Technical and clinical considerations of a physical liver phantom for CT radiomics analysis.

OBJECTIVE: This study identifies key characteristics to help build a physical liver computed tomography (CT) phantom for radiomics harmonization; particularly, the higher-order texture metrics. MATERIALS AND METHODS: CT scans of a radiomics phantom comprising of 18 novel 3D printed inserts with varying size, shape, and material combinations were acquired on a 64-slice CT scanner (Brilliance 64, Philips Healthcare). The images were acquired at 120 kV, 250 mAs, CTDIvol of 16.36 mGy, 2 mm slice thickness, and iterative noise-reduction reconstruction (iDose, Philips Healthcare, Andover, MA). Radiomics analysis was performed using the Cancer Imaging Phenomics Toolkit (CaPTk), following automated segmentation of 3D regions of interest (ROI) of the 18 inserts. The findings were compared to three additional ROI obtained of an anthropomorphic liver phantom, a patient liver CT scan, and a water phantom, at comparable imaging settings. Percentage difference in radiomic metrics values between phantom and tissue was used to assess the biological equivalency and <10% was used to claim equivalent. RESULTS: The HU for all 18 ROI from the phantom ranged from -30 to 120 which is within clinically observed HU range of the liver, showing that our phantom material (T3-6B) is representative of biological CT tissue densities (liver) with >50% radiomic features having <10% difference from liver tissue. Based on the assessment of the Neighborhood Gray Tone Difference Matrix (NGTDM) metrics it is evident that the water phantom ROI show extreme values compared to the ROIs from the phantom. This result may further reinforce the difference between a structureless quantity such as water HU values and tissue HU values found in liver. CONCLUSION: The 3-D printed patterns of the constructed radiomics phantom cover a wide span of liver tissue textures seen in CT images. Using our results, texture metrics can be selectively harmonized to establish clinically relevant and reliable radiomics panels.

Evaluation of a Guided Nature and Forest Therapy Walk for Internal Medical Residents - A Brief Report.

Background: Medical residents commonly face compassion fatigue, burnout, anxiety, and depression. Studies of nature-based interventions show improved mental and physical health; few focus on healthcare providers. Objective: To explore potential benefits of forest bathing for medical residents' wellbeing. Methods: Using the Association of Nature and Forest Therapy's framework, we piloted a forest bathing intervention among medical residents with pre/post-participation surveys assessing perceptions of mindfulness and psychological wellbeing. Responses were analyzed using a Fisher's exact test and Student's t-test for independent samples. Results: Fourteen of fifteen participants completed both surveys. We observed significantly improved mindfulness scores and expressions of feeling calm, vital, or creative, as well as a decreased sense of anxiety and depression. Nonsignificant trends towards decreased burnout and irritability were seen. Conclusion: This quality improvement pilot demonstrates trends that forest bathing can improve medical residents' psychological wellbeing and mindfulness. Further exploration of this intervention for healthcare providers is warranted.

Investigating the role of imaging factors in the variability of CT-based texture analysis metrics.

OBJECTIVE: This study assesses the robustness of first-order radiomic texture features namely interquartile range (IQR), coefficient of variation (CV) and standard deviation (SD) derived from computed tomography (CT) images by varying dose, reconstruction algorithms and slice thickness using scans of a uniform water phantom, a commercial anthropomorphic liver phantom, and a human liver in-vivo. MATERIALS AND METHODS: Scans were acquired on a 16 cm detector GE Revolution Apex Edition CT scanner with variations across three different nominal slice thicknesses: 0.625, 1.25, and 2.5 mm, three different dose levels: CTDIvol of 13.86 mGy for the standard dose, 40% reduced dose and 60% reduced dose and two different reconstruction algorithms: a deep learning image reconstruction (DLIR-high) algorithm and a hybrid iterative reconstruction (IR) algorithm ASiR-V50% (AV50) were explored, varying one at a time. To assess the effect of non-linear modifications of images by AV50 and DLIR-high, images of the water phantom were also reconstructed using filtered back projection (FBP). Quantitative measures of IQR, CV and SD were extracted from twelve pre-selected, circular (1 cm diameter) regions of interest (ROIs) capturing different texture patterns across all scans. RESULTS: Across all scans, imaging, and reconstruction settings, CV, IQR and SD were observed to increase with reduction in dose and slice thickness. An exception to this observation was found when using FBP reconstruction. Lower values of CV, IQR and SD were observed in DLIR-high reconstructions compared to AV50 and FBP. The Poisson statistics were more stringently noted in FBP than DLIR-high and AV50, due to the non-linear nature of the latter two algorithms. CONCLUSION: Variation in image noise due to dose reduction algorithms, tube current, and slice thickness show a consistent trend across phantom and patient scans. Prospective evaluation across multiple centers, scanners and imaging protocols is needed for establishing quality assurance standards of radiomics.

