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Introduction Patients with germline variants in CDH1 who undergo prophylactic total gastrectomy (TG) are at risk of altered nutrient and drug absorption due to modified gastrointestinal anatomy. Bone mineral density loss and micronutrient deficiencies have not been described previously in this patient population. Methods In this study we included 94 patients with germline CDH1 variants who underwent prophylactic TG between October 2017 and February 2022. We examined pre- and post-gastrectomy bone mineral density (BMD); serum biomarkers including calcium, phosphorus, alkaline phosphatase, and 25 (OH)-vitamin D; and postoperative adherence to calcium and multivitamin supplementation. Results Almost all patients (92/94, 98%) lost a substantial amount of weight post-TG, with an average weight loss of 26.5% at 12 months post-surgery. Serum biomarkers of mineral metabolism, namely calcium and phosphorus, did not change significantly after TG. However, average BMD was decreased in all patients at 12 months post-TG. Nonadherence to calcium supplementation was associated with a decrease in BMD. Nonadherence to multivitamin supplementation was associated with greater percent BMD loss in the femoral neck and total hip. Conclusions Appropriate micronutrient supplementation and nutritional counseling pre- and postoperatively in patients undergoing prophylactic TG are important to mitigate the long-term effects of gastrectomy on bone health.

Chimeric antigen receptor (CAR) T cells effectively eradicate medullary B-cell acute lymphoblastic leukemia (B-ALL) and can traffic to and clear central nervous system (CNS) involvement. CAR T-cell activity in non-CNS extramedullary disease (EMD) has not been well characterized. We systematically evaluated CAR T-cell kinetics, associated toxicities, and efficacy in B-ALL non-CNS EMD. We conducted a retrospective review of B-ALL patients with non-CNS EMD who were screened for/enrolled on one of three CAR trials (CD19, CD22, and CD19/22) at our institution. Non-CNS EMD was identified according to histology or radiographic imaging at extramedullary sites excluding the cerebrospinal fluid and CNS parenchyma. Of ∼180 patients with relapsed/refractory B-ALL screened across multiple early-phase trials over an 8-year period, 38 (21.1%) presented with isolated non-CNS EMD (n = 5) or combined medullary/non-CNS EMD (n = 33) on 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging. A subset receiving CAR T cells (18 infusions) obtained FDG PET/CT scans preinfusion and postinfusion to monitor response. At best response, 72.2% (13 of 18) of patients showed a medullary minimal residual disease–negative complete remission and complete (n = 7) or partial (n = 6) non-CNS EMD response. Non-CNS EMD responses to CAR T cells were delayed (n = 3), and residual non-CNS EMD was substantial; rarely, discrepant outcomes (marrow response without EMD response) were observed (n = 2). Unique CAR-associated toxicities at non-CNS EMD sites were seen in select patients. CAR T cells are active in B-ALL non-CNS EMD. Still, non-CNS EMD response to CAR T cells may be delayed and suboptimal, particularly with multifocal disease. Serial FDG PET/CT scans are necessary for identifying and monitoring non-CNS EMD.

© Published by Oxford University Press on behalf of the British Society for Rheumatology 2022. This work is written by US Government employees and is in the public domain in the US., Objectives: To assess whether data from 18F-fluorodeoxyglucose (FDG) PET should be incorporated into eligibility criteria for clinical trials in Takayasu's arteritis (TAK). Methods: The study was conducted in two parts. Part one was an international online survey among physicians with experience managing TAK to determine, using clinical vignettes, whether FDG-PET data influence decisions about enrolment in trials. Part two used patient data from an observational cohort study in TAK to assess agreement regarding decisions about enrolment into trials, based on clinical assessment with and without incorporation of FDG-PET data. Results: In part one, 68 physicians responded to the survey. Most physicians had used FDG-PET to diagnose TAK (82%) or monitor disease activity (66%). In vignettes representing active clinical disease, FDG-PET findings increased physician confidence in disease assessment and reduced outlier assessments. The greatest variability in decisions regarding enrolment into trials was observed in vignettes representing constitutional symptoms alone and elevated acute-phase reactants. In these cases, FDG-PET findings influenced decisions about enrolment and improved physician confidence. In multivariable models, FDG-PET findings were 1.29 times more strongly associated with enrolment decisions compared with levels of acute-phase reactants. In part two, incorporation of FDG-PET data significantly improved agreement about enrolment decisions between raters [inter-rater reliability (IRR) = 0.68 (95% CI 0.67, 0.69) to IRR = 0.88 (95% CI 0.87, 0.89); P < 0.01]. Conclusions: Incorporation of FDG-PET data into assessment of TAK influences decisions about enrolment of patients into trials, improves physician confidence about clinical assessment and could help reduce variability in study populations. Future trials in TAK should consider incorporating FDG-PET data into eligibility criteria.

Context Mutations in type I collagen or collagen-related proteins cause osteogenesis imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced mobility or intrinsic defects in osteoblast differentiation increasing adipocyte development. Objective This study compares adiposity and resting energy expenditure (REE) in OI and healthy controls (HC), for OI genotype- and Type-associated differences. Methods We studied 90 participants, 30 with OI (11 COL1A1 Gly, 8 COL1A2 Gly, 4 COL1A1 non-Gly, 1 COL1A2 non-Gly, 6 non-COL; 8 Type III, 16 Type IV, 4 Type VI, 1 Type VII, 1 Type XIV) and 60 HC with sociodemographic characteristics/BMI/BMIz similar to the OI group. Participants underwent dual-energy x-ray absorptiometry to determine lean mass and fat mass percentage (FM%) and REE. FM% and REE were compared, adjusting for covariates, to examine the relationship of OI genotypes and phenotypic Types. Results FM% did not differ significantly in all patients with OI vs HC (OI: 36.6% ± 1.9%; HC: 32.7% ± 1.2%; P = 0.088). FM% was, however, greater than HC for those with non-COL variants (P = 0.016). FM% did not differ from HC among OI Types (P values > 0.05). Overall, covariate-adjusted REE did not differ significantly between OI and HC (OI: 1376.5 ± 44.7 kcal/d; HC: 1377.0 ± 96 kcal/d; P = 0.345). However, those with non-COL variants (P = 0.016) and Type VI OI (P = 0.04) had significantly lower REE than HC. Conclusion Overall, patients with OI did not significantly differ in either extra-marrow adiposity or REE from BMI-similar HC. However, reduced REE among those with non-COL variants may contribute to greater adiposity.

