunct Breast Cancer Screening Among Patients with Dense Breasts.

New breast screening modalities are being investigated to address the need for more sensitive breast cancer screening in women with dense breasts. We investigated the preferences and attitudes of these patients regarding adjunct screening modalities to help evaluate the acceptability of these exams. In this institutional review board-approved prospective study, patients with dense breasts on their prior mammogram were invited to complete a survey. Patients were asked to estimate their personal breast cancer risk compared with peers, indicate their level of concern related to screening callbacks, radiation exposure, and intravenous (IV) contrast allergies, and identify which factors might deter them from getting adjunct screening exams. Five hundred eight patients with dense breasts presenting for screening mammography completed surveys. While most patients (304/508, 59.9%) felt it was likely or very likely that cancer could be missed on their mammogram, only 8.9% (45/508) had undergone adjunct screening exams in the past 3 years. The most commonly cited deterrents to adjunct screening were cost (340/508, 66.9%), pain (173/508, 34.1%), and concern that adjunct screening could lead to additional procedures (158/508, 31.1%). When asked to select among three hypothetical breast cancer screening modalities, patients strongly preferred the more sensitive examination, even if this involved greater cost (162/508, 31.9%) or IV-contrast administration (315/508, 62.0%). Our data suggest that patients with dense breasts prefer adjunct screening exams that are both sensitive and inexpensive, although an increase in sensitivity could outweigh additional cost or even IV-line placement.

Abstract OT3-03-01: Diagnostic value of Three-dimensional UltRasound in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result: The TURB0 study

Abstract Background: Three-dimensional automated whole-breast ultrasound (3D ABUS) is an emerging imaging technique that enables the standardized acquisition of volumetric images of the whole breast. Although more data become available on the added value of 3D ABUS both in the screening and diagnostic setting, to date this technique is not widely used in the Netherlands. In the Netherlands, women between the ages of 50 and 75 years are invited for breast cancer screening every two years using full-field digital mammography. Approximately 2.4% of screening participants is recalled and referred to a hospital for diagnostic work-up of inconclusive (BI-RADS 0) or suspicious findings (BI-RADS 4/5). While over half of recalls from screening results from a BI-RADS 0 screening mammography, only 11% of these women has breast cancer. However, invasive diagnostic procedures are performed in every one in five women with a false-positive BI-RADS 0 recall. False-positive screening mammography results cause anxiety in the patient, especially when a biopsy is necessary. Furthermore, the diagnostic work-up after referral is costly and exerts pressure on health care facilities. 3D ABUS may be of added diagnostic value in women recalled from screening with a BI-RADS 0 mammography result. 3D ABUS may potentially lower the number of benign biopsies in the diagnostic setting and, in a future perspective, decrease the false-positive recall rate when used as an adjunct screening tool in women with a BI-RADS 0 screening mammography result. Therefore, we aim to investigate the diagnostic accuracy and added value of 3D ABUS in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result. Trial design: Observational multicenter prospective cohort study. The study was approved by the Medical Research Ethical Committee of the University Medical Center Utrecht. Written informed consent is obtained from all participants. In addition to screening mammography, tomosynthesis and hand-held ultrasound, bilateral, supine 3D ABUS imaging is obtained. Different imaging strategies are compared to determine the optimal combination of imaging modalities and the added value of 3D ABUS. Eligibility criteria: Women recalled from Dutch breast cancer screening with a BI-RADS 0 screening mammography result and able to give informed consent are considered eligible. Aim: To investigate the diagnostic accuracy and added value of 3D ABUS in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result. Statistical methods: Sensitivity, specificity, negative predictive value and positive predictive value of 3D ABUS will be calculated with 95% confidence intervals, using histopathology (if available) or follow up to the next screening round approximately two years later as the reference standard. The diagnostic accuracy of different imaging strategies in the diagnostic work-up will be compared with pairwise McNemar tests and area under the receiver operating characteristic curve analyses. A p-value <0.05 will be considered statistically significant. Screening mammography will be assessed in combination with 3D ABUS imaging to calculate the number of false-positive BI-RADS 0 recalls that 3D ABUS may prevent. Subgroup analysis will be performed based on four breast density categories, measured with automated breast density software, to evaluate the added value of 3D ABUS specifically in women with dense breasts. Present accrual: 360 (April 2018 - June 2019). Target accrual: 600 (expected in April 2020) Acknowledgements: The TURB0 study is funded by General Electric. Hologic provided the breast density assessment software for the purpose of this study. Contact information: B.M.denDekker-3@umcutrecht.nl Citation Format: Bianca M den Dekker, Mireille JM Broeders, Helena M Verkooijen, Alexander Venmans, Carla Meeuwis, Wikke Setz-Pels, Ruud M Pijnappel. Diagnostic value of Three-dimensional UltRasound in women recalled from Dutch breast cancer screening with a BI-RADS 0 mammography result: The TURB0 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-03-01.

