Paraneoplastic musculoskeletal disorders: review and update for radiologists.

Rheumatic paraneoplastic syndromes are rare syndromes that occur at distant sites from the underlying tumor and may involve the bones, joints, fasciae, muscles, or vessels. In the absence of a known tumor, early recognition of a rheumatic syndrome as paraneoplastic permits dedicated work-up for, and potentially early treatment of an occult malignancy. Although there is a continuously growing list of paraneoplastic rheumatic disorders, not all of these disorders have a well-established association with a neoplastic process. The goals of this article are to review the clinical characteristics, diagnostic work-up, and imaging findings of well-documented rheumatic paraneoplastic disorders.

Revisiting the Case of Sarah Newbury's Death from Mollities Ossium.

Multiple myeloma and its precursor and variant types represent some of the most common hematologic malignancies in adults. These plasma cell dyscrasias are well-known in modern medicine. There are well-established clinical, laboratory, and pathologic criteria for diagnosis and staging. There is debate about the diagnosis of some of the earliest cases of myeloma described in the literature. We present a critical review of one such case.

Myeloma Response Assessment and Diagnosis System (MY-RADS): strategies for practice implementation.

Structured reporting systems have been developed for many organ systems and disease processes beginning with BI-RADS in 1993. Numerous reports indicate that referring health care providers prefer structured reports. Reducing variability of reports from one radiologist to another helps referring physician and patient confidence. Changing radiologists practice habits from completely free text to structured reports can be met with some resistance, but most radiologists quickly find that structured reports make their job easier. Whole-body MR studies are recommended as first-line imaging, by the International Myeloma Working Group (IMWG), for all patients with suspected diagnosis of asymptomatic myeloma and/or initial diagnosis of solitary plasmacytoma. Whole-body MR imaging (WBMRI) has been shown to have equal or greater sensitivity and specificity compared to PET/CT for detection of bone marrow involvement. Changing to WBMRI from other imaging modalities can be difficult for referring providers. Patient acceptance is high. MY-RADS is for myeloma patients who have WBMRI studies done. The intent of the system is to promote uniformity in MR imaging acquisition, diagnostic criteria, and response assessment and to diminish differences in the subsequent interpretation and reporting. A secondary benefit is a report template that provides a guide for interpretation for radiologists who may not have previously dictated these difficult studies. The characterization of bone marrow abnormalities in myeloma patients usually is fairly straightforward. To date, there is no standardized scoring or risk stratification of abnormalities nor is there an imaging atlas of abnormalities.

Society of Skeletal Radiology- white paper. Guidelines for the diagnostic management of incidental solitary bone lesions on CT and MRI in adults: bone reporting and data system (Bone-RADS).

The purpose of this article is to present algorithms for the diagnostic management of solitary bone lesions incidentally encountered on computed tomography (CT) and magnetic resonance (MRI) in adults. Based on review of the current literature and expert opinion, the Practice Guidelines and Technical Standards Committee of the Society of Skeletal Radiology (SSR) proposes a bone reporting and data system (Bone-RADS) for incidentally encountered solitary bone lesions on CT and MRI with four possible diagnostic management recommendations (Bone-RADS1, leave alone; Bone-RADS2, perform different imaging modality; Bone-RADS3, perform follow-up imaging; Bone-RADS4, biopsy and/or oncologic referral). Two algorithms for CT based on lesion density (lucent or sclerotic/mixed) and two for MRI allow the user to arrive at a specific Bone-RADS management recommendation. Representative cases are provided to illustrate the usability of the algorithms.

Updates and Ongoing Challenges in Imaging of Multiple Myeloma: AJR Expert Panel Narrative Review.

Advances in the understanding and treatment of multiple myeloma have led to the need for more sensitive and accurate imaging of intramedullary and extramedullary disease. This role of imaging is underscored by recently revised imaging recommendations of the International Myeloma Working Group (IMWG). This narrative review discusses these recommendations from the IMWG for different disease stages, focusing on advanced whole-body modalities, and addresses related challenges and controversies. In the recommendations, whole-body low-dose CT is central in initial patient assessment, replacing the conventional skeletal survey. Although the recommendations favor MRI for diagnosis because of its superior sensitivity and utility in identifying myeloma-defining events, FDG PET/CT is recommended as the modality of choice for assessing treatment response. Consensus opinions are offered regarding the role of imaging in multiple myeloma for characterization of disease distribution, determination of prognosis, and response evaluation.