The study rationale was to assess the performance of qualitative and semi-quantitative scoring methods for 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) assessment in large-vessel vasculitis (LVV). Methods: Patients with giant cell arteritis (GCA) or Takayasu's arteritis (TAK) underwent clinical and imaging assessment, blinded to each other, within a prospective observational cohort. FDG-PET-CT scans were interpreted for active vasculitis by central reader assessment. Arterial FDG uptake was scored by qualitative visual assessment using the PET vascular activity score (PETVAS) and by semi-quantitative assessment using standardized uptake values (SUV) and target-to-background ratios (TBR) relative to liver/blood activity. Performance of each scoring method was assessed by intra-rater reliability using the intra-class coefficient (ICC) and area under receiver-operator characteristic curves (AUC), using physician assessment of clinical disease activity and reader interpretation of vascular PET activity as independent reference standards. Wilcoxon signed-rank test was used to analyze change in arterial FDG uptake over time. Results: Ninety-five patients (GCA=52; TAK=43) contributed 212 FDG-PET studies. The ICC for semi-quantitative evaluation [0.99 (range 0.98-1.00)] was greater than the ICC for qualitative evaluation [0.82 (range 0.56-0.93)]. PETVAS and TBR metrics were more strongly associated with reader interpretation of PET activity than SUV metrics. All assessment methods were significantly associated with physician assessment of clinical disease activity, but the semi-quantitative metric TBRLiver¬ achieved the highest AUC (0.66). Significant but weak correlations with C-reactive protein were observed for SUV metrics (r = 0.19, p

To assess whether vascular activity seen onPatients with LVV were recruited into a prospective cohort. All patients underwent magnetic resonance angiography or computed tomography angiography and FDG-PET imaging. Follow-up imaging using the same imaging modalities was obtained ≥6 months later per a standardized imaging protocol. Arterial damage, defined as stenosis, occlusion, or aneurysm, and corresponding FDG uptake were evaluated in 17 arterial territories. On follow-up, development of new lesions was recorded, and existing lesions were characterized as improved, worsened, or unchanged.A total of 1,091 arterial territories from 70 patients with LVV (38 patients with Takayasu arteritis, 32 patients with giant cell arteritis) were evaluated. Over a median 1.6 years of follow-up, new lesions developed only in 8 arterial territories in 5 patients with Takayasu arteritis. Arterial lesions improved in 16 territories and worsened in 6 territories. Most arterial territories that did not have vascular activity on FDG-PET scan at baseline had no angiographic change over the follow-up period (787 [99%] of 793). Few territories with baseline FDG-PET activity had angiographic change over time (24 [8%] of 298), but of the territories that developed angiographic change, 80% had FDG-PET activity at baseline. Within the same patient, an arterial territory with baseline FDG-PET activity had significantly increased risk for angiographic change compared to a paired arterial territory without FDG-PET activity (odds ratio 19.49 [95% confidence interval 2.44-156.02]; P 0.01). Concomitant edema and wall thickening further increased risk for angiographic change.Development of angiographic change was infrequent in this cohort of patients with LVV. A lack of baseline FDG-PET activity was strongly associated with stable angiographic disease. In cases of angiographic progression, change was preceded by the presence of FDG-PET activity.

OBJECTIVE To assess the relationship between measures of disease assessment in patients with large vessel vasculitis. METHODS Patients with giant cell arteritis (GCA) or Takayasu arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: 1) patient-reported outcomes (Multidimensional Fatigue Inventory, patient global assessment of disease activity [PtGA], Short Form 36 health survey [SF-36], Brief Illness Perception Questionnaire), 2) physician global assessment of disease activity (PhGA), 3) laboratory outcomes (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR]), and 4) imaging outcomes (PETVAS, a qualitative score of vascular 18 F-fluorodeoxyglucose-positron emission tomography activity). RESULTS Analyses were performed on 112 patients (GCA = 56, TAK = 56), over 296 visits, with a median follow-up of 6 months. Correlation network analysis revealed assessment measures clustered independently by type of outcome. PhGA was centrally linked to all other outcome types, but correlations were modest (ρ = 0.12-0.32; P < 0.05). PETVAS, CRP level, and PtGA were independently associated with clinically active disease. All 4 patient-reported outcomes strongly correlated with each other (ρ = 0.35-0.60; P < 0.0001). Patient-reported outcomes were not correlated with PETVAS, and only PtGA correlated with CRP level (ρ = 0.16; P < 0.01). Patients whose clinical assessment changed from active disease to remission (n = 29) had a corresponding significant decrease in ESR, CRP level, and PETVAS at the remission visit. Patients whose clinical assessment changed from remission to active disease (n = 11) had a corresponding significant increase in CRP level and PtGA at the active visit. CONCLUSION Measures of disease assessment in large vessel vasculitis consist of independent, yet complementary, outcomes, supporting the need to develop composite outcome measures or a standard set of measures covering multiple types of outcomes.

OBJECTIVES: To determine the impact of imaging acquisition time on interpretation of disease activity on (18)F-fluorodeoxyglucose positron emission tomography (PET) in large-vessel vasculitis (LVV) and assess the relationship between clinical features and image acquisition time. METHODS: Patients with giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) were recruited into a prospective, observational cohort. After a single injection of FDG, all patients underwent two sequential PET scans at one and two-hour time points. Images were interpreted for active vasculitis by subjective assessment, qualitative assessment, and semi-quantitative assessment. Agreement was assessed by percent agreement, Cohen’s kappa, and McNemar’s test. Multivariable logistic regression identified associations between PET activity and clinical variables. RESULTS: 79 patients (GCA=44, TAK=35) contributed 168 paired one and two-hour PET studies. A total of 94 out of 168 scans (56%) were interpreted as active at the one-hour time point, and 129 scans (77%) were interpreted as active at the two-hour time point (p

Key Points Reexpansion of CAR T cells led to further investigations which confirmed the clonal nature of this expansion.