Noninvasive assessment of oral lesions using elastic light single-scattering spectroscopy: a pilot study.

In the present study, we investigated the potential application of elastic light single-scattering spectroscopy (ELSSS) as a noninvasive, adjunctive tool to differentiate between malignant and benign oral lesions in vivo. ELSSS spectra were acquired from 52 oral lesions of 47 patients prior to surgical biopsy using a single optical fiber probe. The sign of the spectral slope was used as a diagnostic parameter and was compared to the histopathology findings to obtain sensitivity and specificity of the ELSSS system in differentiating between benign and malignant tissues. The sign of the spectral slope was positive for the benign tissues and negative for the malignant tissues. Nine malignant lesions and one high-grade dysplasia were correctly classified as cancerous. Six out of the ten low-grade dysplasia were correctly classified as cancerous, and four of them were misclassified as benign. Thirty benign lesions were correctly classified as benign, and two were misclassified as malignant. Our results indicate that the sign of the spectral slope enables the differentiation between malignant and benign oral lesions with a sensitivity of 80% and specificity of 94%. ELSSS has the potential to be developed as an adjunctive screening tool in the noninvasive evaluation of oral lesions in vivo. This new diagnostic system may reduce the number of unnecessary biopsies.

Cost-Effectiveness of Preoperative OCT in Cataract Evaluation for Multifocal Intraocular Lens

To determine the cost effectiveness of an adjunctive screening OCT during the preoperative evaluation of a patient considering cataract surgery with a multifocal intraocular lens (IOL) implantation. Cost-effectiveness analysis. A 67-year-old man with 20/60 vision undergoing evaluation for first-eye cataract surgery. The cost-effectiveness analysis of the reference patient undergoing a preoperative cataract examination with and without a screening OCT was performed, evaluating for vitreoretinal diseases including an epiretinal membrane, age-related macular degeneration, vitreomacular traction, and cystoid macular edema. It was assumed that patients with macular pathologies detected before surgery would receive a monofocal IOL and be referred to a retina specialist for evaluation and management. The Medicare reimbursable cost of an OCT was $41.81. All costs and benefits were adjusted for inflation to 2019 United States dollars and discounted 3% per annum over a 16-year time horizon. Probability sensitivity analyses and 1-way deterministic sensitivity analyses were performed to assess for uncertainty. Incremental cost-effectiveness ratio and incremental cost-utility ratio (ICUR) measured in quality-adjusted life years (QALYs). Approximately 20.5% of patients undergoing cataract surgery may have macular pathologies, of which 11% may not be detected on the initial clinical examination. In the base case, an adjunctive preoperative OCT was cost effective from a third-party payer and societal perspective in the United States. In the probability sensitivity analyses, the ICURs were within the societal willingness-to-pay threshold of $50 000/QALY in approximately 64.4% of the clinical scenarios. A preoperative screening OCT during the evaluation of a patient considering a multifocal IOL added to the costs of the cataract surgery, but the OCT increased the detection of macular pathologies and improved the QALYs over time. An adjunctive screening OCT can be cost effective from a third-party payer and societal perspective.

Influence of Breast Density on Patient's Compliance during Ultrasound Examination: Conventional Handheld Breast Ultrasound Compared to Automated Breast Ultrasound.

