bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-475 Thyroid Extranodal Diffuse Large B-Cell Lymphoma in Setting of Gastric Large B-Cell Lymphoma
Authors: Russell Yan , Schwartz Benjamin , Ventura Ana , Oprea Mihaela , Khokhar Jatinder , Guber Helena Abby 
Published: May 2020

Abstract
Background: We report a case of concomitant thyroid and gastric diffuse large B-cell lymphoma (DLBCL). Clinical Case: A 73 year-old man presented with melena of 2 days duration. EGD revealed a 1.5 x 0.7 cm gastric ulcer. Biopsy revealed marked chronic active gastritis with glandular atypia, positive for H. pylori. Repeat biopsy of the same ulcer post H. pylori treatment demonstrated high-grade B-cell lymphoma. Immunostains were positive for CD20, CD10, BCL6, cyclin D and negative for CD 23 and CD 30. More than 95% of tumor cells expressed Ki-67, while 10% expressed MUM-1 and BCL2. Benign T cells stained positive for CD3 and CD5. FISH was negative for gene rearrangement involving BCL-6/BCL-2 and C-MYC. Staging PET/CT showed hypermetabolic regions involving the stomach wall, large left neck mass and right lung focus. The neck focus had a max SUV 48.5 (8 fold greater than the other sites), that localized to a soft tissue mass measuring 4.9 x 2.7 cm. FNA of the left-sided thyroid mass showed diffuse large B-cell lymphoma with immunostain positive for CD20 and negative for cytokeratin AE1-3, PAX8, and CD 10. The morphology was similar to that of abnormal lymphoid cells in the gastric biopsy. Patient had normal thyroid function tests but positive autoimmune thyroid disease markers (TPO and anti-TG antibody). Treatment with R-CHOP resulted in shrinkage of neck mass. Conclusion: Hypermetabolic regions revealed by PET/CT at distant sites from primary tumor require further evaluation including biopsy as indicated. Clinical correlation and response to chemotherapy can provide supplemental information in the overall assessment of the disease process.
MON-196 A Single-Center Experience of Patients with Metastatic Pheochromocytoma/Paraganglioma Treated with 177Lu-DOTATATE
Authors: Roslyakova Anna , Beltsevich Dmitry , Plotkin Michail , Rumyantsev Pavel , Ladygina Daria 
Published: May 2020

Abstract
The prevalence of metastatic pheochromocytoma/paraganglioma (PPGL) is reported to be 3% to 36% of all the cases. The five-year overall survival rate of such patients ranges from 40 to 77%. The management of metastatic PPGL is challenging taking into account the fact that the optimal strategies for clinical care beyond surgical resection are not guided yet. Peptide receptor radionuclide therapy (PRRT) using somatostatin analogues is effective in other neuroendocrine tumours, can be indicated in patients with positive scans for the respective radiopharmaceuticals.
We report preliminary data of the prospective study aimed to assess the safety and efficacy outcomes of 177Lu-DOTATATE for 6 patients with histologically confirmed PPGLs with metastatic progression after the complete PPGL surgery. The mean age of our cohort was 53 years (range 14–73); an equal number of male and female patients was included. Two of them had germline mutations in RET and SDHB genes, respectively. Radiological response utilized RECIST 1.1 criteria; toxicity was graded according to common terminology criteria for adverse events version 4. PPRT scheme varied between three and four cycles. Partial response (PR) was achieved in one and stable disease (SD) in four 4 patients. One patient had treatment refractory with disease progression and dramatic increase of chromogranin A concentration (+268%). Biochemical response (&gt;50% decrease) of chromogranin A was found in 1/6 patients and of catecholamines in 2/6 patients. No hematological or kidney toxicity grade 3–4 was registered.
Median overall survival and median progression-free survival rate will be reported after the end of the study.
To date, about 250 PPGL patients have been treated with PRRT. PRRT using 177Lu-DOTA-SSAs has shown promise for treatment of PPGLs with improvement of clinical symptoms and/or disease control in the setting of retrospective small case reports or case series. However, more well-designed prospective studies are required to confirm these findings.
SUN-155 A Complex Case of Adrenal Insufficiency Associated with NLRP1 Gene Mutation in a Patient with Myopathy and Mitochondrial Cytopathy
Authors: Khan Mehvish , Khawaja Masuma , Haq Mohammad Adnan Ul , Quadir Humza , Jameson Brian C 
Published: May 2020

