Cladribine Use in Xanthoma Disseminatum: A Rare Case Presentation and Brief Updated Literature Review.

Xanthoma disseminatum (XD) is a rare, non-Langerhans cell histiocytosis. While treatment is notoriously difficult, 2-chlorodeoxyadenosine (cladribine) has recently emerged as a potential effective therapeutic option. Here, we describe the case of a 65-year-old male with XD who experienced significant cutaneous improvement after cladribine treatment. We also provide an updated literature review on cladribine use in patients with XD in light of reported adverse effects (AEs). While the efficacy of cladribine in XD is clear, no consensus exists for treatment duration and AE management. Hence, we strongly encourage interdisciplinary discourse involving dermatology and oncology in these cases.

Case report: Expanding the understanding of the adult polyglucosan body disease continuum: novel presentations, diagnostic pitfalls, and clinical pearls.

Introduction: Adult polyglucosan body disease (APBD) has long been regarded as the adult-onset form of glycogen storage disease type IV (GSD IV) and is caused by biallelic pathogenic variants in GBE1. Advances in the understanding of the natural history of APBD published in recent years have led to the use of discrete descriptors ("typical" versus "atypical") based on adherence to traditional symptomatology and homozygosity for the p.Y329S variant. Although these general descriptors are helpful in summarizing common findings and symptoms in APBD, they are inherently limited and may affect disease recognition in diverse populations. Methods: This case series includes three American patients (cases 1-3) and four Brazilian patients (cases 4-7) diagnosed with APBD. Patient-reported outcome (PRO) measures were employed to evaluate pain, fatigue, and quality of life in cases 1-3. Results: We describe the clinical course and diagnostic odyssey of seven cases of APBD that challenge the utility and efficacy of discrete descriptors. Cases 1-3 are compound heterozygotes that harbor the previously identified deep intronic variant in GBE1 and presented with "typical" APBD phenotypically, despite lacking two copies of the pathogenic p.Y329S variant. Patient-reported outcome measures in these three cases revealed the moderate levels of pain and fatigue as well as an impacted quality of life. Cases 4-7 have unique genotypic profiles and emphasize the growing recognition of presentations of APBD in diverse populations with broad neurological manifestations. Conclusion: Collectively, these cases underscore the understanding of APBD as a spectrum disorder existing on the GSD IV phenotypic continuum. We draw attention to the pitfalls of commonly used genetic testing methods when diagnosing APBD and highlight the utility of patient-reported outcome questionnaires in managing this disease.

Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease.

Historically, disease burden and treatment responses in patients with Gaucher disease (GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase (CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO is uninformative in patients heterozygous or homozygous for the CHIT1 c.1049_1072dup24 variant. Recently, glucosylsphingosine (lyso-Gb1), a sensitive and specific GD biomarker, has been recommended for patient monitoring. Furthermore, studies measuring lyso-Gb1 and CHITO in patients on long-term treatment with enzyme replacement therapy (ERT) and/or substrate reduction therapy (SRT) reported as group data show a reduction in both analytes, yet individualized patient data are generally unavailable. We describe seven patients on long-term treatment with longitudinal clinical data with monitoring based on current treatment guidelines. We present four patients who exhibit stable disease with normalized CHITO despite elevated lyso-Gb1. We present one patient who transitioned from ERT to SRT due to lack of a clinical response with life-threatening thrombocytopenia who responded with marked improvement in platelets, and normalized levels of both CHITO and lyso-Gb1. Finally, we present two ERT to SRT switch patients with stable disease on ERT who exhibited non-compliance on SRT, one with mirrored marked elevations of CHITO and lyso-Gb1; and another with normal CHITO and platelets, but increasing lyso-Gb1 levels and enlarged spleen. These clinical vignettes highlight the role of lyso-Gb1 as a sensitive biomarker in management of patients with GD, and its further value when CHITO is normal and thus uninformative. We highlight the personalized medicine approach needed to optimize treatment outcomes and recommendations for these patients.