A magnetic hydrogel for the efficient retrieval of kidney stone fragments during ureteroscopy.

Only 60-75% of conventional kidney stone surgeries achieve complete stone-free status. Up to 30% of patients with residual fragments <2 mm in size experience subsequent stone-related complications. Here we demonstrate a stone retrieval technology in which fragments are rendered magnetizable with a magnetic hydrogel so that they can be easily retrieved with a simple magnetic tool. The magnetic hydrogel facilitates robust in vitro capture of stone fragments of clinically relevant sizes and compositions. The hydrogel components exhibit no cytotoxicity in cell culture and only superficial effects on ex vivo human urothelium and in vivo mouse bladders. Furthermore, the hydrogel demonstrates antimicrobial activity against common uropathogens on par with that of common antibiotics. By enabling the efficient retrieval of kidney stone fragments, our method can lead to improved stone-free rates and patient outcomes.

Towards high reliability in national pathology education: Evaluating the United States and Canadian Academy of Pathology educational product.

The United States and Canadian Academy of Pathology (USCAP) leadership undertook a high level, global review of educational product outcomes data using high reliability organization (HRO) principles: preoccupation with failure; reluctance to simplify; sensitivity to operations; commitment to resilience; and deference to expertise. HRO principles have long been applied to fields such as aviation, nuclear power, and more recently to healthcare, yet they are rarely applied to the field that underpins these-and many other-complex systems: education. While errors in education are less calamitous than in air travel or healthcare delivery, USCAP's educational products impact over 15,000 learners a year, and thus have important implications for the future practice of pathology. Here we report USCAP's experiences using HRO principles to evaluate our keystone educational product, the "USCAP Short Course." Following this novel method of data review, USCAP leadership was able to better understand diverse learner needs based on practice venue, training level, and course topic. Unexpected lessons included the identification of specifically challenging educational topics, such as molecular pathology, and a need to focus more resources on emerging fields such as quality and patient safety. The results allow USCAP to assess educational product performance using HRO tools, and provide strong data-driven decision support for future national pathology education strategy.

Quality of life and lifetime achievement in adult survivors of pediatric heart transplant.

BACKGROUND: Survival in pediatric heart transplantation has improved since the first successful transplant over 35 years ago leading to increasing numbers of patients entering adulthood. We sought to examine quality of life and various lifetime achievements in our institutional population of long-term adult survivors of pediatric heart transplant. METHODS: Participants ≥18 years of age who received a heart transplant as a pediatric patient (<18 years old), and who have survived ≥10 years post-transplant, completed two self-report surveys: (1) Ferrans and Powers QLI cardiac version which reports a measure of life satisfaction with a range of 0 (very dissatisfied) to 1 (very satisfied); and (2) CHONY Pediatric Heart Transplant Life Achievement Survey to examine lifetime achievement. RESULTS: Sixty-two and sixty-five participants completed the Ferrans and Powers QLI cardiac version and CHONY Pediatric Heart Transplant Life Achievement Survey. The mean overall QLI was 0.75 ± 0.14 with the most satisfaction in the family domain. QLI scores were analyzed by age at initial transplant, gender, indication for transplant, and whether patients currently followed by pediatric or adult providers, with no statistically significant differences noted. Seventy-two percent of participants demonstrated stable employment or schooling. Around thirty percent of participants showed the ability to reach academic milestones including college and post-graduate education and ten percent to start their own families. CONCLUSIONS: Our cohort of long-term adult survivors of pediatric heart transplant report a quality of life with scores thought to be reflective of a satisfactory quality of life, and many demonstrate achievement of major life milestones.