Background:Our aim was to study the influence of breast density on patient's compliance during conventional handheld breast ultrasound (US) or automated breast US (ABUS), which could be used as adjunct screening modalities.Methods:Between January 2019 and June 2019, 221 patients (mean age: 53; age range: 24–89 years) underwent both US and ABUS. All participants had independently interpreted US and ABUS regarding patient compliance. The diagnostic experience with US or ABUS was described with a modified testing morbidity index (TMI). The scale ranged from 0 (worst possible experience) to 5 (acceptable experience). Standard statistics was used to compare the data of US and data of ABUS. Breast density was recorded with the Breast Imaging Reporting and Data System (BI-RADS) score.Results:The mean TMI score was 4.6 ± 0.5 for US and 4.3 ± 0.8 for ABUS. The overall difference between patients' experience on US and ABUS was statistically significant with P < 0.0001. The difference between patients' experience on US and ABUS in women with BI-RADS C and D for breast density was statistically significant with P < 0.02 in favor of US (4.7 ± 0.4) versus 4.5 ± 0.6 for ABUS. Patients' experience with breast density B was better for US (4.7 ± 0.4) versus 4.3 ± 0.6 for ABUS with P < 0.01. Pain or discomfort occurred during testing, especially in patients >40 years.Conclusion:Patient age (>40 years) is a significant predictor of decreased compliance to ABUS. Compliance of ABUS resulted lower that of US independently for breast density.

Testing NTRK testing: Wet-lab and in silico comparison of RNA-based targeted sequencing assays.

NTRK fusions involving three neurotrophic tyrosine receptor kinase genes NTRK1, NTRK2, and NTRK3 and a variety of fusion partners were identified as oncogenic drivers across many cancer types. Drugs that target the chimeric protein product require the identification of the underlying gene fusion. This advocates the diagnostic use of molecular assays ranging from fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR)/Sanger approaches to targeted next-generation sequencing (NGS). Immunohistochemistry may be used as a screening tool and adjunct diagnostic assay in this context. Although FISH and RT-PCR/Sanger approaches are widely adopted in routine diagnostics, current experience with targeted RNA-based NGS is limited. Here, we report on the analysis of major assays (TruSight TST170 and TruSight RNA Fusion [Illumina]; Archer FusionPlex Solid Tumor, Archer FusionPlex Lung, and Archer FusionPlex Oncology [Archer]; Oncomine Comprehensive Assay v3 RNA and Oncomine Focus RNA [Thermo Fisher Scientific]) that are commercially available. The data set includes performance results of a multicentric comparative wet-lab study as well as an in silico analysis on the ability to detect the broad range of NTRK fusions reported until now. A test algorithm that reflects assay methodology is provided. This data will support implementation of targeted RNA sequencing in routine diagnostics and inform screening and testing strategies that have been brought forward.

Clinical Infrared Imaging in the Prone Position for Breast Cancer Screening—Initial Screening and Digital Model Validation

AbstractBreast cancer is the most prevalent form of cancer in women with over 266,000 new cases diagnosed every year in the United States. The various methods used for breast cancer screening range in accuracy and cost; however, there is no easily reproducible, reliable, low-cost, nonradiative screening modality currently available, especially for dense breast tissue. Steady-state infrared imaging (IRI) is promising in this area as it is unaffected by tissue density and has the potential to detect tumors by measuring and capturing the thermal profile on the breast surface induced by increased blood perfusion and metabolic activity associated with the tumor. In our proposed clinical IRI and simulation approach (CIRIS™), women with biopsy-proven breast cancer are imaged with IRI in the prone position. The prone position is able to provide a thermal profile of the entire breast without any gravitational deformation or thermal abnormalities in the inframammary fold. A digital model, created using clinical images, is thermally simulated through a commercially available software using known tumor characteristics obtained from the available magnetic resonance imaging (MRI) data. The resulting surface thermal profile is compared with the IRI images. In the three cases discussed here, the digital model was able to accurately predict the breast surface temperature distribution, showing the promise of this approach in breast cancer screening. This preliminary work is expected to lead the way for a larger clinical study in the future to establish IRI as an adjunctive screening technique.

