Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency.

The p110δ subunit of phosphatidylinositol-3-OH kinase (PI(3)K) is selectively expressed in leukocytes and is critical for lymphocyte biology. Here we report fourteen patients from seven families who were heterozygous for three different germline, gain-of-function mutations in PIK3CD (which encodes p110δ). These patients presented with sinopulmonary infections, lymphadenopathy, nodular lymphoid hyperplasia and viremia due to cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV). Strikingly, they had a substantial deficiency in naive T cells but an over-representation of senescent effector T cells. In vitro, T cells from patients exhibited increased phosphorylation of the kinase Akt and hyperactivation of the metabolic checkpoint kinase mTOR, enhanced glucose uptake and terminal effector differentiation. Notably, treatment with rapamycin to inhibit mTOR activity in vivo partially restored the abundance of naive T cells, largely 'rescued' the in vitro T cell defects and improved the clinical course.

Rethinking Clinical Trial Radiology Workflows and Student Training: Integrated Virtual Student Shadowing Experience, Education, and Evaluation.

There is consistent demand for clinical exposure from students interested in radiology; however, the COVID-19 pandemic resulted in fewer available options and limited student access to radiology departments. Additionally, there is increased demand for radiologists to manage more complex quantification in reports on patients enrolled in clinical trials. We present an online educational curriculum that addresses both of these gaps by virtually immersing students (radiology preprocessors, or RPs) into radiologists' workflows where they identify and measure target lesions in advance of radiologists, streamlining report quantification. RPs switched to remote work at the beginning of the COVID-19 pandemic in our National Institutes of Health (NIH). We accommodated them by transitioning our curriculum on cross-sectional anatomy and advanced PACS tools to a publicly available online curriculum. We describe collaborations between multiple academic research centers and industry through contributions of academic content to this curriculum. Further, we describe how we objectively assess educational effectiveness with cross-sectional anatomical quizzes and decreasing RP miss rates as they gain experience. Our RP curriculum generated significant interest evidenced by a dozen academic and research institutes providing online presentations including radiology modality basics and quantification in clinical trials. We report a decrease in RP miss rate percentage, including one virtual RP over a period of 1 year. Results reflect training effectiveness through decreased discrepancies with radiologist reports and improved tumor identification over time. We present our RP curriculum and multicenter experience as a pilot experience in a clinical trial research setting. Students are able to obtain useful clinical radiology experience in a virtual learning environment by immersing themselves into a clinical radiologist's workflow. At the same time, they help radiologists improve patient care with more valuable quantitative reports, previously shown to improve radiologist efficiency. Students identify and measure lesions in clinical trials before radiologists, and then review their reports for self-evaluation based on included measurements from the radiologists. We consider our virtual approach as a supplement to student education while providing a model for how artificial intelligence will improve patient care with more consistent quantification while improving radiologist efficiency.

Gamification in Radiology Training Module Developed During the Society for Imaging Informatics in Medicine Annual Meeting Hackathon.

The purpose of this manuscript is to report our experience in the 2021 SIIM Virtual Hackathon, where we developed a proof-of-concept of a radiology training module with elements of gamification. In the 50 h allotted in the hackathon, we proposed an idea, connected with colleagues from five different countries, and completed an operational proof-of-concept, which was demonstrated live at the hackathon showcase, competing with eight other teams. Our prototype involved participants annotating publicly available chest radiographs of patients with tuberculosis. We showed how we could give experience points to trainees based on annotation precision compared to ground truth radiologists' annotation, ranked in a live leaderboard. We believe that gamification elements could provide an engaging solution for radiology education. Our project was awarded first place out of eight participating hackathon teams.

Interactive Multimedia Reporting Technical Considerations: HIMSS-SIIM Collaborative White Paper.