Randomized controlled trial investigating use of submucosal injection of EverLift™ in rates of complete resection of non-pedunculated 4-9 mm polyps.

INTRODUCTION: Currently, cold snare polypectomy (CSP) without submucosal injection is recommended for removing polyps < 10 mm. Use of viscous submucosal agents has not been previously evaluated in CSP. We investigate the potential role of EverLift™ (GI Supply, Pennsylvania) in CSP. METHODS: The study is a single-center prospective randomized non-inferiority clinical trial evaluating CSP of non-pedunculated 4-9 mm polyps, with or without submucosal injection of EverLift™. Patients 18-80 years of age presenting for colonoscopy were recruited. Eligible polyps underwent block randomization to CSP with or without EverLift™. Following CSP, two biopsies were performed at the CSP site margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies (non-inferiority margin -10%). RESULTS: A total of 291 eligible polyps underwent CSP, with 142 removed using EverLift™. There was similar polyp size and distribution of pathology between the two groups. Overall, there was a low rate of positive margins with (1.4%) or without submucosal injection (2.8%), with no significant difference in complete resection (difference 1.28%, 95% CI: -2.66 to 5.42%), demonstrating non-inferiority of EverLift™ injection. Use of EverLift™ significantly increased CSP time (109.8 vs 38.8 s, p < 0.0001) and frequency of use of hemostatic clips (13.4 vs 3.6%, p = 0.002). CONCLUSION: Submucosal injection of EverLift™ was non-inferior to CSP of 4-9 mm polyps without injection and increased time for resection as well as use of hemostatic clips to control acute bleeding. Our results suggest that polypectomy of 4-9 mm polyps can be safely performed without submucosal injection of EverLift™.

Randomized Controlled Trial Investigating Cold Snare and Forceps Polypectomy Among Small POLYPs in Rates of Complete Resection: The TINYPOLYP Trial.

INTRODUCTION: Optimizing complete resection during colonoscopy is important because residual neoplastic tissue may play a role in interval cancers. The US Multi-Society Task Force recommends diminutive (≤5 mm) and small (6-9 mm) polyps be removed by cold snare polypectomy (CSP). However, evidence is less clear whether CSP retains significant advantage over cold forceps polypectomy (CFP) for polyps ≤3 mm. METHODS: This study is a single-center prospective noninferiority randomized clinical trial evaluating CFP and CSP for nonpedunculated polyps ≤3 mm. Patients 18 years and older undergoing colonoscopy for any indication were recruited. During each colonoscopy, polyps underwent block randomization to removal with CFP or CSP. After polypectomy, 2 biopsies were taken from the polypectomy margin. The primary noninferiority outcome was the complete resection rate, defined by absence of residual polyp in the margin biopsies. RESULTS: A total of 179 patients were included. Patients had similar distribution in age, sex, race/ethnicity, as well as indication of procedure. A total of 279 polyps ≤3 mm were identified, with 138 in the CSP group and 141 in the CFP group. Mean polypectomy time was longer for CSP compared with CFP (42.3 vs 23.2 seconds, P < 0.001), although a higher proportion of polyps removed by CFP were removed in more than 1 piece compared with CSP (15.6 vs 3.6%, P < 0.001). There were positive margin biopsies in 2 cases per cohort, with a complete resection rate of 98.3% in both groups. There was no significant difference in cohorts in complete resection rates (difference in complete resection rates was 0.057%, 95% confidence interval: -4.30% to 4.53%), demonstrating noninferiority of CFP compared with CSP. DISCUSSION: Use of CFP was noninferior to CSP in the complete resection of nonpedunculated polyps ≤3 mm. CSP required significantly more time to perform compared with CFP. CFP should be considered an acceptable alternative to CSP for removal of polyps ≤3 mm.