P3436T-wave inversion in middle age is associated with higher mortality risk compared to occurrence of a new T-wave inversion later in life

Abstract Background Minor ECG abnormalities, such as T-wave inversions, are frequently seen in clinical practice in asymptomatic patients. Its prognostic role is incompletely studied. We have previously reported an association between T-wave inversion, and all-cause mortality during lifetime. Purpose To study the prognostic prediction of new-onset of T-wave inversion in ECG recorded at various ages, in a male random population-based cohort in lifetime follow up. Methods Subjects from a random longitudinal, prospective, population-based study: “The study of men born in 1913” (n=854) were examined at 50-years of age and re-examined at 60, 67, 75 and 80 years, including a 12-lead ECG recording, classified according to the Minnesota code. Participants were followed until death or year 2015 (48 years follow-up), and data were obtained through the Cause of Death Register. Unadjusted and adjusted Cox proportional hazards models, producing an overall hazard ratio (HR), and flexible parametric models for survival data by Royston and Parmar, producing continuous HR over studied time, were applied for prediction of time to all-cause death and cardiovascular disease (CVD) death by the incident negative T-wave. Results An increased risk of all-cause and CVD death associated with negative T-waves was evident at the majority of observational ages in unadjusted analyses. After adjustment for other conditions (smoking, physical activity level, BMI, systolic blood pressure (BP), hypertension, BP medication, s-cholesterol, hematocrit, Q/QS patterns, and ST-junction/segment depression), a negative T-wave at 50 years of age was significantly associated with all-cause and CVD death, [HR 1.46 (95% CI 1.06–2.01), p=0.021, and HR 1.58 (95% CI 1.06–2.36), p=0.025], respectively. However, the HR of 1.58 for CVD death interacted significantly with time (p=0.034), with greater risk in the years adjacent to observation than for later follow-up (Figure, right panel). The corresponding adjusted analyses of a newly diagnosed negative T-wave appearing at 60, 67 and 75 years were not statistically significant for either of the two outcomes. However, an incident negative T-wave at 80 years of age was shown to have numerically higher overall impact, but not statistically significant for all-cause death [HR 1.52 (95% CI 0.80–2.86), p=0.20], but for CVD death [HR 2.41 (95% CI 1.03–5.66), p=0.043], with no significant interaction with time. Conclusion In this population cohort, a first time registered negative T-wave at 50 years carried a considerably increased risk of mortality, specifically CVD mortality, which cannot be explained by other cardiovascular risk factors. The risk was greatest in middle age, and weakened with increasing age. Our findings warrant verification in other cohorts. If an independent risk indication of negative T-wave at middle age is confirmed it could be a valuable adjunct in screening and cardiovascular risk assessment. Acknowledgement/Funding Sweden Heart-Lung Foundation, ALF Västra Götalandsregionen-Göteborgs Universitet

A Prospective Study of Methylmercury Exposure and Prepulse Inhibition Deficits in Children and Adolescents

OPS 38: Effects of metals on child health, Room 114, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background: Methylmercury (MeHg) exposure has been associated with severe and subtle neurodevelopmental deficits, especially in children. Pre-Pulse Inhibition (PPI), an indicator of adequate sensorimotor gating processing is a neurological biomarker that may be useful for identifying neurodevelopmental deficits earlier and more objectively than behavioral ratings. Furthermore, PPI may be more cost-effective than current brain imaging techniques for assessing the effects of neurotoxicants such as MeHg. Objective: This study examined the association between MeHg exposure and PPI deficits in a prospective cohort of children and adolescents from Mexico City. Methods: We obtained venous whole blood samples and scalp hair samples at two time points from 176 offspring from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohort; the PPI evaluation was completed at the second time point, approximately 18 months after the first time point. PPI recording and analysis occurred in an isolated clinical setting and eye blink responses were assessed using electromyography. We used ordinary least squares regression models adjusted for maternal education, maternal IQ, birthweight, child’s sex, and child’s age (predictors of PPI and MeHg) to assess the relationship between earlier and concurrent MeHg concentrations on PPI deficits. Results: The spearman correlation coefficient for blood- and hair-MeHg levels was 0.68 (p < .0001) and 0.73 (p < .0001) at the two visits, respectively. In adjusted models, one µg/L increase in earlier blood-MeHg concentrations was significantly associated with a 0.22 point decrease in PPI (95% CI: 0.07, 0.37). We observed no associations between concurrent blood-MeHg, hair-MeHg concentrations and PPI deficits. Conclusions: In our study population, blood-MeHg concentrations were associated with PPI deficits, which is consistent with MeHg’s known neurotoxicity. Our results underscore the potential utility of PPI as an objective and cost-effective adjunct screening tool for assessing neurotoxicant effects on the brain.