OBJECTIVE: Calcification of the coronary arteries, aorta, and branch vessels can occur in both large-vessel vasculitis (LVV) and atherosclerosis. The study objective was to determine the location and amount of vascular calcification in patients with LVV versus hyperlipidemia (HLD) and to identify risk factors associated with vascular calcification in LVV. METHODS: Patients with giant cell arteritis (GCA), Takayasu’s arteritis (TAK), and HLD underwent non-contrast computed tomography of the aorta and branch vessels. Vascular calcification in 14 specific arterial territories (4 segments of the aorta, 9 branch arteries, and the coronary arteries) was quantified throughout the large arteries by a cumulative Agatston score. Multivariate linear regression analyses were used to identify associations between traditional and disease-specific risk factors and total Agatston score. RESULTS: A total of 88 subjects, including GCA (n=29); TAK (n=22); and HLD (n=37), participated.Prevalence of vascular calcification in the aorta and branch vessels significantly differed in the coronary arteries (HLD=67%, GCA=35%, TAK=9%, p

The study rationale was to assess the performance of qualitative and semiquantitative scoring methods for (18)F-FDG PET assessment in large-vessel vasculitis. Methods: Patients with giant cell arteritis or Takayasu arteritis underwent independent clinical and imaging assessments within a prospective observational cohort. (18)F-FDG PET/CT scans were interpreted for active vasculitis by central reader assessment. Arterial (18)F-FDG uptake was scored by qualitative visual assessment using the PET vascular activity score (PETVAS) and by semiquantitative assessment using SUVs and target-to-background ratios (TBRs) relative to liver or blood activity. The performance of each scoring method was assessed by intrarater reliability using the intraclass correlation coefficient (ICC) and areas under the receiver-operating-characteristic curve, applying physician assessment of clinical disease activity and reader interpretation of vascular PET activity as independent reference standards. The Wilcoxon signed-rank test was used to analyze change in arterial (18)F-FDG uptake over time. Results: Ninety-five patients (giant cell arteritis, 52; Takayasu arteritis, 43) contributed 212 (18)F-FDG PET studies. The ICC for semiquantitative evaluation (0.99 [range, 0.98–1.00]) was greater than the ICC for qualitative evaluation (0.82 [range, 0.56–0.93]). PETVAS and target-to-background ratio metrics were more strongly associated with reader interpretation of PET activity than SUV metrics. All assessment methods were significantly associated with physician assessment of clinical disease activity, but the semiquantitative metric liver tissue-to-background ratio (TBR(Liver)) achieved the highest area under the receiver-operating-characteristic curve (0.66). Significant but weak correlations with C-reactive protein were observed for SUV metrics (r = 0.19, P < 0.01) and TBR(Liver) (r = 0.20, P < 0.01) but not for PETVAS. In response to increased treatment in 56 patients, arterial (18)F-FDG uptake was significantly reduced when measured by semiquantitative (TBR(Liver), 1.31–1.23; 6.1% change; P < 0.0001) or qualitative (PETVAS, 22–18; P < 0.0001) methods. Semiquantitative metrics provided information complementary to qualitative evaluation in cases of severe vascular inflammation. Conclusion: Both qualitative and semiquantitative methods of measuring arterial (18)F-FDG uptake are useful in assessing and monitoring vascular inflammation in large-vessel vasculitis. Compared with qualitative metrics, semiquantitative methods have superior reliability and better discriminate treatment response in cases of severe inflammation.

PURPOSE: To assess differences in FDG-PET/CT uptake among four subtypes of renal tumors: clear cell RCC (ccRCC), papillary type I and II RCC (pRCC), and oncocytoma. METHODS: This retrospective study investigated 33 patients with 98 hereditary renal tumors. Lesions greater than 1 cm and patients with a timeframe of less than 18 months between preoperative imaging and surgery were considered. FDG-PET/CT images were independently reviewed by two nuclear medicine physicians, blinded to clinical information. Volumetric lesion SUV(mean) was measured and used to calculate a target-to-background ratio respective to liver (TBR). The Shrout-Fleiss intra-class correlation coefficient was used to assess reliability between readers. A linear mixed effects model, accounting for within-patient correlations, was used to compare TBR values of primary renal lesions with and without distant metastasis. RESULTS: The time interval between imaging and surgery for all tumors had a median of 77 (Mean: 139; Range: 1–512) days. Intra-class reliability of mean TBR resulted in a mean κ score of 0.93, indicating strong agreement between the readers. The mixed model showed a significant difference in mean TBR among the subtypes (p < 0.0001). Pairwise comparison showed significant differences between pRCC type II and ccRCC (p < 0.0001), pRCC type II and pRCC type I (p = 0.0001), and pRCC type II and oncocytoma (p = 0.0016). Furthermore, a significant difference in FDG uptake was present between primary pRCC type II renal lesions with and without distant metastasis (p = 0.023). CONCLUSION: pRCC type II lesions demonstrated significantly higher FDG activity than ccRCC, pRCC type I, or oncocytoma. These findings indicate that FDG may prove useful in studying the metabolic activity of renal neoplasms, identifying lesions of highest clinical concern, and ultimately optimizing active surveillance, and personalizing management plans.

Context Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome (CS) associated mostly with Carney complex (CNC), a rare autosomal dominant multiple neoplasia syndrome. More than two-thirds of familial cases and approximately one-third of sporadic cases of CNC harbor germline inactivating PRKAR1A defects. Increasingly sensitive technologies for the detection of genetic defects such as next-generation sequencing (NGS) have further highlighted the importance of mosaicism in human disease. Case Description A 33-year-old woman was diagnosed with ACTH-independent CS with abdominal computed tomography showing bilateral micronodular adrenal hyperplasia with a left adrenal adenoma. She underwent left adrenalectomy with pathology demonstrating PPNAD with a 1.5-cm pigmented adenoma. DNA analysis by Sanger sequencing revealed 2 different PRKAR1A variants in the adenoma that were absent from DNA extracted from blood and saliva: c.682C > T and c.974-2A > G. “Deep” NGS revealed that 0.31% of DNA copies extracted from blood and saliva did in fact carry the c.682C > T variant, suggesting low-level mosaicism for this defect. Conclusions We present a case of PPNAD due to low-level mosaicism for a PRKAR1A defect which led to the formation of an adenoma due to a second, adrenal-specific, somatic PRKAR1A mutation. The identification of mosaicism for PRKAR1A, depending on the number and distribution of cells affected has implications for genetic counseling and tumor surveillance. This is the first recorded case of a patient with PRKAR1A mosaicism, PPNAD, and an adenoma forming due to complete inactivation of PRKAR1A in adrenal tissue from a second, somatic-only, PRKAR1A coding sequence mutation.