Low-contrast detectability and potential for radiation dose reduction using deep learning image reconstruction-A 20-reader study on a semi-anthropomorphic liver phantom.

Background: A novel deep learning image reconstruction (DLIR) algorithm for CT has recently been clinically approved. Purpose: To assess low-contrast detectability and dose reduction potential for CT images reconstructed with the DLIR algorithm and compare with filtered back projection (FBP) and hybrid iterative reconstruction (IR). Material and methods: A customized upper-abdomen phantom containing four cylindrical liver inserts with low-contrast lesions was scanned at CT dose indexes of 5, 10, 15, 20 and 25 mGy. Images were reconstructed with FBP, 50% hybrid IR (IR50), and DLIR of low strength (DLL), medium strength (DLM) and high strength (DLH). Detectability was assessed by 20 independent readers using a two-alternative forced choice approach. Dose reduction potential was estimated separately for each strength of DLIR using a fitted model, with the detectability performance of FBP and IR50 as reference. Results: For the investigated dose levels of 5 and 10 mGy, DLM improved detectability compared to FBP by 5.8 and 6.9 percentage points (p.p.), and DLH improved detectability by 9.6 and 12.3 p.p., respectively (all p < .007). With IR50 as reference, DLH improved detectability by 5.2 and 9.8 p.p. for the 5 and 10 mGy dose level, respectively (p < .03). With respect to this low-contrast detectability task, average dose reduction potential relative to FBP was estimated to 39% for DLM and 55% for DLH. Relative to IR50, average dose reduction potential was estimated to 21% for DLM and 42% for DLH. Conclusions: Low-contrast detectability performance is improved when applying a DLIR algorithm, with potential for radiation dose reduction.

A Prospective Trial of an In-house Overnight Fellow Rotation in the Intensive Care Unit.

Background: Although previous studies in academic intensive care units (ICUs) have found no improvement in patient care outcomes with in-house overnight attending physician coverage compared with home call coverage, the effect of in-house supervision on trainee education and well-being is less clear. In addition, no studies have examined the effect of in-house coverage by fellow physicians overnight. Objective: What is the impact of an in-house overnight critical care fellow on resident, fellow, and attending perception of patient safety, house staff education, and house staff well-being? Methods: A prospective trial alternating 2-week periods of in-house overnight critical care fellow coverage with 2-week periods of home call coverage was performed in our tertiary medical ICU. Residents, fellows, and attendings were surveyed to evaluate perceptions of the night fellows' impact on patient care, communication, supervision, educational experience, autonomy, well-being, and job satisfaction. Results: Over the 6-month study period, surveys were sent to 83 residents, 22 fellows, and 23 attendings, with completion by 56 (67%), 22 (100%), and 16 (70%), respectively. Overall, 89% of residents, 68% of fellows, and 81% of attendings reported perceived improvements in patient care with an in-house fellow. The in-house fellow was also associated with improved well-being in 79% of residents and 73% of fellows, and 82% of residents felt that it positively impacted education. Conclusion: As compared with the traditional home call system, an in-house night critical care fellow can improve the perception of patient care, trainee well-being, and education in a tertiary ICU at an academic hospital.

Iterative reconstruction improves image quality and reduces radiation dose in trauma protocols; A human cadaver study.