Incidental long bone cartilage lesions: is any further imaging workup needed?

OBJECTIVE: To determine the rate of chondrosarcoma in incidentally discovered painless long bone cartilage lesions and to determine if any further imaging is needed. MATERIALS AND METHODS: A cartilage lesion was said to be an enchondroma when it had characteristic matrix mineralization and no aggressive features. Search of all imaging reports and tumor board files for keywords enchondroma, cartilage lesion, chondroid, and chondrosarcoma. Retrospective review of medical records and imaging studies from 4.5-year period. Data points collected included patient age, sex, lesion site, size, symptoms, type of imaging, imaging appearance, and length of follow-up. Only patients with no pain were included as enchondroma. Patients with final diagnosis of chondrosarcoma were included for comparison of all features. RESULTS: Only 1/73 (1.4%) patients with an initial incidentally discovered painless lesion was later diagnosed, with new symptoms, as atypical cartilage tumor. Average age was 59.4 years. Bones involved were the femur (n = 33), humerus (n = 30), tibia (n = 7), fibula (n = 2), and ulna (n = 1). Average enchondroma size was 3.9 cm (range 1.4-11.5). Average follow-up was 47 months (range 2-196 months). Eleven long bone chondrosarcomas were identified. All chondrosarcoma patients had pain and aggressive imaging findings. CONCLUSION: Our study reveals that the rate of chondrosarcoma in incidentally found painless chondroid lesions without aggressive features in long bones is low. Imaging follow-up may be needed only in the setting of new symptoms.

Distribution of Femoral Metastases; Potential Role for Extended FDG PET/CT Scanning.

This study investigates the distribution of femoral metastases in cancer patients, specifically addressing the incidence of distal femoral metastases. PET/CT examinations routinely extend only to mid-thigh level, precluding detection of distal metastases. We found a total of 208 femoral metastases in 112 patients. 30% had distal femoral metastases in addition to other areas of involvement. 7% of patients with femoral metastases had only distal femur disease. 6 patients had distal pathologic fractures. Exclusion of the distal femur during PET/CT may result in a missed or delayed diagnosis that could contribute to the development of a pathologic fracture with increased morbidity.

Dual energy CT can aid in the emergent differentiation of acute traumatic and pathologic fractures of the pelvis and long bones.

PURPOSE: To determine whether dual energy CT (DECT) scanning can aid in the differentiation between acute traumatic and pathologic fractures of the pelvis and long bones. METHODS: Retrospective review of 11 patients with 15 pathologic fractures proven by biopsy and/or other advanced imaging modalities. Age- and sex-matched patients with non-pathologic traumatic fractures were used as controls. Studies were reviewed by two readers on syngo.via software before and after the creation of virtual bone marrow color maps. Hounsfield units (HU) of the marrow space at the level of the fracture were recorded on both reviews. Differences between the HU of the bone marrow of traumatic and pathologic fractures were compared using two-tailed unpaired t-test. RESULTS: A statistically significant difference was found in the HU of the affected bone marrow on DECT virtual noncalcium bone marrow color maps between the pathologic group (mean HU:4.89) and the non-pathologic group (mean HU: - 286.2) (p = 0.0177). HU measurements on the mixed kVp images were 150.4 for the pathologic and 94.1 for the non-pathologic fracture groups, respectively, with no statistical significance (p = 0.272). CONCLUSIONS: DECT scanning can aid in the differentiation between hematoma at acute traumatic fracture sites and neoplasm at pathologic fracture sites. HU of the bone marrow is higher for pathologic fractures, and the difference in bone marrow attenuation is more evident on the virtual bone marrow color maps.

Performance of the Asthma Impact on Quality of Life Scale (A-IQOLS) in diverse asthma research populations and demographic subgroups.