Objectives To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA. Methods Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints. Results Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3–27.0) vs 18.5 (IQR 15.3–23.8); P Conclusion Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.

Purpose: Simultaneously targeting the tumor and tumor microenvironment may hold promise in treating children with refractory solid tumors. Pexidartinib, an oral inhibitor of tyrosine kinases including colony stimulating factor 1 receptor (CSF-1R), KIT, and FLT3, is FDA approved in adults with tenosynovial giant cell tumor. A phase I trial was conducted in pediatric and young adult patients with refractory leukemias or solid tumors including neurofibromatosis type 1–related plexiform neurofibromas. Patients and Methods: A rolling six design with dose levels (DL) of 400 mg/m2, 600 mg/m2, and 800 mg/m2 once daily for 28-day cycles (C) was used. Response was assessed at regular intervals. Pharmacokinetics and population pharmacokinetics were analyzed during C1. Results: Twelve patients (4 per DL, 9 evaluable) enrolled on the dose-escalation phase and 4 patients enrolled in the expansion cohort: median (lower, upper quartile) age 16 (14, 16.5) years. No dose-limiting toxicities were observed. Pharmacokinetics appeared linear over three DLs. Pharmacokinetic modeling and simulation determined a weight-based recommended phase II dose (RP2D). Two patients had stable disease and 1 patient with peritoneal mesothelioma (C49+) had a sustained partial response (67% RECIST reduction). Pharmacodynamic markers included a rise in plasma macrophage CSF (MCSF) levels and a decrease in absolute monocyte count. Conclusions: Pexidartinib in pediatric patients was well tolerated at all DL tested, achieved target inhibition, and resulted in a weight-based RPD2 dose.

Objective Pseudostenosis is a magnetic resonance angiography (MRA) artifact that mimics arterial stenosis. The study objective was to compare imaging and clinical aspects of stenosis and pseudostenosis in a cohort of large‐vessel vasculitis (LVV), including giant‐cell arteritis (GCA) and Takayasu's arteritis (TAK). Methods Patients with LVV and comparator conditions (healthy or vasculopathies) underwent MRA of the aortic arch vessels. The subclavian and axillary arteries were systematically assessed for presence of stenosis and pseudostenosis by two independent readers. Serial and delayed imaging and clinical assessments were used to confirm suspected pseudostenoses. Multivariable regression analyses were used to identify associations between angiographic pathology and clinical findings. Results One hundred eighty‐four MRA scans were analyzed from patients with GCA (n = 36), TAK (n = 47), and comparators (n = 25). Pseudostenoses were frequently observed (48 of 184 scans, 26%) in the distal subclavian artery only on the side of injection and were shorter in length compared with true stenoses (25 mm vs 78 mm, P < 0.01). There was no difference in prevalence of pseudostenosis by diagnosis (GCA = 33%, TAK = 23%, comparator = 20%, P = 0.44), disease activity status (P = 0.31), or treatment status (P = 1.00). Percent and length of true stenosis were independently associated with pulse and blood pressure abnormalities in the upper extremity. Adjusting for length and stenosis degree, absence of collateral arteries was associated with arm claudication (odds ratio = 2.37, P = 0.03). Conclusion Although a pseudostenosis could be falsely interpreted as an arterial stenosis, radiographic and associated clinical features can help distinguish true disease from arterial susceptibility artifacts. In addition, the peripheral vascular examination can help to confirm a suspected true stenosis, as specific aspects of angiographic pathology are associated with vascular examination abnormalities in LVV.

Clinical use of cardiac cine CT imaging is limited by high radiation dose and low temporal resolution. To evaluate a low radiation dose, high temporal resolution cardiac cine CT protocol in human cardiac CT and phantom scans. CT scans of a circulating iodine target were reconstructed using the conventional single heartbeat half-scan (HS, approx. 175 ms temporal resolution) and the 3-heartbeat multi-segment (MS, approx. 58 ms) algorithms. Motion artifacts were quantified by the root-mean-square error (RMSE). Low-dose cardiac cine CT scans were performed in 55 subjects at a tube potential of 80 kVp and current of 80 mA. Image quality of HS and MS scans was assessed by blinded reader quality assessment, left ventricular (LV) free wall motion, and LV ejection rate. Motion artifacts in phantom scans were higher in HS than in MS reconstructions (RSME 188 and 117 HU, respectively; p = 0.001). Median radiation dose in human scans was 1.2 mSv. LV late diastolic filling was observed more frequently in MS than in HS images (42 vs. 26 subjects, respectively; p

ObjectivesTo assess agreement between interpretation of magnetic resonance angiography (MRA) and 18F-fluorodeoxyglucose positron emission tomography (PET) for disease extent and disease activity in large-vessel vasculitis (LVV) and determine associations between imaging and clinical assessments.MethodsPatients with giant cell arteritis (GCA), Takayasu’s arteritis (TAK) and comparators were recruited into a prospective, observational cohort. Imaging and clinical assessments were performed concurrently, blinded to each other. Agreement was assessed by per cent agreement, Cohen’s kappa and McNemar’s test. Multivariable logistic regression identified MRA features associated with PET scan activity.ResultsEighty-four patients (GCA=35; TAK=30; comparator=19) contributed 133 paired studies. Agreement for disease extent between MRA and PET was 580 out of 966 (60%) arterial territories with Cohen’s kappa=0.22. Of 386 territories with disagreement, MRA demonstrated disease in more territories than PET (304vs82, pConclusionsIn assessment of LVV, MRA and PET contribute unique and complementary information. MRA better captures disease extent, and PET scan is better suited to assess vascular activity. Clinical and imaging-based assessments often do not correlate over the disease course in LVV.Trial registration numberNCT02257866.