Abstract 4223: Conducting community oral cancer screening among South Asians in British Columbia

Abstract Introduction: Globally, more than 300,000 cases of oral cancer are diagnosed annually. South Asian countries, such as India, bear the brunt of this disease due to rampant use of chewing tobacco, betel quid and areca nut. BC has a high proportion of South Asian immigrants. Oral cancer has a high mortality rate (~50% 5-year survival) due to the advanced stage at which it is often diagnosed. It is purported that the majority of oral cancers develop from oral potentially malignant lesions (OPML). While lesions can be easily detected by oral health care providers, it can be challenging to differentiate benign lesions from OPML. DNA aneuploidy has been shown to be an effective marker to predict malignant transformation in OPML. Quantitative cytology (QC) studies DNA content (ploidy) and nuclear morphometric changes within the cell. The aim of this project is to assess the need for oral cancer screening in South Asians in BC and to validate QC as an adjunct screening device in a predominantly South Asian community screening setting to assess its effectiveness in identifying high-risk lesions among visually suspicious lesions. Methods: Demographic information (gender, age, country of birth, ethnicity, risk habit information and dental usage) were collected at the time of screening. Extraoral, intraoral and fluorescence visualization (FV) examinations were conducted. Buccal mucosal brushings were collected from each participant. Brushings were also collected from lesions or areas that had a loss of fluorescence. Thin-layer cytology slides were prepared and stained using Feulgen Eosin. Slides were scanned using the Cancer Imaging Scanner at BC Cancer using machine learning classification algorithms to identify single, in-focus epithelial nucleus. Cells are classified based on DNA ploidy and malignant associated changes. Results: 307 participants were screened of which 303 were eligible. More than 99% of the participants were South Asian or Asian. 104 (34%) lesions were documented: 45 (15%) were high risk (white or red lesions, lichen planus (LP)) and 59 (19%) were low risk (trauma, candidiasis, aphthous ulcers). Twenty participants (7%) were suspected to have high-risk OPMLs (not LP): 12 were referred directly to our Next Gen Oral Dysplasia clinic for biopsy, while 8 were reassessed at 3 weeks. Chewing tobacco was found to be strongly associated with lesion presence (p&amp;lt;0.01). QC analysis is ongoing for 320 samples. To date, 5 biopsies have been performed resulting in 1 mild dysplasia, 1 severe dysplasia and 3 hyperplasia. Conclusion: South Asians in BC were found to be at high risk for OPMLs. QC may help to improve the sensitivity and specificity of oral cancer screening by distinguishing false FV positive inflammatory lesions from high-risk lesions. Citation Format: Leigha D. Rock, Madhurima Datta, Denise M. Laronde, Anita Carraro, Jagoda Korbelik, Alan Harrison, Martial Guillaud. Conducting community oral cancer screening among South Asians in British Columbia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4223.