Despite technological advances in the analysis of digital images for medical consultations, many health information systems lack the ability to correlate textual descriptions of image findings linked to the actual images. Images and reports often reside in separate silos in the medical record throughout the process of image viewing, report authoring, and report consumption. Forward-thinking centers and early adopters have created interactive reports with multimedia elements and embedded hyperlinks in reports that connect the narrative text with the related source images and measurements. Most of these solutions rely on proprietary single-vendor systems for viewing and reporting in the absence of any encompassing industry standards to facilitate interoperability with the electronic health record (EHR) and other systems. International standards have enabled the digitization of image acquisition, storage, viewing, and structured reporting. These provide the foundation to discuss enhanced reporting. Lessons learned in the digital transformation of radiology and pathology can serve as a basis for interactive multimedia reporting (IMR) across image-centric medical specialties. This paper describes the standard-based infrastructure and communications to fulfill recently defined clinical requirements through a consensus from an international workgroup of multidisciplinary medical specialists, informaticists, and industry participants. These efforts have led toward the development of an Integrating the Healthcare Enterprise (IHE) profile that will serve as a foundation for interoperable interactive multimedia reporting.

Collaborative Writing Projects: Set Yourself up for Success.

ABSTRACT: This article will review critical components for the successful completion of a multi-institution, multiauthor collaborative paper. Best practices for the creation and publication of a collaborative paper will be addressed.

Multispecialty Enterprise Imaging Workgroup Consensus on Interactive Multimedia Reporting Current State and Road to the Future: HIMSS-SIIM Collaborative White Paper.

Diagnostic and evidential static image, video clip, and sound multimedia are captured during routine clinical care in cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, endoscopic procedural specialties, and other medical disciplines. Providers typically describe the multimedia findings in contemporaneous electronic health record clinical notes or associate a textual interpretative report. Visual communication aids commonly used to connect, synthesize, and supplement multimedia and descriptive text outside medicine remain technically challenging to integrate into patient care. Such beneficial interactive elements may include hyperlinks between text, multimedia elements, alphanumeric and geometric annotations, tables, graphs, timelines, diagrams, anatomic maps, and hyperlinks to external educational references that patients or provider consumers may find valuable. This HIMSS-SIIM Enterprise Imaging Community workgroup white paper outlines the current and desired clinical future state of interactive multimedia reporting (IMR). The workgroup adopted a consensus definition of IMR as "interactive medical documentation that combines clinical images, videos, sound, imaging metadata, and/or image annotations with text, typographic emphases, tables, graphs, event timelines, anatomic maps, hyperlinks, and/or educational resources to optimize communication between medical professionals, and between medical professionals and their patients." This white paper also serves as a precursor for future efforts toward solving technical issues impeding routine interactive multimedia report creation and ingestion into electronic health records.

Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial.

BACKGROUND: Cabozantinib is a multikinase inhibitor of MET, VEGFR, AXL, and RET, which also has an effect on the tumour immune microenvironment by decreasing regulatory T cells and myeloid-derived suppressor cells. In this study, we examined the activity of cabozantinib in patients with metastatic platinum-refractory urothelial carcinoma. METHODS: This study was an open-label, single-arm, three-cohort phase 2 trial done at the National Cancer Institute (Bethesda, MD, USA). Eligible patients were 18 years or older, had histologically confirmed urothelial carcinoma or rare genitourinary tract histologies, Karnofsky performance scale index of 60% or higher, and documented disease progression after at least one previous line of platinum-based chemotherapy (platinum-refractory). Cohort one included patients with metastatic urothelial carcinoma with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Two additional cohorts that enrolled in parallel (patients with bone-only urothelial carcinoma metastases and patients with rare histologies of the genitourinary tract) were exploratory. Patients received cabozantinib 60 mg orally once daily in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate by RECIST in cohort one. Response was assessed in all patients who met the eligibility criteria and who received at least 8 weeks of therapy. All patients who received at least one dose of cabozantinib were included in the safety analysis. This completed study is registered with ClinicalTrials.gov, NCT01688999. FINDINGS: Between Sept 28, 2012, and Oct, 20, 2015, 68 patients were enrolled on the study (49 in cohort one, six in cohort two, and 13 in cohort three). All patients received at least one dose of cabozantinib. The median follow-up was 61·2 months (IQR 53·8-70·0) for the 57 patients evaluable for response. In the 42 evaluable patients in cohort one, there was one complete response and seven partial responses (objective response rate 19%, 95% CI 9-34). The most common grade 3-4 adverse events were fatigue (six [9%] patients), hypertension (five [7%]), proteinuria (four [6%]), and hypophosphataemia (four [6%]). There were no treatment-related deaths. INTERPRETATION: Cabozantinib has single-agent clinical activity in patients with heavily pretreated, platinum-refractory metastatic urothelial carcinoma with measurable disease and bone metastases and is generally well tolerated. Cabozantinib has innate and adaptive immunomodulatory properties providing a rationale for combining cabozantinib with immunotherapeutic strategies. FUNDING: National Cancer Institute Intramural Program and the Cancer Therapy Evaluation Program.

CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis.

BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients' cells, which we confirmed by means of exogenous induction of expression of CD55. RESULTS: We identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients' T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation. CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Preparing Medical Imaging Data for Machine Learning.

Artificial intelligence (AI) continues to garner substantial interest in medical imaging. The potential applications are vast and include the entirety of the medical imaging life cycle from image creation to diagnosis to outcome prediction. The chief obstacles to development and clinical implementation of AI algorithms include availability of sufficiently large, curated, and representative training data that includes expert labeling (eg, annotations). Current supervised AI methods require a curation process for data to optimally train, validate, and test algorithms. Currently, most research groups and industry have limited data access based on small sample sizes from small geographic areas. In addition, the preparation of data is a costly and time-intensive process, the results of which are algorithms with limited utility and poor generalization. In this article, the authors describe fundamental steps for preparing medical imaging data in AI algorithm development, explain current limitations to data curation, and explore new approaches to address the problem of data availability.

Web-based Conferencing: Tips, Tricks, and Scenario-based Best Practices for Clinicians During a Pandemic Crisis.

This article will familiarize the reader with useful tools and trouble-shooting tips for web-based conferencing. Radiology-based scenarios for web conferencing are also provided.

Cumulative Radiation Exposures from CT Screening and Surveillance Strategies for von Hippel-Lindau-associated Solid Pancreatic Tumors.

Purpose To assess the potential ionizing radiation exposure from CT scans for both screening and surveillance of patients with von Hippel-Lindau (VHL) syndrome. Materials and Methods For this retrospective study, abdomen-pelvic (AP) and chest-abdomen-pelvic (CAP) CT scans were performed with either a three-phase (n = 1242) or a dual-energy virtual noncontrast protocol (VNC; n = 149) in 747 patients with VHL syndrome in the National Institutes of Health Clinical Center between 2009 and 2015 (mean age, 47.6 years ± 14.6 [standard deviation]; age range, 12-83 years; 320 women [42.8%]). CT scanning parameters for patients with pancreatic neuroendocrine tumors (PNETs; 124 patients and 381 scans) were compared between a tumor diameter-based surveillance protocol and a VHL genotype and tumor diameter-based algorithm (a tailored algorithm) developed by three VHL clinicians. Organ and lifetime radiation doses were estimated by two radiologists and five radiation scientists. Cumulative radiation doses were compared between the PNET surveillance algorithms by analyses of variance, and a two-tailed P value less than .05 indicated statistical significance. Results Median cumulative colon doses for annual CAP and AP CT scans from age 15 to 40 years ranged from 0.34 Gy (5th-95th percentiles, 0.18-0.75; dual-energy VNC CT) to 0.89 Gy (5th-95th percentiles, 0.42-1.0; three-phase CT). For the current PNET surveillance protocol, the cumulative effective radiation dose from age 40 to 65 years was 682 mSv (tumors < 1.2 cm) and 2125 mSv (tumors > 3 cm). The tailored algorithm could halve these doses for patients with initial tumor diameter less than 1.2 cm (P < .001). Conclusion CT screening of patients with von Hippel-Lindau syndrome can lead to substantial radiation exposures, even with dual-energy virtual noncontrast CT. A genome and tumor diameter-based algorithm for pancreatic neuroendocrine tumor surveillance may potentially reduce lifetime radiation exposure. © RSNA, 2018 Online supplemental material is available for this article.

Automatic Mapping of CT Scan Locations on Computational Human Phantoms for Organ Dose Estimation.