Objectives To assess the clinical value of 18F-flurodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large-vessel vasculitis (LVV) and disease comparators. Methods Patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA) were studied, along with a comparator group consisting of patients with hyperlipidemia, diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at six-month intervals. Performance characteristics of FDG-PET interpretation to differentiate clinically active LVV from disease comparators and from clinical remission were calculated. A qualitative summary score (PETVAS) based on global arterial FDG uptake was used to study associations between PET activity and clinical characteristics and to predict future relapse. Results 170 FDG-PET scans were performed in 115 participants (LVV=56; comparators=59). FDG-PET differentiated patients with clinically active LVV and disease comparators with a sensitivity=85% (95%CI: 69-94%) and specificity=83% (95%CI: 71-91%). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71, 58%). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with PET scan activity. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high versus low PETVAS (45% versus 11%, p=0.03) over a median follow-up of 15 months. Conclusions FDG-PET provides information about vascular inflammation that is complimentary to, and unique from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse. This article is protected by copyright. All rights reserved.

Objectives We sought to examine the relationship between visceral adipose tissue (VAT) and vascular inflammation (VI) by 18 fluorodeoxyglucose ( 18 FDG) positron-emission tomography (PET)/computed tomography (CT) in psoriasis (PSO). Furthermore, we evaluated whether treatment of PSO modulated VAT and VI. Background PSO, a chronic inflammatory skin disease, is associated with VI by 18 FDG PET/CT and increased cardiometabolic risk including adipose tissue dysregulation. Recently, VI was associated with future cardiovascular events; however, the relationship of visceral and subcutaneous adiposity with VI in PSO has yet to be evaluated. Methods Consecutive PSO patients (N = 77) underwent 18 FDG PET/CT scans to measure VI and abdominal adiposity. A subset of PSO patients with severe skin disease was scanned at 1 year following PSO treatment (N = 13). Results The cohort was middle aged (51.8 ± 12.6 years), predominantly male (n = 44, 57%), had low cardiovascular risk by Framingham 10-year risk (median 4 years [interquartile range (IQR): 2 to 7 years]), and mild-to-moderate skin disease (5.2 [IQR: 3.0 to 8.5]). PSO disease severity associated with VAT (β = 0.33; p = 0.004) beyond SAT (β = 0.30; p = 0.005). VAT (β = 0.55; p Conclusions Volume-based CT measurement of VAT may capture metabolic risk associated with VI compared to subcutaneous adipose tissue in PSO. PSO treatment associated with a decrease in VAT as well as decrease in VI suggesting VAT as a relevant biomarker related to VI in PSO.

Background: Follicular lymphoma (FL) shows marked variation in clinical course including spontaneous regression and histologic transformation (HT). Watchful waiting (W&W) is routinely applied to pts with newly diagnosed FL, but monitoring strategies are not standardized. Pts with progression within 1-2y of diagnosis have worse outcomes, but the biologic basis is unclear and biologic-based classifiers are not routinely applied at diagnosis. Circulating tumor DNA (ctDNA) is a highly tumor-specific biomarker that is prognostic in aggressive B-cell lymphomas, but its ability to serially monitor FL remains undefined. We applied a next-generation sequencing assay to identify tumor clonotypes for serial monitoring of peripheral blood in pts with untreated FL as part of an ongoing prospective clinical trial [NCT03190928]. Methods: Pts with grade I-II or 3A FL are eligible if evaluable disease on CT or FDG-PET, age ≥18, ECOG ≤2, no evidence of HT, and no prior systemic therapy. Pts undergo W&W until they meet uniform protocol-defined treatment criteria and remain on study until second-line therapy. Baseline testing includes labs, peripheral blood flow cytometry, BM biopsy/aspirate, CT and FDG-PET scans, and research biopsy. Pt have clinic visits every 4m for 2y, every 6m in years 3-5, then annually. CT scans are every 8m for 2y, then annually. FDG-PET scans are at baseline, at 2y, and any time of suspected progression. Peripheral blood samples including Streck tubes (plasma) and PBMCs are drawn at each clinic visit and stored. For ctDNA analysis, tumor DNA was amplified from FFPE using locus-specific primer sets for the Ig heavy-chain and light-chain loci along with BCL1/BCL2 translocations (Adaptive Biotechnologies). Amplified products were sequenced and tumor clonotypes were identified in plasma and PBMCs. Serial tracking of ctDNA was done in plasma and blinded to clinical outcomes. Results: 77 pts enrolled between July 2017 and July 2021. Median age was 57 (range 24-83) including 14 (18%) low-risk, 29 (38%) intermediate-risk, and 34 (44%) high-risk by FLIPI. Fourteen (18%) pts had stage I-II disease. Forty-three (56%) pts had monoclonal B-cells on peripheral blood flow cytometry. Twenty-nine (38%) pts progressed requiring frontline therapy including 7 (9%) pts with HT. Twenty-five (32%) pts were monitored ≥2y with no progression including 10 (13%) pts with evidence of at least some spontaneous regression by CT. Twenty (26%) pts were on study for Conclusions: ctDNA quantified from plasma in FL mirrors TMTV. Serial monitoring of ctDNA in patients without therapy demonstrated various patterns of fluctuation, including some patients in which ctDNA became undetectable coincident with spontaneous clinical regressions. ctDNA thus provides a non-invasive platform to monitor the natural history of FL, enabling future studies of tumor immune surveillance in this disease. Figure 1 Figure 1. Disclosures Jacob: Adaptive Biotechnologies: Current Employment, Current equity holder in publicly-traded company. Bagaev: BostonGene Corp.: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties: BostonGene. Meerson: BostonGene: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties: BostonGene. Postovalova: BostonGene Corp.: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties: BostonGene. Kudryashova: BostonGene: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties: BostonGene. Kotlov: BostonGene Corp: Current Employment, Current holder of stock options in a privately-held company, Patents & Royalties. Fowler: BostonGene: Current Employment, Current holder of stock options in a privately-held company.