Socio-demographic predictors of prepulse inhibition: A prospective study in children and adolescents from Mexico City

Prepulse inhibition (PPI) is a sensorimotor gating mechanism that reduces interfering influences to the neural processing of incoming stimuli, and is associated with several neurodevelopmental disorders. To date, research on PPI and neurodevelopmental disorders has primarily been in cross-sectional, clinical settings. In this prospective, epidemiologic study, we used a data-driven prediction model to identify socio-demographic predictors of PPI in children and adolescents from Mexico City to inform future etiologic studies evaluating PPI. We conducted variable selection and validation using a modified version of the multiple imputation random lasso (MIRL) variable selection algorithm. MIRL identified six predictors of PPI at a stimulus onset asynchrony of 120 ms or 240 ms. Of those six predictors, maternal education, birthweight, and total breastfeeding months were highlighted as previously unstudied variables associated with enhanced PPI. Our findings highlight the potential value of PPI as an adjunct screening tool for identifying children at risk for neurodevelopmental disorders and underscore the relevance for validation research on this topic.

Evaluation of a Lectin-Based Imaging System for the Chairside Detection of Oral Dysplasia and Malignancy

Currently available oral cancer screening adjuncts have not enhanced clinical screening methods because of high false positives and negatives, highlighting the need for a molecularly specific technique for accurate screening of suspicious oral lesions. The purpose of this study was to evaluate the invivo screening accuracy of an oral lesion identification system that evaluates aberrant glycosylation patterns using a fluorescently labeled lectin (wheat germ agglutinin and fluorescein isothiocyanate [WGA-FITC]). The authors designed and implemented a prospective cohort study at 3 institutions composed of patients with and without suspicious oral lesions. Oral cavities were screened by clinical examination and with the oral lesion identification system according to a stepwise procedure that included the topical application and fluorescence visualization of a fluorescent nuclear stain and WGA-FITC. Tissue samples were obtained from all enrolled patients for histopathological diagnosis and were used to calculate sensitivity and specificity metrics (primary outcome variable) irrespective of the oral lesion identification system result. The sample was composed of 97 patients; 86 had 100 clinically suspicious lesions and 11 without such lesions were included as a control group. Use of the oral lesion identification system resulted in 100, 100, and 74% sensitivity for cancer, high-grade dysplasia, and low-grade dysplasia, respectively, and a specificity of 80%. Clinical diagnosis yielded similar sensitivity values of 84, 100, and 88% for cancer, high-grade dysplasia, and low-grade dysplasia, respectively, and a specificity of 76%. Use of the oral lesion identification system enhanced the visualization of lesion dimensionality and borders. The results of this study suggest the oral lesion identification system was a beneficial adjunct to standard clinical examination, because the system provided sensitivity and specificity values similar to or greater than clinical diagnosis.

Optical Coherence Tomography as an Oral Cancer Screening Adjunct in a Low Resource Settings

Oral cancer is the sixth most common cancer worldwide, predominantly seen in low and middle-income countries (LMIC). Two thirds of all cases are detected at a late stage when prognosis and treatment outcomes are poor. Oral lesions are commonly detected by visual inspection, followed by invasive surgical biopsy and time-consuming histopathological analysis. Optical coherence tomography (OCT), a minimally invasive tomographic imaging technology, can be used to non-invasively identify premalignant or malignant change in the oral mucosa. In this study, a mobile OCT imaging system was designed, constructed, and tested for its performance as a point-of-care oral diagnostic device in an LMIC. 20 patients with suspicious oral lesions and 10 healthy subjects were enrolled in this pilot study. Two-dimensional (2-D) OCT images as well as clinical examination data, risk habit history, and histopathology were collected. OCT images for healthy oral mucosa, dysplasia, and malignancy were evaluated in a blinded fashion by visual scoring and computed image processing techniques. It was found that the OCT image processing algorithm performed at or exceeded the performance of visual observer scoring of OCT images.

Comparison of Aberrant Behavior Checklist profiles across Prader-Willi syndrome, Down syndrome, and autism spectrum disorder.