To develop an algorithm to automatically map CT scan locations of patients onto computational human phantoms to provide with patient-specific organ doses. We developed an algorithm that compares a two-dimensional skeletal mask generated from patient CTs with that of a whole body computational human phantom. The algorithm selected the scan locations showing the highest Dice Similarity Coefficient (DSC) calculated between the skeletal masks of a patient and a phantom. To test the performance of the algorithm, we randomly selected five sets of neck, chest, and abdominal CT images from the National Institutes of Health Clinical Center. We first automatically mapped scan locations of the CT images on a computational human phantom using our algorithm. We had several radiologists to manually map the same CT images on the phantom and compared the results with the automated mapping. Finally, organ doses for automated and manual mapping locations were calculated by an in-house CT dose calculator and compared to each other. The visual comparison showed excellent agreement between manual and automatic mapping locations for neck, chest, and abdomen-pelvis CTs. The difference in mapping locations averaged over the start and end in the five patients was less than 1 cm for all neck, chest, and AP scans: 0.9, 0.7, and 0.9 cm for neck, chest, and AP scans, respectively. Five cases out of ten in the neck scans show zero difference between the average manual and automatic mappings. Average of absolute dose differences between manual and automatic mappings was 2.3, 2.7, and 4.0% for neck, chest, and AP scans, respectively. The automatic mapping algorithm provided accurate scan locations and organ doses compared to manual mapping. The algorithm will be useful in cases requiring patient-specific organ dose for a large number of patients such as patient dose monitoring, clinical trials, and epidemiologic studies.

Lens Dose Reduction by Patient Posture Modification During Neck CT.

OBJECTIVE: Radiation exposure of the lens during neck CT may increase a patient's risk of developing cataracts. Radiologists at the National Institutes of Health worked with technicians to modify the neck CT scanning procedure to include a reduction in the scanning range, a reduction in the tube potential (kilovoltage), and a change in neck positioning using a head tilt. We objectively quantified the organ dose changes after this procedure modification using a computer simulation. MATERIALS AND METHODS: We retrospectively analyzed CT images of 40 patients (20 men and 20 women) scanned before and after the procedure change. Radiation dose to the lens delivered before and after the procedure change was calculated using an in-house CT dose calculator combined with computational human phantoms deformed to match head tilt angles. We also calculated the doses to other radiosensitive organs including the brain, pituitary gland, eye globes, and salivary glands before and after the procedure change. RESULTS: Our dose calculations showed that modifying the neck position, shortening the scanning range, and reducing the tube potential reduced the dose to the lens by 89% (p < 0.0001). The median brain, pituitary gland, globes, and salivary gland doses also decreased by 59%, 52%, 66%, and 29%, respectively. We found that overranging significantly affects the lens dose. CONCLUSION: Combining head tilt and scanning range reduction is an easy and effective method that significantly reduces radiation dose to the lens and other radiosensitive head and neck organs.

Multimedia-enhanced Radiology Reports: Concept, Components, and Challenges.

Multimedia-enhanced radiology report (MERR) development is defined and described from an informatics perspective, in which the MERR is seen as a superior information-communicating entity. Recent technical advances, such as the hyperlinking of report text directly to annotated images, improve MERR information content and accessibility compared with text-only reports. The MERR is analyzed by its components, which include hypertext, tables, graphs, embedded images, and their interconnections. The authors highlight the advantages of each component for improving the radiologist's communication of report content information and the user's ability to extract information. Requirements for MERR implementation (eg, integration of picture archiving and communication systems, radiology information systems, and electronic medical record systems) and the authors' initial experiences and challenges in MERR implementation at the National Institutes of Health are reviewed. The transition to MERRs has provided advantages over use of traditional text-only radiology reports because of the capacity to include hyperlinked report text that directs clinicians to image annotations, images, tables, and graphs. A framework is provided for thinking about the MERR from the user's perspective. Additional applications of emerging technologies (eg, artificial intelligence and machine learning) are described in the crafting of what the authors believe is the radiology report of the future. ©RSNA, 2018.

Feasibility of Dose-reduced Chest CT with Photon-counting Detectors: Initial Results in Humans.