Inflammation is a critical factor in early atherosclerosis and its progression to myocardial infarction. The search for valid surrogate markers of arterial vascular inflammation led to the increasing use of positron emission tomography/computed tomography. Indeed, vascular inflammation is associated with future risk for myocardial infarction and can be modulated with short-term therapies, such as statins, that mitigate cardiovascular risk. However, to better understand vascular inflammation and its mechanisms, a panel was recently convened of world experts in immunology, human translational research, and positron emission tomographic vascular imaging. This contemporary review first strives to understand the diverse roles of immune cells implicated in atherogenesis. Next, the authors describe human chronic inflammatory disease models that can help elucidate the pathophysiology of vascular inflammation. Finally, the authors review positron emission tomography–based imaging techniques to characterize the vessel wall in vivo.

Purpose To determine reader and computed tomography (CT) scan variability for measurement of coronary plaque volume. Materials and Methods This HIPAA-compliant study followed Standards for Reporting of Diagnostic Accuracy guidelines. Baseline coronary CT angiography was performed in 40 prospectively enrolled subjects (mean age, 67 years ± 6 [standard deviation]) with asymptomatic hyperlipidemia by using a 320-detector row scanner (Aquilion One Vision; Toshiba, Otawara, Japan). Twenty of these subjects underwent coronary CT angiography repeated on a separate day with the same CT scanner (Toshiba, group 1); 20 subjects underwent repeat CT performed with a different CT scanner (Somatom Force; Siemens, Forchheim, Germany [group 2]). Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were used to assess interreader, intrareader, and interstudy reproducibility. Results Baseline and repeat coronary CT angiography scans were acquired within 19 days ± 6. Interreader and intrareader agreement rates were high for total, calcified, and noncalcified plaques for both CT scanners (all ICCs ≥ 0.96) without bias. Scanner variability was ±18.4% (coefficient of variation) with same-vendor follow-up. However, scanner variability increased to ±29.9% with different-vendor follow-up. The sample size to detect a 5% change in noncalcified plaque volume with 90% power and an α error of .05 was 286 subjects for same-CT scanner follow-up and 753 subjects with different-vendor follow-up. Conclusion State-of-the-art coronary CT angiography with same-vendor follow-up has good scan-rescan reproducibility, suggesting a role of coronary CT angiography in monitoring coronary artery plaque response to therapy. Differences between coronary CT angiography vendors resulted in lower scan-rescan reproducibility.

LMB-100 is an immunotoxin targeting the cell surface protein mesothelin, which is highly expressed in many cancers including mesothelioma. Having observed that patients receiving pembrolizumab off protocol after LMB-100 treatment had increased tumor responses; we characterized these responses and developed animal models to study whether LMB-100 made tumors more responsive to antibodies blocking programmed cell death protein 1 (PD-1). The overall objective tumor response in the 10 patients who received PD-1 inhibitor (pembrolizumab, 9; nivolumab, 1) after progression on LMB-100 was 40%, and the median overall survival was 11.9 months. Of the seven evaluable patients, four had objective tumor responses, including one complete response and three partial responses, and the overall survival for these patients was 39.0+, 27.7, 32.6+, and 13.8 months. When stratified with regard to programmed death ligand 1 (PD-L1) expression, four of five patients with tumor PD-L1 expression had objective tumor response. Patients with positive tumor PD-L1 expression also had increased progression-free survival (11.3 versus 2.1 months, P = 0.0018) compared with those lacking PD-L1 expression. There was no statistically significant difference in overall survival (27.7 versus 6.8 months, P = 0.1). LMB-100 caused a systemic inflammatory response and recruitment of CD8(+) T cells in patients’ tumors. The enhanced antitumor effects with LMB-100 plus anti–PD-1 antibody were also observed in a human peripheral blood mononuclear cell–engrafted mesothelioma mouse model and a human mesothelin–expressing syngeneic lung adenocarcinoma mouse model. LMB-100 plus pembrolizumab is now being evaluated in a prospective clinical trial for patients with mesothelioma.

Background and aims Vitamin D exists as an inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream, which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)2D) in target tissues. Cohort studies reporting cardiovascular disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. Psoriasis, a chronic inflammatory disease, is a vitamin D deficient state and is associated with increased cardiovascular disease risk. While serum 25(OH)D is routinely measured, we hypothesized that measurement of 1,25(OH)2D in psoriasis may perform better than 25(OH)D in capturing cardiovascular risk. Methods Consecutive psoriasis patients (N = 122) at baseline underwent FDG PET/CT and CCTA scans to measure visceral adipose volume, aortic vascular uptake of FDG, and coronary plaque burden respectively. Blood levels of both 1,25(OH)2D and 25(OH)D were measured by chemiluminescence (LIAISON XL DIaSorin, Stillwater, MN). Results The psoriasis cohort was middle-aged (mean ± SD: 49.6 ± 13.0), predominantly male (n = 71, 58%), in majority Caucasians (n = 98, 80%), and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med. (IQR): 5.5 (3.2–10.7)], with almost one-fourth of the cohort on biologic psoriasis therapy for skin disease management (n = 32, 27%) at baseline. Interestingly, serum levels of 1,25(OH)2D but not 25(OH)D were found to be inversely associated with visceral adipose, a marker of cardiometabolic risk in fully adjusted models (β = − 0.43, p = 0.026 and β = −0.26 p = 0.13). Similarly, we found an inverse relationship between 1,25(OH)2D, but not 25(OH)D, and aortic vascular uptake of FDG independent of traditional risk factors (β = −0.19, p = 0.01). Finally, we found that serum 1,25(OH)2D, but not 25(OH)D, was inversely associated with non-calcified coronary plaque burden, as measured by CCTA independent of traditional risk factors (β = −0.18, p = 0.03). Conclusions In conclusion, we demonstrate that low 1,25(OH)2D levels were associated with visceral adipose volume, vascular uptake of FDG and coronary plaque burden independent of traditional risk factors, suggesting that 1,25(OH)2D may better capture the cardiometabolic risk associated with vitamin D deficient states.