Are Oblique Views Necessary? A Review of the Clinical Value of Oblique Knee Radiographs in the Acute Setting.

INTRODUCTION: The purpose of this study was to assess the added clinical value of oblique knee radiographs four-view (4V) compared to orthogonal anteroposterior (AP) and lateral radiographs in a two-view (2V) series. METHODS: We obtained 200 adult, 4V knee radiographs in 200 patients in the ED and randomly divided them into two groups with 100 series in each group. Ten reviewers - three musculoskeletal radiologists and seven orthopedic surgeons - performed radiograph analyses. These reviewers were randomly divided evenly into group one and group two. Reviewers were blinded to patient data and first reviewed 2V radiographs (AP/lateral) only, and then reviewed 4V radiographs, including AP/lateral, and two additional oblique views for the same patients at least four weeks later. Acute pathology identification and the need for further imaging was assessed for all reviewers, and clinical decision-making (operative vs nonoperative treatment, need for admission, need for additional imaging) was assessed only by the seven orthopaedic surgeon reviewers. RESULTS: Mean sensitivity for pathology identification was 79% with 2V and 81% with 4V (P =0.25). Intra-observer kappa value was 0.81 (range 0.54-1.00). Additional oblique radiographs led orthopaedic reviewers to change their treatment recommendations in 62/329 patients (18.84%) (P <0.001). Eight of 329 radiographic series were identified as "critical misses." (2.43%) (P =0.004), when pathology was reported as normal or reviewers recommended nonoperative treatment on 2V radiographs but changed their recommendation to operative management after the addition of oblique radiographs. The number needed to treat (NNT) for any treatment change and for "critical misses" was 83 and 643, respectively. CONCLUSION: Although the addition of oblique radiographs may improve a clinician's ability to identify subtle pathologic findings not identified on 2V, it rarely leads to significant changes in treatment recommendations. Given the high NNT, limiting the usage of these oblique radiographs in the general patient population may reduce costs without significantly affecting patient care.

Radiation Dose during Transarterial Radioembolization: A Dosimetric Comparison of Cone-Beam CT and Angio-CT Technologies.

PURPOSE: To evaluate the radiation dose differences for intraprocedural computed tomography (CT) imaging between cone-beam CT and angio-CT acquired during transarterial radioembolization (TARE) therapies for hepatocellular carcinoma. MATERIALS AND METHODS: A retrospective cohort of 22 patients who underwent 23 TARE procedures were selected. Patients were imaged in both cone-beam CT and angio-CT rooms as a part of their conventional treatment plan. Effective dose contributions from individual CT acquisitions as well as the cumulative dose contributions from procedural 3D imaging were evaluated. Angiography dose contributions were omitted. Cone-beam CT images were acquired on a C-arm Philips Allura system. Effective doses were evaluated by coupling previously published conversion factors (effective dose per dose-area product) to patient's dose-area product meter readings after the procedure. Angio-CT images were acquired on a hybrid Canon Infinix-i Aquilion PRIME system. Effective doses from angio-CT scans were estimated using Radimetrics. Comparisons of a single patient's dose differential between the 2 technologies were made. RESULTS: The mean effective dose from a single CT scan was 6.42 mSv and 5.99 mSv in the cone-beam CT room and the angio-CT room, respectively (P = .3224), despite the greater field of view and average craniocaudal scan coverage in angio-CT. The mean effective dose summed across all CTs in a procedure was 12.89 mSv and 34.35 mSv in the cone-beam CT room and the angio-CT room, respectively (P = .0018). CONCLUSIONS: The mean effective dose per CT scan is comparable between cone-beam CT and angio-CT when considered in direct comparison for a single patient.

Optimizing Electronic Release of Imaging Results through an Online Patient Portal.