Purpose To investigate whether photon-counting detector (PCD) technology can improve dose-reduced chest computed tomography (CT) image quality compared with that attained with conventional energy-integrating detector (EID) technology in vivo. Materials and Methods This was a HIPAA-compliant institutional review board-approved study, with informed consent from patients. Dose-reduced spiral unenhanced lung EID and PCD CT examinations were performed in 30 asymptomatic volunteers in accordance with manufacturer-recommended guidelines for CT lung cancer screening (120-kVp tube voltage, 20-mAs reference tube current-time product for both detectors). Quantitative analysis of images included measurement of mean attenuation, noise power spectrum (NPS), and lung nodule contrast-to-noise ratio (CNR). Images were qualitatively analyzed by three radiologists blinded to detector type. Reproducibility was assessed with the intraclass correlation coefficient (ICC). McNemar, paired t, and Wilcoxon signed-rank tests were used to compare image quality. Results Thirty study subjects were evaluated (mean age, 55.0 years ± 8.7 [standard deviation]; 14 men). Of these patients, 10 had a normal body mass index (BMI) (BMI range, 18.5-24.9 kg/m2; group 1), 10 were overweight (BMI range, 25.0-29.9 kg/m2; group 2), and 10 were obese (BMI ≥30.0 kg/m2, group 3). PCD diagnostic quality was higher than EID diagnostic quality (P = .016, P = .016, and P = .013 for readers 1, 2, and 3, respectively), with significantly better NPS and image quality scores for lung, soft tissue, and bone and with fewer beam-hardening artifacts (all P < .001). Image noise was significantly lower for PCD images in all BMI groups (P < .001 for groups 1 and 3, P < .01 for group 2), with higher CNR for lung nodule detection (12.1 ± 1.7 vs 10.0 ± 1.8, P < .001). Inter- and intrareader reproducibility were good (all ICC > 0.800). Conclusion Initial human experience with dose-reduced PCD chest CT demonstrated lower image noise compared with conventional EID CT, with better diagnostic quality and lung nodule CNR. © RSNA, 2017 Online supplemental material is available for this article.

Radiology Reports With Hyperlinks Improve Target Lesion Selection and Measurement Concordance in Cancer Trials.

OBJECTIVE: Radiology reports often lack the measurements of target lesions that are needed for oncology clinical trials. When available, the measurements in the radiology reports often do not match those in the records used to calculate therapeutic response. This study assessed the clinical value of hyperlinked tumor measurements in multimedia-enhanced radiology reports in the PACS and the inclusion of a radiologist assistant in the process of assessing tumor burden. MATERIALS AND METHODS: We assessed 489 target lesions in 232 CT examinations of 71 patients with metastatic genitourinary cancer enrolled in two therapeutic trials. We analyzed target lesion selection and measurement concordance between oncology records (used to calculate therapeutic response) and two types of radiology reports in the PACS: multimedia-enhanced radiology reports and text-only reports. For statistical tests, we used the Wilcoxon signed rank, Wilcoxon rank sum test, and Fisher method to combine p values from the paired and unpaired results. The Fisher exact test was used to compare overall measurement concordance. RESULTS: Concordance on target lesion selection was greater for multimedia-enhanced radiology reports (78%) than the text-only reports (52%) (p = 0.0050). There was also improved overall measurement concordance with the multimedia-enhanced radiology reports (68%) compared with the text-only reports (38%) (p < 0.0001). CONCLUSION: Compared with text-only reports, hyperlinked multimedia-enhanced radiology reports improved concordance of target lesion selection and measurement with the measurements used to calculate therapeutic response.

Clinical Applications of a CT Window Blending Algorithm: RADIO (Relative Attenuation-Dependent Image Overlay).

A methodology is described using Adobe Photoshop and Adobe Extendscript to process DICOM images with a Relative Attenuation-Dependent Image Overlay (RADIO) algorithm to visualize the full dynamic range of CT in one view, without requiring a change in window and level settings. The potential clinical uses for such an algorithm are described in a pictorial overview, including applications in emergency radiology, oncologic imaging, and nuclear medicine and molecular imaging.