ObjectiveTo compare the presence of head, neck and upper extremity symptoms in patients with Takayasu’s (TAK) and giant cell arteritis (GCA) and their association with vascular inflammation assessed by18F-fluorodeoxyglucose positron emission tomography (FDG-PET) or arterial damage assessed by magnetic resonance angiography (MRA).MethodsPatients with TAK and GCA underwent clinical and imaging assessments within 24 hours, blinded to each other. Vascular inflammation was defined as arterial FDG-PET uptake greater than liver by visual assessment. Arterial damage was defined as stenosis, occlusion, or aneurysm by MRA. Clinically reported symptoms were compared with corresponding imaging findings using generalised mixed model regression. Cranial symptoms were studied in association with burden of arterial disease in the neck using ordinal regression.ResultsParticipants with TAK (n=56) and GCA (n=54) contributed data from 270 visits. Carotidynia was reported only in patients with TAK (21%) and was associated with vascular inflammation (pConclusionThe distribution of symptoms and association with imaging abnormalities differs in patients with TAK and GCA. These findings may help clinicians predict associated FDG-PET and MRA findings based on a specific clinical symptom.Clinical trial registration numberNCT02257866.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) can detect vascular inflammation in large-vessel vasculitis (LVV). Clinical factors that influence distribution of FDG into the arterial wall and other tissues have not been characterized in LVV. Understanding these factors will inform analytic strategies to quantify vascular PET activity. Patients with LVV (n = 69) underwent 141 paired FDG-PET imaging studies at one and two hours per a delayed image acquisition protocol. Arterial uptake was quantified as standardized uptake values (SUVMax). SUVMean values were obtained for background tissues (blood pool, liver, spleen). Target-to-background ratios (TBRs) were calculated for each background tissue. Mixed model multivariable linear regression was used to identify time-dependent associations between FDG uptake and selected clinical features. Clinical factors associated with FDG distribution differed in a tissue- and time-dependent manner. Age, body mass index, and C-reactive protein were significantly associated with arterial FDG uptake at both time points. Clearance factors (e.g. glomerular filtration rate) were significantly associated with FDG uptake in background tissues at one hour but were weakly or not associated at two hours. TBRs using liver or blood pool at two hours were most strongly associated with vasculitis-related factors. These findings inform standardization of FDG-PET protocols and analytic approaches in LVV.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Neuroendocrine tumors occur in approximately in 5–15% of MEN1 patients. Very few cases of ovarian NETs have been reported in association with clinical MEN1 and without genetic testing confirmation. Thirty-three-year-old woman with MEN1 was found to have right adnexal mass on computed tomography (CT). Attempt at laparoscopic removal was unsuccessful, and mass was removed via a minilaparotomy in piecemeal fashion. Pathology showed ovarian NET arising from a teratoma. Four years later, patient presented with recurrence involving the pelvis and anterior abdominal wall. She was treated with debulking surgery and somatostatin analogs (SSAs). Targeted DNA sequencing analysis on the primary adnexal mass as well as the recurrent abdominal wall tumor confirmed loss of heterozygosity (LOH) at the MEN1 gene locus. This case represents to our knowledge, the first genetically confirmed case of ovarian NET arising by a MEN1 mechanism in a patient with MEN1. Extreme caution should be exercised during surgery as failure to remove an ovarian NET en masse can result in peritoneal seeding and recurrence. For patients with advanced ovarian NETs, systemic therapy options include SSAs, peptide receptor radioligand therapy (PRRT) and novel agents targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF). Learning points: Ovarian NET can arise from a MEN1 mechanism, and any adnexal mass in a MEN1 patient can be considered as a possible malignant NET. Given the rarity of this disease, limited data are available on prognostication and treatment. Management strategies are extrapolated from evidence available in NETs from primaries of other origins. Care should be exercised to remove ovarian NETs en bloc as failure to do so may result in peritoneal seeding and recurrence. Treatment options for advanced disease include debulking surgery, SSAs, TKIs, mTOR inhibitors, PRRT and chemotherapy. Background Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition, caused by a germline mutation in the MEN1 gene, leading to the development of tumors of the parathyroid glands, anterior pituitary and enteropancreatic endocrine cells. NETs are well-differentiated neuroendocrine neoplasms originating from enterochromaffin cells typically disseminated throughout the gastrointestinal and bronchopulmonary system and can also occur in patients with MEN1 (1). NETs are traditionally classified based upon the embryologic site of origin (foregut, midgut or hindgut), morphologic pattern and silver stain affinity differences (insular, trabecular, mucinous, strumal or mixed). Newer classification systems have been developed to emphasize the considerable clinical and histopathologic variability of NETs found within each embryologic site of origin. The most recent WHO 2017 classification differentiates pancreatic NETs into three grades (low, intermediate and high), and other gastrointestinal NETs into two grades (low and intermediate) on the basis of mitotic count per high power field and proliferative index (Ki-67) (2). The majority of MEN1 syndrome-associated NETs are of foregut origin (thymus 24%, bronchus 27%, stomach 3% and duodenum 14%). Ovarian NETs are rare, comprising 0.1% of all ovarian neoplasms, and very few cases of primary ovarian NET in patients with MEN1 syndrome have been reported in the literature (1, 3). However, none of the cases reported confirmed the origin of tumor by a MEN1 mechanism (loss of heterozygosity at MEN1 locus) (1, 4). Given their rarity, data regarding treatment of ovarian NETs are limited. Here, we present a case of primary ovarian NET arising from a teratoma in a patient with MEN1 with targeted DNA sequencing of the tumor. A brief discussion about challenges and recent advances in the management of primary ovarian NETs follows.

BACKGROUND: The contribution of inflammation to the incidence of cardiovascular disease (CVD) has been increasingly recognized in recent years. We investigated the relationship of aortic vascular uptake of 18F-FDG by PET/CT and aortic wall thickness (AWT) by MRI in psoriasis, a chronic inflammatory disease with increased incidence of CVD.165 patients with plaque psoriasis participated in an ongoing longitudinal cohort study. Subclinical atherosclerosis was assessed as aortic uptake of 18F-FDG by PET/CT reported as target to background ratio (TBR) and AWT by MRI reported as maximal thickness. RESULTS: Patients with psoriasis were middle-aged, predominantly male and had mild CV risk by traditional risk factors. Psoriasis severity as measured by PASI score was a notable determinant of AWT (ρ=0.20, p=0.01). Moreover, aortic vascular uptake of 18F-FDG associated with AWT by MRI at baseline in unadjusted analysis (β=0.27 p=0.001) and following adjustment for traditional cardiovascular risk factors, waist-to-hip ratio and statin use (β=0.21 p=0.01). Finally, following one year of psoriasis treatment, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT in fully adjusted models (β=0.33, p=0.02). CONCLUSION: In conclusion, we demonstrate that psoriasis severity and aortic vascular uptake of 18F-FDG in the aorta were associated with AWT. Following treatment of psoriasis, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT at one-year. These findings suggest that aortic vascular uptake of 18F-FDG is associated with early evidence of vascular disease assessed by aortic wall thickness. Prospective studies in larger populations including other inflammatory diseases are warranted.