BACKGROUND: Radiation-related cancer risk is an object of concern in CT of trauma patients, as these represent a young population. Different radiation reducing methods, including iterative reconstruction (IR), and spilt bolus techniques have been introduced in the recent years in different large scale trauma centers. PURPOSE: To compare image quality in human cadaver exposed to thoracoabdominal computed tomography using IR and standard filtered back-projection (FBP) at different dose levels. MATERIAL AND METHODS: Ten cadavers were scanned at full dose and a dose reduction in CTDIvol of 5 mGy (low dose 1) and 7.5 mGy (low dose 2) on a Siemens Definition Flash 128-slice computed tomography scanner. Low dose images were reconstructed with FBP and Sinogram affirmed iterative reconstruction (SAFIRE) level 2 and 4. Quantitative image quality was analyzed by comparison of contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). Qualitative image quality was evaluated by use of visual grading regression (VGR) by four radiologists. RESULTS: Readers preferred SAFIRE reconstructed images over FBP at a dose reduction of 40% (low dose 1) and 56% (low dose 2), with significant difference in overall impression of image quality. CNR and SNR showed significant improvement for images reconstructed with SAFIRE 2 and 4 compared to FBP at both low dose levels. CONCLUSIONS: Iterative image reconstruction, SAFIRE 2 and 4, resulted in equal or improved image quality at a dose reduction of up to 56% compared to full dose FBP and may be used a strong radiation reduction tool in the young trauma population.

Quantitative benchmarking of iodine imaging for two CT spectral imaging technologies: a phantom study.

BACKGROUND: The aim of this study was to quantitatively benchmark iodine imaging across specific virtual monoenergetic energy levels, iodine maps and virtual non-contrast images with different phantom sizes and iodine concentrations, using a rapid switching dual-energy CT (DECT) and a dual source DECT, in order to investigate accuracy and potential differences between the technologies. METHODS: Solutions of iodine contrast (10, 20, 30, 50, and 100 mg/mL), sterile water and saline were scanned in a phantom on a rapid switching single-source and dual-source DECT scanners from two different vendors. The phantom was equipped with polyurethane rings simulating three body sizes. The datasets were reconstructed in virtual monoenergetic energy levels (70, 80, 90, 100, 110, 120, 130, and 140 keV), virtual non-contrast images and iodine maps. HU and iodine concentrations were measured by placing ROIs in the iodine solutions. RESULTS: The iodine concentrations were reproduced with a high degree of accuracy for the single-source DECT (1.8-9.0%), showing a slight dependence on phantom size. The dual source DECT technique showed deviant values (error -33.8 to 12.0%) for high concentrations. In relation to the virtual non-contrast measurements, the images from both vendors were affected by the iodine concentration and phantom size (-127.8 to 539.1 HU). Phantom size did not affect the calculated monoenergetic attenuation values, but the attenuation values varied between the scanners. CONCLUSIONS: Quantitative measurements of post-processed images are dependent on the concentration of iodine, the phantom size and different technologies. However, our study indicates that the iodine maps are reliable for quantification of iodine.

Implementation of Collection of Patients' Disability Status by Centralized Scheduling.

BACKGROUND: Collection of disability status in electronic health records (EHRs) is critical to addressing the significant health care disparities experienced by patients with disabilities. Despite this, little evidence exists to inform implementation. METHODS: This pilot trial evaluated the implementation of collection of patients' disability status during primary care new patient registration by centralized call center staff. The study took place over six weeks at an academic hospital system in Colorado. Staff received a 30-minute training on how to ask and document disability status in the EHR. Completion rate of collection, fidelity, and concordance were assessed through chart reviews and recordings of patient registration calls. Focus groups with staff and phone interviews with patients assessed the experience of including disability screeners in patient registration. RESULTS: A total of 3,673 new patients were registered at one of the 53 primary care clinics during the study period. Completion of disability status in the EHR increased from 9.5% at baseline to 53.5% by the last week of the trial, which was then maintained for eight weeks. Challenges were identified in the recorded calls with fidelity of if and how the questions were asked. No patient complaints were reported, and patients reported no concerns regarding collection of disability status during interviews. CONCLUSION: Documenting disability status during patient registration was effective and was not concerning to patients. To make initial steps to providing equitable care, efforts should be made to implement this type of screening universally across the clinical encounter.