BACKGROUND: The Asthma Impact on Quality of Life Scale (A-IQOLS) assesses the patient-perceived negative effect of asthma on quality of life. Its standard error of measurement is known; it has strong construct, convergent, and divergent validity; and it provides information that is unique among asthma outcome measures. OBJECTIVE: We sought to characterize the psychometric properties of the A-IQOLS and its suitability for use in demographically and clinically diverse adult asthmatic populations. METHODS: Data from participants in 5 independent asthma studies, with samples ranging from patients with well-controlled moderate asthma to patients with severe poorly controlled asthma, were pooled to determine the psychometric performance of A-IQOLS scores overall and in multiple demographic, disease status, and study subgroups. RESULTS: Pooled sample (n = 597) age averaged 45 years; 66% were female, 65% were white, 22% were African American, 11% were Hispanic, and 11% had a high school education or less. The rated importance of its underlying life dimensions and associations between A-IQOLS scores and lung function, symptom, Asthma Control Test, Juniper Mini Asthma Quality of Life Questionnaire, and Marks Asthma Quality of Life Questionnaire scores was very similar, regardless of patients' demographic and clinical characteristics. A-IQOLS scores discriminated among the individual study samples, as well as other patient-reported symptom and functional status measures. Distribution and anchor-based considerations suggest an A-IQOLS minimum clinically important difference in the vicinity of 0.50 and not less than 0.33 scale score units. CONCLUSIONS: A-IQOLS is valid for research and potentially clinical use in demographically and clinically diverse patients.

Long term follow-up of neoadjuvant chemotherapy for non-small cell lung cancer (NSCLC) investigating early positron emission tomography (PET) scan as a predictor of outcome.

BACKGROUND: Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy. METHODS: In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion. RESULTS: Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85). CONCLUSIONS: This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy. TRIAL REGISTRATION: NCT00227539 registered September 28th, 2005.

Association of Patient Self-Reported Shoulder Scores to Quantitative and Semiquantitative MRI Measures of Rotator Cuff Intramuscular Fatty Infiltration: A Pilot Study.

OBJECTIVE. The purpose of this study was to determine the relationship of supraspinatus fat fraction and Goutallier grade to the American Shoulder and Elbow Surgeons (ASES) score in cohorts of older adults with painful full-thickness supraspinatus tendon (SST) tear and control subjects. SUBJECTS AND METHODS. Seventeen control subjects and 15 study participants with painful full-thickness SST tear were prospectively recruited (mean age ± SD, 63.0 ± 10.1 years and 62.6 ± 9.0 years, respectively). Study participants received shoulder MRI and completed ASES questionnaires at one time. Goutallier grade was assessed on T1-weighted MRI. Fat fraction was measured on 6-point Dixon MRI. Body mass index (BMI) was determined. Descriptive, correlation, reliability, and regression analyses were performed. RESULTS. The control and painful full-thickness SST tear cohorts differed in mean supraspinatus fat fraction (3.3% ± 1.4% and 7.3 ± 5.9%, respectively; p = 0.024) and Goutallier grade (0.4 ± 0.5 and 0.9 ± 0.7, respectively; p = 0.022). Fat fraction (p = 0.014) and Goutallier grade (p = 0.017) showed a significant inverse association with ASES score only in the SST tear cohort. The association of BMI to ASES score was significant only in the control group (p = 0.036). The correlation between BMI and fat fraction were different for the two groups (control cohort, r = 0.676 and p = 0.003; SST tear cohort, r = 0.124 and p = 0.687). Fat fraction showed strong interobserver reliability (intraclass correlation coefficient, 0.903); Goutallier grade showed poor interobserver reliability (κ = 0.178). CONCLUSION. The association of ASES score and supraspinatus fat fraction or Goutallier grade differs between patients with painful full-thickness SST tear and control subjects without symptoms. Although fat fraction shows strong reliability, Goutallier grade should be regarded cautiously because of suboptimal reproducibility. Our results also suggest that painful full-thickness SST tear alters the correlation between supraspinatus fat fraction and BMI as compared with control subjects.

A new measure to assess asthma's effect on quality of life from the patient's perspective.