Introduction Neuroendocrine tumors (NETs) are neoplasms that can arise from the neuroendocrine cells distributed widely throughout the body. Majority of NETs overexpress somatostatin receptors (SSTR) on their cell surface. This biologic characteristic is exploited in the SSTR-based imaging such as 111In octreotide scintigraphy and 68Ga DOTATATE positron emission tomography (PET)/CT. These modalities are currently considered standard for initial evaluation of suspected NETs. Although highly sensitive and specific, recent reports demonstrate a concerning incidence of “false-positive” physiologic uptake of these tracers in the pancreatic head - a confounding common site of NET involvement. Case report: A 78 year-old woman presented to clinic with a year-long history of diarrhea. Serum vasoactive intestinal peptide (VIP) levels were slightly elevated at 134.2 pg/mL. CT showed a mildly enhancing 2.5x1.8x2.8 cm area in the pancreatic uncinate process which corresponded to moderate focal uptake with 68Ga DOTATATE PET/CT. A presumptive diagnosis of NET was made, and the patient was scheduled to undergo Whipple’s surgery. She sought a second opinion at our institution. A subsequent MRI showed no lesion in the uncinate process and the patient’s surgery was deferred. Thereafter, her VIP levels spontaneously normalized. Endoscopic ultrasound (EUS) with fine needle aspiration cytology of the uncinate process showed normal pancreatic acini with no evidence of NET. Conclusion Conspicuous physiological uptake has been reported in the pancreatic head on 16-70% of 68Ga DOTATATE or 68Ga DOTANOC PET/CT scans, and 26% of the 111In octreotide scintigraphy scans.1 Image-based quantitative attempts to distinguish physiologic from pathologic uptake using SUVmax have rendered mixed results. When evaluating SSTR-based imaging uptake in the pancreatic head, patients can benefit from a higher index of suspicion of false positive uptake. Such cases require additional confirmation by means such as MRI or EUS. The patient described above also had mild contrast enhancement on CT, but an MRI didn’t show any corresponding lesion. Because of potential morbidity and mortality related to false positive uptake, a systematic review with evidence-based recommendations for imaging may benefit patient care. 1. Brabander T, et al. Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide: Incidence and Mechanism. Clin Nucl Med 2017;42:15-9. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Background: Psoriasis, a chronic inflammatory disease, is associated with accelerated vascular inflammation (VI) by FDG PET/CT and increased cardiometabolic dysfunction, including adipose tissue dysregulation. Both visceral and subcutaneous adipose volume are associated with sub-clinical aortic VI as well as future cardiovascular events, however, the relationship of adipose inflammation (assessed as adipose FDG uptake) with sub-clinical aortic VI has never been characterized in psoriasis. Methods: 104 consecutive biologic naïve psoriasis patients underwent FDG PET/CT scans to measure VI and adipose FDG uptake, represented as target-to-background ratio (TBR) and standardized uptake value (SUV) respectively. After identification of anatomical location (vertebral level T10), a single 3D-volume region of interest with a fixed volume (4.0 cm 3 ) was placed in the subcutaneous adipose to measure FDG uptake as standardized uptake value (SUV) using a dedicated software (OsiriX MD, Geneva, Switzerland). Results: The cohort was middle-aged, predominantly male, low CV risk by Framingham risk score and mild-moderate psoriasis. Adipose FDG uptake significantly associated with skin disease severity as well as aortic VI even beyond traditional risk factors (β=0.33, p=0.001 and β=0.24, p=0.014 respectively). Additionally, adipose FDG uptake mediated the association between psoriasis skin disease severity and aortic VI accounting for 23% of the total effect (Figure). Conclusions: Our study demonstrated that adipose inflammation is positively associated with psoriasis severity as well as aortic VI. Moreover, adipose inflammation also mediated the relationship between skin disease severity and aortic VI, suggesting that it may contribute to the potential link between psoriasis and CV disease. However, larger studies are needed to confirm our findings.

Objective.Disease activity in large-vessel vasculitis (LVV) is traditionally assessed by clinical and serological variables rather than vascular imaging. This study determined the effect of treatment on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) vascular activity in relation to clinical- and serologic-based assessments.Methods.Patients with giant cell arteritis (GCA) or Takayasu arteritis (TA) were prospectively evaluated at 6-month intervals in an observational cohort. Treatment changes were made at least 3 months before the followup visit and categorized as increased, decreased, or unchanged. Imaging (FDG-PET qualitative analysis), clinical, and serologic (erythrocyte sedimentation rate, C-reactive protein) assessments were determined at each visit and compared over interval visits.Results.Serial assessments were performed in 52 patients with LVV (GCA = 31; TA = 21) over 156 visits. Increased, decreased, or unchanged therapy was recorded for 36-, 23-, and 32-visit intervals, respectively. When treatment was increased, there was significant reduction in disease activity by imaging, clinical, and inflammatory markers (p ≤ 0.01 for each). When treatment was unchanged, all 3 assessments of disease activity remained similarly unchanged over 6-month intervals. When treatment was reduced, PET activity significantly worsened (p = 0.02) but clinical and serologic activity did not significantly change. Treatment of GCA with tocilizumab and of TA with tumor necrosis factor inhibitors resulted in significant improvement in imaging and clinical assessments of disease activity, but only rarely did the assessments both become normal.Conclusion.In addition to clinical and serologic assessments, vascular imaging has potential to monitor disease activity in LVV and should be tested as an outcome measure in randomized clinical trials.