Predictors of Receipt of Clinical Preventive Services in Adolescents and Adults with Down Syndrome Accessing Medicaid.

BACKGROUND: Persons with Down syndrome (DS) require preventive care that addresses their age-/gender- and syndrome-specific needs. Yet, adolescents and adults with DS do not receive these preventive care services as recommended. OBJECTIVE/HYPOTHESIS: To identify factors that predict receipt of age-/gender- and syndrome-specific preventive healthcare among adolescents and adults with DS. We hypothesized that more healthcare encounters and greater medical complexity would increase receipt of preventive care due to more opportunities to complete these activities. METHODS: Using Medicaid claims (2006-2010) for California, Colorado, Michigan, and Pennsylvania, we conducted a retrospective cohort study of adolescents and adults with DS (≥12 years old). We modeled receipt of both ≥1 wellness examination and ≥1 thyroid function test (TFT) in 2009-2010 as a function of receipt of those same healthcare activities in 2006-08, adjusting for demographics, key comorbidities, and medical complexity using multivariable logistic regression. RESULTS: In this cohort of 3487 adolescents and adults with DS accessing Medicaid, 17% received both ≥1 wellness examination and ≥1 TFT in 2006-2008, 15% in 2009-2010, and only 7% during both time periods. Despite medical complexity and frequent healthcare interactions, the best predictor of future receipt of these activities was past receipt. State of residence variably impacted receipt of these preventive activities. CONCLUSIONS: Although past receipt of wellness examination and TFT was the best predictor of future receipt of these activities, overall rates were quite low in this cohort of adolescents and adults with DS. Further work is needed to improve preventive healthcare delivery to this vulnerable population.

Low Rates of Preventive Healthcare Service Utilization Among Adolescents and Adults With Down Syndrome.

INTRODUCTION: People with Down syndrome have health risks that require specific lifelong preventive health care. With increasing life expectancy, people with Down syndrome also face health conditions typical of their unaffected peers and thus need coordinated health care. The purpose of this study is to describe rates of age/sex- and Down syndrome-specific preventive healthcare activities among adolescents and adults with Down syndrome. METHODS: Using Medicaid claims (2006-2010) in California, Colorado, Michigan, and Pennsylvania, the cohort was defined as people with Down syndrome aged ≥12 years seen by primary care providers and enrolled in Medicaid for ≥45 of 60 months without dual Medicare enrollment (n=3,501). Age focus-consistent primary care providers were defined as having a focus concordant with a patient's age: 12-17 years, child or mixed-focus; ≥26 years, adult or mixed-focus; 18-25 years, any focus. Differences in healthcare activities were evaluated using Pearson's chi-square, Fisher's exact, and Kruskal-Wallis tests. Analyses were performed in 2015-2017. RESULTS: Of the cohort, 79% had an age focus-consistent primary care provider. However, 40% of adults aged ≥26 years received care from a child-focused primary care provider. Only 43% with an age focus-consistent provider had ≥1 well examination (age focus-inconsistent primary care provider: 35%, p<0.001). Most preventive activities had poor rates (<50%) regardless of age focus consistency between provider and patient age or whether they were age/sex- or Down syndrome-specific (well examinations; vaccinations; sleep apnea; hearing; and breast, cervical, and colon cancer screenings). Lipids, vision, and thyroid screenings reached moderate levels (50% to <80%). CONCLUSIONS: Rates of age/sex- and Down syndrome-specific preventive recommendations were low among adolescents and adults with Down syndrome, regardless of the age focus consistency of their primary care provider. This represents a significant opportunity to improve primary care in this vulnerable population.

BENCHMARKING OF A NEW AUTOMATIC CT RADIATION DOSE CALCULATOR.