BACKGROUND: The Asthma Impact on Quality of Life Scale (A-IQOLS) assesses the negative effect of asthma on quality of life (QoL) from the patient's perspective by using dimensions of Flanagan's Quality of Life Scale (QOLS), a measure of current QoL. OBJECTIVES: We sought to determine and compare the psychometric properties of the A-IQOLS and QOLS, including their sensitivities to differences and change in asthma status. METHODS: In a test-retest design (3- to 5-week interval) adults with persistent asthma underwent spirometry and were administered the A-IQOLS, other asthma outcome measures (Asthma Control Test, Asthma Symptom Utility Index, and the Marks and Juniper Asthma Quality of Life Questionnaires), and the QOLS. RESULTS: Participants' (n = 147) mean age was 49 years, 76% were white, 12% were Hispanic, and 65% were female. A-IQOLS and QOLS scores were significantly correlated with other asthma outcomes scores, except FEV1, but shared relatively low common variance with these measures. A-IQOLS but not QOLS score changes were significantly correlated with changes in asthma outcomes. An A-IQOLS standard error of measurement of 0.27 implies that a within-person score change of ±0.73 or greater constitutes a true change. The QOLS standard error of measurement was 0.43. CONCLUSIONS: A-IQOLS provides a reliable, valid, and unique assessment of the patient-perceived negative effect of asthma on QoL that is suitable for use in asthma clinical research and potentially in clinical care. Further studies are needed in diverse patient populations. QOLS, a measure of current QoL, is less sensitive to disease status changes but might be useful in characterizing study populations, in treatment adherence research, and as a clinical and research tool in patients with multiple, severe, and/or life-limiting chronic conditions.

Electromagnetic navigational bronchoscopic airway recanalization in patients with vanishing bronchus.

BACKGROUND: Stenosis is the most frequent airway complication after lung transplantation. When complete obstruction is diagnosed without possibility of recanalization, options are generally limited to either resection or retransplantation, both associated with increased morbidity and mortality. We describe our experience with a novel technique using electromagnetic navigational bronchoscopy (ENB) to recanalize the occluded airway after lung transplantation. METHODS: Patients who underwent lung transplantation between 2010 and 2016 with subsequent development of complete airway obstruction and failed conventional recanalization attempts were included in this study. All patients underwent attempted recanalization using ENB. Primary outcomes included success of the technique and long-term patency. Secondary outcomes included procedure-related complications. RESULTS: Four patients met inclusion criteria and underwent attempted recanalization using the ENB platform. Location of the obstruction was the bronchus intermedius in two patients, the lingular bronchus in one patient, and the left basilar bronchus in one patient. Mean length of stenosis was 8.8 mm. Three patients (75%) were successfully recanalized and all airways remain patent at 1, 48, and 66 mo. There were no procedure-related complications. The one patient who was unable to be recanalized successfully underwent bilobectomy and died 7 mo later. CONCLUSIONS: ENB is a feasible method of airway recanalization in select patients with bronchial occlusion after lung transplantation. ENB recanalization spares lung parenchyma and avoids risks associated with surgical resection and retransplantation. This novel technique can be added to the armamentarium for thoracic surgeons who diagnose and treat this complicated problem.

The Ability of Dual-Energy Computed Tomography to Distinguish Normal Bone Marrow From Metastases Using Bone Marrow Color Maps.

OBJECTIVE: The objective of this study was to determine if dual-energy computed-tomography bone marrow color maps can improve sensitivity, specificity, accuracy, and confidence of detection of bone metastases. METHODS: Institutional review board approved this retrospective review of a consecutive series of cancer patients. Two radiologists first evaluated the fused 120 kV computed tomography images and recorded a number of suspicious lesions, confidence level, and Hounsfield units for each lesion. After a time gap, the studies were randomized for a second review with dual-energy computed-tomography bone marrow color maps. RESULTS: Eighteen patients and 1105 bones were reviewed. A total of 227 true metastatic lesions were present. With bone marrow color map review, sensitivity increased from 76.2% to 86.8%, for reader 1, and from 80.2% to 92.8%, for reader 2. Specificity and accuracy also increased. Confidence level increased for 12 lesions. CONCLUSIONS: Dual-energy computed-tomography bone marrow color map analysis of patients with metastatic cancers can improve the sensitivity, specificity, accuracy, and confidence level for the detection of bone metastases.