Purpose To determine an optimal embargo period preceding release of radiologic test results to an online patient portal. Materials and Methods This prospective discrete choice conjoint survey with modified orthogonal design was administered to patients by trained interviewers at four outpatient sites and two institutions from December 2016 to February 2018. Three preferences for receiving imaging results associated with a possible or known cancer diagnosis were evaluated: delay in receipt of results (1, 3, or 14 days), method of receipt (online portal, physician's office, or phone), and condition of receipt (before, at the same time as, or after health care provider). Preferences (hereafter, referred to as utilities) were derived from parameter estimates (ß) of multinomial regression stratified according to study participant and choice set. Results Among 464 screened participants, the response and completion rates were 90.5% (420 of 464) and 99.5% (418 of 420), respectively. Participants preferred faster receipt of results (P < .001) from their physician (P < .001) over the telephone (P < .001). Each day of delay decreased preference by 13 percentage points. Participants preferred immediate receipt of results through an online portal (utility, -.57) if made to wait more than 6 days to get results in the office and more than 11 days to get results by telephone. Compared with receiving results in their physician's office on day 7 (utility, -.60), participants preferred immediate release through the online portal without physician involvement if followed by a telephone call within 6 days (utility, -0.49) or an office visit within 2 days (utility, -.53). Older participants preferred physician-directed communication (P < .001). Conclusion The optimal embargo period preceding release of results through an online portal depends on the timing of traditional telephone- and office-based styles of communication. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Arenson et al in this issue.

Novel EPHB4 Receptor Tyrosine Kinase Mutations and Kinomic Pathway Analysis in Lung Cancer.

Lung cancer outcomes remain poor despite the identification of several potential therapeutic targets. The EPHB4 receptor tyrosine kinase (RTK) has recently emerged as an oncogenic factor in many cancers, including lung cancer. Mutations of EPHB4 in lung cancers have previously been identified, though their significance remains unknown. Here, we report the identification of novel EPHB4 mutations that lead to putative structural alterations as well as increased cellular proliferation and motility. We also conducted a bioinformatic analysis of these mutations to demonstrate that they are mutually exclusive from other common RTK variants in lung cancer, that they correspond to analogous sites of other RTKs' variations in cancers, and that they are predicted to be oncogenic based on biochemical, evolutionary, and domain-function constraints. Finally, we show that EPHB4 mutations can induce broad changes in the kinome signature of lung cancer cells. Taken together, these data illuminate the role of EPHB4 in lung cancer and further identify EPHB4 as a potentially important therapeutic target.

Alzheimer disease alters the relationship of cardiorespiratory fitness with brain activity during the stroop task.

BACKGROUND: Despite mounting evidence that physical activity has positive benefits for brain and cognitive health, there has been little characterization of the relationship between cardiorespiratory (CR) fitness and cognition-associated brain activity as measured by functional magnetic resonance imaging (fMRI). The lack of evidence is particularly glaring for diseases such as Alzheimer disease (AD) that degrade cognitive and functional performance. OBJECTIVE: The aim of this study was to describe the relationship between regional brain activity during cognitive tasks and CR fitness level in people with and without AD. DESIGN: A case-control, single-observation study design was used. METHODS: Thirty-four individuals (18 without dementia and 16 in the earliest stages of AD) completed maximal exercise testing and performed a Stroop task during fMRI. RESULTS: Cardiorespiratory fitness was inversely associated with anterior cingulate activity in the participants without dementia (r=-.48, P=.05) and unassociated with activation in those with AD (P>.7). Weak associations of CR fitness and middle frontal cortex were noted. LIMITATIONS: The wide age range and the use of a single task in fMRI rather than multiple tasks challenging different cognitive capacities were limitations of the study. CONCLUSIONS: The results offer further support of the relationship between CR fitness and regional brain activity. However, this relationship may be attenuated by disease. Future work in this area may provide clinicians and researchers with interpretable and dependable regional fMRI biomarker signatures responsive to exercise intervention. It also may shed light on mechanisms by which exercise can support cognitive function.