Prader-Willi syndrome (PWS, OMIM # 176270) and Down syndrome (DS, OMIM #190685) are neurodevelopmental genetic disorders with higher rates of autism spectrum disorder (ASD). The Aberrant Behavior Checklist (ABC) is a caregiver rating scale that assesses maladaptive behaviors. Overlapping symptoms exist between PWS, DS, and ASD, including maladaptive behaviors. We aimed to evaluate ABC profiles between PWS, DS, and ASD alone (without known genetic syndrome). In addition, we hypothesized PWS and DS with a comorbid ASD positive screen or diagnosis would have similar ABC profiles to ASD alone. ABC data from the following cohorts were analyzed: PWS (Seattle Children's Hospital, n = 28, mean age = 12.8 ± 4.9 years; University of Florida, n = 35, mean age = 9.3 ± 7.1 years), DS (Johns Hopkins, n = 406, mean age = 8.1 ± 2.4 years), and ASD (University of Florida, n = 102, mean age = 10.8 ± 3.5 years). ASD alone had significantly higher ABC scores. Subgroups of PWS and DS with a comorbid ASD positive screen or diagnosis had similarities in scores with the ASD only group, with subscale patterns unique to each syndrome. The ABC indicated worse maladaptive behaviors in children with ASD, including those with genetic syndromes. Although more studies are needed to evaluate the utility and the accuracy of the ABC as a tool to screen for ASD in special populations, it may be a useful adjunct in screening those children with PWS or DS who need more in depth ASD evaluation.

En Face Optical Coherence Tomography Imaging of the Photoreceptor Layers in Hydroxychloroquine Retinopathy

To investigate the application of en face optical coherence tomography (OCT) imaging in eyes with hydroxychloroquine (HCQ) retinopathy. Retrospective case series. Setting: Institutional. Sixty-two eyes of 31 Asian patients with HCQ retinopathy. Macular volume scanning using swept-source OCT was performed in 6× 6-mm and 9× 9-mm areas centered on the fovea. Segmentation of the photoreceptor layers was automatically performed between the inner border of the ellipsoid zone and that of the retinal pigment epithelium-Bruch membrane complex to obtain en face OCT images. Findings from the en face images were qualitatively and quantitatively evaluated; they were analyzed and correlated with the fundus autofluorescence and visual field findings. En face OCT findings. All eyes with HCQ retinopathy had a beaten-bronze appearance in the areas with photoreceptor defects, whereas those with intact photoreceptors had areas with smooth surfaces, which were occasionally demarcated by hyporeflective margins, on the en face OCT images. The presence and extent of the retinopathy could be quickly determined using the images. They also provided quantitative information on the progression based on the areas of intact photoreceptors compared over several visits. Furthermore, the area of central intact photoreceptors significantly correlated with the mean deviation, pattern standard deviation, and visual field index of 30-2 visual field examinations (all P < .001). En face OCT may be useful for visualizing the presence and extent of HCQ retinopathy and its progression. The area of central intact photoreceptors measured on en face OCT images showed a significant association with functional visual field defects. This imaging may be a helpful adjunct for screening and follow-up examinations of HCQ retinopathy.

A prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2)

BackgroundIncreased risk of breast cancer (BC) and increased risk of an interval BC at mammography screening are associated with high mammographic density. Adjunct imaging detects additional BCs not detected at mammography screening in women with dense breasts. AimThe aim is to estimate the incremental cancer detection rate (CDR) and false-positive recall for each of tomosynthesis and ultrasound, as adjunct screening modalities in women with mammography-negative dense breasts. MethodsA multicentre prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2) recruited asymptomatic women attending Italian breast screening services. All participants had independently interpreted tomosynthesis and ultrasound. Outcomes were ascertained from excision histopathology or completed assessment. Paired binary data were compared using McNemar's test. ResultsWe recruited 5300 screening participants with median age of 50 (interquartile range 43–79) years who had negative mammography and dense breasts (April 2015–September 2017). Adjunct screening detected 29 additional BCs (27 invasive, 2 in situ): 12 detected on both tomosynthesis and ultrasound, 3 detected only on tomosynthesis, 14 detected only on ultrasound. Incremental CDR for tomosynthesis (+15 cancers) was 2.83/1000 screens (95% confidence interval [CI]: 1.58–4.67) versus ultrasound (+26 cancers) with an incremental CDR of 4.90/1000 screens (95% CI: 3.21–7.19), P = 0.015. Mean size of these cancers was 14.2 mm (standard deviation: 7.8 mm), and six had nodal metastases. Incremental false-positive recall was 1.22% (95% CI: 0.91%–1.49%) and differed significantly between tomosynthesis (0.30%) and ultrasound (1.0%), P < 0.001. ConclusionsUltrasound detected more BCs but caused more false positives than tomosynthesis, underscoring trade-offs in screening outcomes when adjunct imaging is used for screening dense breasts.