Assessing the Benefits of Preoperative Thoracic Epidural Placement for Lung Transplantation.

OBJECTIVE: The authors investigated the effect of preoperative thoracic epidural (PreTE) catheter placement versus not placing a preoperative thoracic epidural catheter (NoPreTE) on the duration of postoperative ventilation time, time to become coherent (measured as time to become Confusion Assessment Method-intensive care unit [ICU] negative), opioid consumption, ICU length of stay (LOS), and hospital LOS. DESIGN: Retrospective cohort design. SETTING: Single institution, university hospital. PARTICIPANTS: Patients undergoing lung transplantation. COMPARISON GROUPS: PreTE group was defined as patients who received a thoracic epidural preoperatively. NoPreTE group was defined as patients who either received a thoracic epidural postoperatively or who did not receive a thoracic epidural postoperatively. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients for the PreTE and 99 for NoPreTE groups were included in the study. After a excluding patients with postoperative ventilation times greater than 96 hours, preoperative thoracic epidural was associated with shorter time on the ventilator (19.1 hours v 30.6 hours; p < 0.001), time to become coherent (26.4 hours v 37.6 hours; p = 0.008), ICU LOS (6.4 days v 12.4 days; p = 0.018), and hospital LOS (15.9 days v 23.5 days; p = 0.04) compared to patients who did not receive a preoperative epidural. After controlling for single versus double lung transplantation and duration of cardiopulmonary bypass (CPB), differences in time to become coherent, ICU LOS, and hospital LOS became nonsignificant. Opioid consumption was significantly higher in those patients who did not receive a preoperative epidural. Despite a high rate of anticoagulation for CPB (89.5%), no neurologic complications or epidural hematomas were observed. CONCLUSION: For those lung transplant patients ventilated for less than 96 hours postoperatively, preoperative thoracic epidural placement is associated with shorter postoperative ventilator time and reduced opioid consumption. Time to become coherent postoperatively, ICU LOS, and hospital LOS also improved in this cohort, though the significance decreased after adjusting for possible confounders. A larger prospective study is necessary to confirm if timing of thoracic epidural placement alters time to become coherent postoperatively and ICU LOS.

Multispectral Optical Tweezers for Biochemical Fingerprinting of CD9-Positive Exosome Subpopulations.

Extracellular vesicles (EVs), including exosomes, are circulating nanoscale particles heavily implicated in cell signaling and can be isolated in vast numbers from human biofluids. Study of their molecular profiling and materials properties is currently underway for purposes of describing a variety of biological functions and diseases. However, the large, and as yet largely unquantified, variety of EV subpopulations differing in composition, size, and likely function necessitates characterization schemes capable of measuring single vesicles. Here we describe the first application of multispectral optical tweezers (MS-OTs) to single vesicles for molecular fingerprinting of EV subpopulations. This versatile imaging platform allows for sensitive measurement of Raman chemical composition (e.g., variation in protein, lipid, cholesterol, nucleic acids), coupled with discrimination by fluorescence markers. For exosomes isolated by ultracentrifugation, we use MS-OTs to interrogate the CD9-positive subpopulations via antibody fluorescence labeling and Raman spectra measurement. We report that the CD9-positive exosome subset exhibits reduced component concentration per vesicle and reduced chemical heterogeneity compared to the total purified EV population. We observed that specific vesicle subpopulations are present across exosomes isolated from cell culture supernatant of several clonal varieties of mesenchymal stromal cells and also from plasma and ascites isolated from human ovarian cancer patients.

Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling.

Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high-resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue-simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor-kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue-related diseases.

Nonsupersymmetric Dualities from Mirror Symmetry.

We study supersymmetry breaking perturbations of the simplest dual pair of (2+1)-dimensional N=2 supersymmetric field theories-the free chiral multiplet and N=2 super QED with a single flavor. We find dual descriptions of a phase diagram containing four distinct massive phases. The equivalence of the intervening critical theories gives rise to several nonsupersymmetric avatars of mirror symmetry: we find dualities relating scalar QED to a free fermion and Wilson-Fisher theories to both scalar and fermionic QED. Thus, mirror symmetry can be viewed as the multicritical parent duality from which these nonsupersymmetric dualities directly descend.