Information on patient radiation dose is essential to meet the radiation protection regulations and the demands of dose optimization. Vendors have developed different tools for patient dose assessment for radiological purposes. In this study, estimated effective doses derived from a new image-based software tool (DoseWatch, GE Healthcare) was benchmarked against the corresponding doses from a dose calculator (CT-Expo, SASCRAD) and a conversion coefficient method. Dose data from 150 adult patients (66 male and 84 female), who underwent CT head, abdominopelvic or chest examinations, were retrospectively collected using DoseWatch. Effective dose estimated by DoseWatch was significantly lower than that of CT-Expo and DLP-E (k) (p ≤ 0.001). For the organ doses, DoseWatch resulted in lower dose than CT-Expo for all the organs with the exception of testis (p ≤ 001) and eye lenses (p ≤ 0.026).

Evaluation of Image Quality for 7 Iterative Reconstruction Algorithms in Chest Computed Tomography Imaging: A Phantom Study.

OBJECTIVES: This study aimed to evaluate the image quality of 7 iterative reconstruction (IR) algorithms in comparison to filtered back-projection (FBP) algorithm. METHODS: An anthropomorphic chest phantom was scanned on 4 computed tomography scanners and reconstructed with FBP and IR algorithms. Image quality of anatomical details-large/medium-sized pulmonary vessels, small pulmonary vessels, thoracic wall, and small and large lesions-was scored. Furthermore, general impression of noise, image contrast, and artifacts were evaluated. Visual grading regression was used to analyze the data. Standard deviations were measured, and the noise power spectrum was calculated. RESULTS: Iterative reconstruction algorithms showed significantly better results when compared with FBP for these criteria (regression coefficients/P values in parentheses): vessels (FIRST: -1.8/0.05, AIDR Enhanced: <-2.3/0.01, Veo: <-0.1/0.03, ADMIRE: <-2.1/0.04), lesions (FIRST: <-2.6/0.01, AIDR Enhanced: <-1.9/0.03, IMR1: <-2.7/0.01, Veo: <-2.4/0.02, ADMIRE: -2.3/0.02), image noise (FIRST: <-3.2/0.004, AIDR Enhanced: <-3.5/0.002, IMR1: <-6.1/0.001, iDose: <-2.3/0.02, Veo: <-3.4/0.002, ADMIRE: <-3.5/0.02), image contrast (FIRST: -2.3/0.01, AIDR Enhanced: -2.5/0.01, IMR1: -3.7/0.001, iDose: -2.1/0.02), and artifacts (FIRST: <-3.8/0.004, AIDR Enhanced: <-2.7/0.02, IMR1: <-2.6/0.02, iDose: -2.1/0.04, Veo: -2.6/0.02). The iDose algorithm was the only IR algorithm that maintained the noise frequencies. CONCLUSIONS: Iterative reconstruction algorithms performed differently on all evaluated criteria, showing the importance of careful implementation of algorithms for diagnostic purposes.

Molecular profiling of a primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid.

Primary cutaneous signet-ring cell/histiocytoid carcinoma of the eyelid is a rare and aggressive neoplasm. Fewer than 50 cases have been reported in the literature, and the genetic driving mutations are unknown. Herein, we present a case of this rare disease along with the results of molecular profiling via targeted next-generation sequencing. The patient is an 85-year-old man who presented with left eyelid swelling initially thought to be a chalazion. After no response to incision and drainage and antibiotics, an incisional biopsy was performed. Histopathologic sections revealed a proliferation of cells with signet-ring and histiocytoid morphology arranged singly and in cords infiltrating the dermis, subcutaneous tissue, and muscle. The lesional cells strongly expressed cytoplasmic cytokeratin 7 and nuclear androgen receptor. Next-generation sequencing revealed a CDH1 mutation, which is known to confer signet-ring morphology in other carcinomas. Pathogenic mutations in NTRK3, CDKN1B, and PIK3CA were also detected. To our knowledge, this is the first documented genetic analysis of this rare disease with findings that offer insights into disease pathogenesis and potential therapeutic targets.

Integrating genomic features for non-invasive early lung cancer detection.

Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.