Salivary Human Epidermal Growth Factor Receptors 2 Levels in Patients With Different Stages of Breast Cancer: A Cross Sectional Study

Background: Breast cancer in women is a major health burden across the globe, which accounts for 12% of all new cancer cases and 25% of all cancers in women. Though studies have demonstrated a significant reduction in mortality and morbidity by periodic screening using mammography, its cost and exposure to radiation are prohibitive factors in subjecting the patients to a repetitive mammogram examination. Hence additional adjunct procedures which can overcome these disadvantages and enhance screening are advocated. Human epidermal growth factor receptor-2 (c-erbB-2) is a biomarker that can be detected in saliva of breast cancer patients. An elevated level of this protein indicates the presence of an aggressive tumor with poor prognosis. Aim: The aim of our study was to determine the levels of salivary c-erbB-2 in patients diagnosed with different stages of breast cancer. Methods: 90 patients, histopathologically diagnosed with breast cancer were divided into three groups based on TNM staging (Stage I, II, and III) with 30 patients in each group. 3 ml of unstimulated saliva was collected from these patients and the protein was estimated using ELISA kit. Appropriate statistical tests were used to analyze the demographic details and mean salivary c-erbB-2 levels. Results: The mean salivary c-erbB-2 levels in groups I, II and III were 9.933(±5.105), 59.633(±17.14) and 146.695(±22.418) picograms/mL respectively. There was a significant increase in the levels of the protein with an increase in the TNM staging in patients with breast cancers. Conclusion: This study results throws light on the potential use of salivary c-erB-2 as an adjunct screening and prognostic tool for breast cancer. However further studies are recommended to assess the utility of this biomarker for the diagnosis and posttreatment monitoring of breast cancer.

Screening Ultrasound for Women with Dense Breasts in the Age of Patient-centered Care

As the field of medicine moves toward practicing patient-centered care, radiologists in breast imaging must continue to look for ways to increase the value of their practice in the eyes of patients. Providing adjunct screening of women with dense breasts provides such an opportunity. The presence of dense breast tissue is not only an independent risk factor for breast cancer but also a risk factor for the delayed diagnosis of breast cancer as dense tissue reduces the efficacy of screening mammograms due to the tissue masking effect. As legislation for notifying women of their breast density becomes commonplace, both women and referring physicians need to understand the risks of dense breast tissue as well as the benefits of additional screening affords. Breast radiologists can become integral to their patients’ care team by offering education to both referring providers and patients on the topic of dense breasts and supplemental screening solutions, such as screening breast ultrasound, which has been shown to have benefit in overcoming mammography’s shortcomings in this demographic of women.

Use of Ultrasound in Male Infertility: Appropriate Selection of Men for Scrotal Ultrasound.

Male factor infertility is a complex and multifaceted problem facing the modern urologist and is identified in 30-40% of infertile couples. This review focuses on the use of ultrasound, as an adjunct screening tool, in the initial evaluation of male infertility. Access to male reproductive urologist for assessment of male infertility is limited and about a quarter of infertile couples do not complete the male component in their infertility assessment. Ultrasound evaluation of the infertile male is low-cost and non-invasive and helps uncover underlying pathologies that may be missed during the initial assessment. The addition of ultrasound allows the physician to accurately assess testicular anatomy and dimensions, as well as vascular environments, which may help guide treatment decisions. Scrotal ultrasound evaluation, in conjunction with a semen analysis and as an adjunct to physical exam, can be offered in the initial assessment of men who present for infertility consultation given its low cost, non-invasive nature, and ability to detect and discriminate between various etiologies of male infertility. Further, when directed by physical exam and semen analysis findings, it provides a valuable tool to select men for referral to a reproductive urologist, especially for infertile couples who are only screened by reproductive endocrinologists and female infertility specialists.