Citations

Abstract Erdheim-Chester disease (ECD) is a rare histiocytosis of the “L” (Langerhans) group with multisystem involvement that can affect the large and medium-sized arteries mimicking vasculitis. Aortic involvement is common but the frequency and outcome of aortic branch vessel abnormalities are less well described. Patients with ECD were retrospectively identified. Images containing information of arterial involvement within 6 months of diagnosis were considered baseline and compared to last follow-up studies. Two physicians independently reviewed the studies to evaluate for presence of abnormalities attributable to ECD. Age and sex-adjusted logistic regression models were used to examine associations between patient characteristics and vessel involvement at baseline. Among a cohort of 64 patients with ECD, 63 had baseline imaging of vascular structures. ECD involvement of at least 1 segment of the aorta was observed in 56%. Abnormalities were also observed in aortic arch branches (26%), visceral branch arteries (40%), iliofemoral arteries (31%), coronary (5%), and pulmonary (3%) arteries. Perinephric fibrosis was strongly associated with the identification of abnormalities in the thoracic aorta (OR 4.92 [1.54, 15.75]; P = .007), abdominal aorta (OR 7.57 [2.28, 25.07]; P = .001) and visceral branch arteries (OR 6.05 [1.52, 24.03]; P = .01) but not pelvic/lower extremity arteries. Complete normalization of arterial abnormalities at follow-up was only observed in 9% or less of arterial segments involved at baseline. Aortic and aortic branch vessel abnormalities are frequently observed in patients with ECD and are often asymptomatic. Partial and/or complete resolution of arterial findings is uncommon.

ObjectiveTo identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment.MethodsThis retrospective case–control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross‐sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3‐variable) using the C‐reactive protein level (DAS28‐CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends.ResultsOverall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28‐CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease‐modifying medication use was not different between cases and controls.ConclusionThe findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.

202 Background: Fractional CO2 laser therapy is an emerging treatment for GSM. The objective of this study was to determine the feasibility, tolerability and preliminary efficacy of fractional CO2 laser therapy in BC survivors. Methods: This was a single arm feasibility study of BC survivors with dyspareunia and/or vaginal dryness. Participants received three treatments with office-based fractional CO2 laser on at least 30 day intervals and returned for a one-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in a minimum of 80% of patients. Primary efficacy was evaluated using the mean change (∆) in the score on the Vaginal Assessment Scale (VAS). Secondary efficacy endpoints included mean ∆ in scores on the Female Sexual Function Index (FSFI) and Urogenital Distress Inventory (UDI). Descriptive statistics (means and 95% confidence intervals (CI) for continuous variables and proportions for categorical variables) were used. Results: The study is ongoing with 65 patients enrolled. To date, 37 patients have completed all study treatments and follow-up. Median age for those who have completed treatment was 57 years (range 34-72). Most were ER/PR positive (78%) and Her 2 negative (81%) with stage I (43%) or II (41%) BC. Ninety-five percent were receiving endocrine therapy, most commonly aromatase inhibitors (73%). No SAEs were reported in the 37 patients who have completed study treatments and their outcomes are as follows. Based on the VAS, 78% reported moderate-severe dyspareunia and 89% reported moderate-severe vaginal dryness at baseline. At follow up, 28% reported moderate-severe dyspareunia and 28% reported moderate-severe vaginal dryness. The VAS score improved from baseline to follow up (mean ∆ 4.1; 95% CI [3.1, 5.1]). Similarly, the FSFI score improved (mean ∆ -10.0; 95% CI [-13.2, -6.9]) and the UDI score improved (mean ∆ -5.7; 95% CI [-10.1, -1.3]). Final efficacy analysis will be reported once all patients have completed all time points. Conclusions: Fractional CO2 laser treatment is feasible and tolerable in BC survivors and may reduce symptom burden from GSM. A randomized controlled trial with sham laser is currently in development. Clinical trial information: NCT03307044.