ENABLE (Exportable Notation and Bookmark List Engine): an Interface to Manage Tumor Measurement Data from PACS to Cancer Databases.

Oncologists evaluate therapeutic response in cancer trials based on tumor quantification following selected "target" lesions over time. At our cancer center, a majority of oncologists use Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 quantifying tumor progression based on lesion measurements on imaging. Currently, our oncologists handwrite tumor measurements, followed by multiple manual data transfers; however, our Picture Archiving Communication System (PACS) (Carestream Health, Rochester, NY) has the ability to export tumor measurements, making it possible to manage tumor metadata digitally. We developed an interface, "Exportable Notation and Bookmark List Engine" (ENABLE), which produces prepopulated RECIST v1.1 worksheets and compiles cohort data and data models from PACS measurement data, thus eliminating handwriting and manual data transcription. We compared RECIST v1.1 data from eight patients (16 computed tomography exams) enrolled in an IRB-approved therapeutic trial with ENABLE outputs: 10 data fields with a total of 194 data points. All data in ENABLE's output matched with the existing data. Seven staff were taught how to use the interface with a 5-min explanatory instructional video. All were able to use ENABLE successfully without additional guidance. We additionally assessed 42 metastatic genitourinary cancer patients with available RECIST data within PACS to produce a best response waterfall plot. ENABLE manages tumor measurements and associated metadata exported from PACS, producing forms and data models compatible with cancer databases, obviating handwriting and the manual re-entry of data. Automation should reduce transcription errors and improve efficiency and the auditing process.

Abdominal Imaging with Contrast-enhanced Photon-counting CT: First Human Experience.

PURPOSE: To evaluate the performance of a prototype photon-counting detector (PCD) computed tomography (CT) system for abdominal CT in humans and to compare the results with a conventional energy-integrating detector (EID). MATERIALS AND METHODS: The study was HIPAA-compliant and institutional review board-approved with informed consent. Fifteen asymptomatic volunteers (seven men; mean age, 58.2 years ± 9.8 [standard deviation]) were prospectively enrolled between September 2 and November 13, 2015. Radiation dose-matched delayed contrast agent-enhanced spiral and axial abdominal EID and PCD scans were acquired. Spiral images were scored for image quality (Wilcoxon signed-rank test) in five regions of interest by three radiologists blinded to the detector system, and the axial scans were used to assess Hounsfield unit accuracy in seven regions of interest (paired t test). Intraclass correlation coefficient (ICC) was used to assess reproducibility. PCD images were also used to calculate iodine concentration maps. Spatial resolution, noise-power spectrum, and Hounsfield unit accuracy of the systems were estimated by using a CT phantom. RESULTS: In both systems, scores were similar for image quality (median score, 4; P = .19), noise (median score, 3; P = .30), and artifact (median score, 1; P = .17), with good interrater agreement (image quality, noise, and artifact ICC: 0.84, 0.88, and 0.74, respectively). Hounsfield unit values, spatial resolution, and noise-power spectrum were also similar with the exception of mean Hounsfield unit value in the spinal canal, which was lower in the PCD than the EID images because of beam hardening (20 HU vs 36.5 HU; P < .001). Contrast-to-noise ratio of enhanced kidney tissue was improved with PCD iodine mapping compared with EID (5.2 ± 1.3 vs 4.0 ± 1.3; P < .001). CONCLUSION: The performance of PCD showed no statistically significant difference compared with EID when the abdomen was evaluated in a conventional scan mode. PCD provides spectral information, which may be used for material decomposition.

Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations.

Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor αß(+) T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS. We report the natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relatives evaluated in our institution over the last 2 decades. Our principal findings are that FAS mutations have a clinical penetrance of <60%, elevated serum vitamin B12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortality in these patients are the overwhelming postsplenectomy sepsis and development of lymphoma. With longer follow-up, we observed a significantly greater relative risk of lymphoma than previously reported. Avoiding splenectomy while controlling hypersplenism by using corticosteroid-sparing treatments improves the outcome in ALPS-FAS patients. This trial was registered at www.clinicaltrials.gov as #NCT00001350.