Abstract Chimeric antigen receptor T (CAR-T) cell therapy is a new pillar in cancer therapeutics; however, its application is limited by the associated toxicities. These include cytokine release syndrome (CRS) and neurotoxicity. Although the IL-6R antagonist tocilizumab is approved for treatment of CRS, there is no approved treatment of neurotoxicity associated with CD19-targeted CAR-T (CART19) cell therapy. Recent data suggest that monocytes and macrophages contribute to the development of CRS and neurotoxicity after CAR-T cell therapy. Therefore, we investigated neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potential strategy to manage CART19 cell–associated toxicities. In this study, we show that GM-CSF neutralization with lenzilumab does not inhibit CART19 cell function in vitro or in vivo. Moreover, CART19 cell proliferation was enhanced and durable control of leukemic disease was maintained better in patient-derived xenografts after GM-CSF neutralization with lenzilumab. In a patient acute lymphoblastic leukemia xenograft model of CRS and neuroinflammation (NI), GM-CSF neutralization resulted in a reduction of myeloid and T cell infiltration in the central nervous system and a significant reduction in NI and prevention of CRS. Finally, we generated GM-CSF–deficient CART19 cells through CRISPR/Cas9 disruption of GM-CSF during CAR-T cell manufacturing. These GM-CSFk/o CAR-T cells maintained normal functions and had enhanced antitumor activity in vivo, as well as improved overall survival, compared with CART19 cells. Together, these studies illuminate a novel approach to abrogate NI and CRS through GM-CSF neutralization, which may potentially enhance CAR-T cell function. Phase 2 studies with lenzilumab in combination with CART19 cell therapy are planned.

Objectives The aim of this study was to evaluate if a high-resolution photon-counting detector computed tomography (PCD-CT) system with a 1024×1024 matrix reconstruction can improve the visualization of fine structures in the lungs compared with conventional high-resolution CT (HRCT). Materials and Methods Twenty-two adult patients referred for clinical chest HRCT (mean CTDI vol, 13.58 mGy) underwent additional dose-matched PCD-CT (mean volume CT dose index, 13.37 mGy) after written informed consent. Computed tomography images were reconstructed at a slice thickness of 1.5 mm and an image increment of 1 mm with our routine HRCT reconstruction kernels (B46 and Bv49) at 512 and 1024 matrix sizes for conventional energy-integrating detector (EID) CT scans. For PCD-CT, routine B46 kernel and an additional sharp kernel (Q65, unavailable for EID) images were reconstructed at 1024 matrix size. Two thoracic radiologists compared images from EID and PCD-CT noting the highest level bronchus clearly identified in each lobe of the right lung, and rating bronchial wall conspicuity of third- and fourth-order bronchi. Lung nodules were also compared with the B46/EID/512 images using a 5-point Likert scale. Statistical analysis was performed using a Wilcoxon signed rank test with a P < 0.05 considered significant. Results Compared with B46/EID/512, readers detected higher-order bronchi using B46/PCD/1024 and Q65/PCD/1024 images for every lung lobe (P < 0.0015), but in only the right middle lobe for B46/EID/1024 (P = 0.007). Readers were able to better identify bronchial walls of the third- and fourth-order bronchi better using the Q65/PCD/1024 images (mean Likert scores of 1.1 and 1.5), which was significantly higher compared with B46/EID/1024 or B46/PCD/1024 images (mean difference, 0.8; P < 0.0001). The Q65/PCD/1024 images had a mean nodule score of 1 ± 1.3 for reader 1, and −0.1 (0.9) for reader 2, with one reader having improved nodule evaluation scores for both PCD kernels (P < 0.001), and the other reader not identifying any increased advantage over B46/EID/1024 (P = 1.0). Conclusions High-resolution lung PCD-CT with 1024 image matrix reconstruction increased radiologists' ability to visualize higher-order bronchi and bronchial walls without compromising nodule evaluation compared with current chest CT, creating an opportunity for radiologists to better evaluate airway pathology.

Purpose: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. Methods: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. Results: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. Conclusion: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.