Abstract
Most cases of Addison’s disease are due to an autoimmune response, with the most commonly associated genes belonging to human leukocyte antigen (HLA) complex. Genome wide association studies have shown a significant association of variants of Nuclear Localization Leucine-Rich-Repeat Protein 1 (NLRP1) with Addison’s disease. NLRP1 protein is involved in the assembly of inflammasome which promotes the secretion of interleukin-1β, interleukin-18 and downstream inflammatory responses to regulate inflammation. With underlying myopathy and mitochondrial disease, coexisting adrenal insufficiency may be challenging to identify. A 36-year-old female presented for evaluation of fatigue, myalgia, and dyspnea for several years. She carried a diagnosis of asthma, myopathy, gastroparesis requiring a gastric stimulator, and recently diagnosed adrenal insufficiency secondary to long term fluticasone use. Beside low blood pressure of 91/64 millimetres of mercury, physical exam was unremarkable. Lab findings were significant for dehydroepiandrosterone-sulfate (DHEAS) of 7.0 micrograms per deciliter (mcg/dL), Adrenocorticotropic hormone (ACTH) of 7.2 picograms per milliliter and cortisol of 1.4 mcg/dL. Adrenal insufficiency was confirmed with cosyntropin stimulation test. Methacholine challenge test showed worsening asthma. She was managed with empiric stress dose steroids when indicated. Muscle fatigue progressed despite taking ubiquinol, B100 and carnitine. She was further evaluated with muscle biopsy that showed type two fiber atrophy. Muscle coenzyme Q10 was 0.08 mcg/dL, and citrate synthase was 50% of normal, insufficient for electron transport complex I. Whole exome sequencing showed mutations in NLRP1 in addition to Myosin Heavy Chain 2 (MYH2) and Sodium voltage-gated Channel alpha subunit 4 (SCN4a) both of which are associated with myopathy. She was then started on a short-acting glucocorticoid regimen. While her adrenal insufficiency was initially thought to be secondary to inhaled steroids, subsequent mutation analysis suggested that she was prone to autoimmunity. This case illustrates the association of adrenal insufficiency with NLRP1 mutation. Furthermore, the symptoms of adrenal insufficiency and myopathy can overlap making it difficult to delineate. While so far most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial deoxyribonucleic acid (DNA), a new field of investigation is that of syndromes due to mutations in the nuclear DNA.
SUN-586 CXCR2 Repression by Glucocorticoids in Adipose Tissue
Authors: Amatya Shripa , Carroll Natalie G , Petrillo Maria Grazia , Cidlowski John A , Topete Diana Cruz 
Published: May 2020

Abstract
Obesity-induced type 2 diabetes (T2D) is a significant risk factor of cardiovascular disease (CVD), which affects 28.1 million adults in the United States. Adipose tissue chronic inflammation is one of the main factors that drive obesity-induced insulin resistance (IR) and T2D. Despite several studies that have shown a link between obesity, adipose tissue inflammation, and IR/T2D, the mechanisms underlying this association are not well understood. Synthetic glucocorticoids are widely used for their potent anti-inflammatory actions; however, their use is hampered due to off-target side effects. Glucocorticoids exert profound effects on adipose tissue, including the regulation of adipocyte metabolism and immune functions. However, whether their effects on adipose tissue are positive or negative it is still a controversial topic. Genome-wide microarray data obtained from adipocyte-specific glucocorticoid receptor (GR) knockout (AdipoGRKO) mice showed that lack of GR leads to a significant increase in the expression of pro-inflammatory genes in white adipose tissue (WAT). Moreover, WAT isolated from adipoGRKO mice demonstrated significant increase in immune cell infiltration, which correlates with our gene expression data. Among the most up-regulated genes, we found the C-X-C Motif Chemokine Receptor 2 (CXCR2), which is a critical mediator of chemotaxis to the sites of inflammation. Although studies have shown the presence of CXCR2 in adipocytes and suggested the contribution of CXCR2 signaling in adipocyte development, its role in obesity-driven adipose tissue inflammation is unknown. This led us to hypothesize that adipocyte specific administration of glucocorticoids can reduce obesity-induced adipocyte inflammation by inhibiting CXCR2 gene transcription and signaling. Our in vitro studies using 3T3-L1 cells derived adipocytes showed that treatment with the synthetic glucocorticoid, Dexamethasone (Dex) led to a significant repression of CXCR2 mRNA and protein levels. Correlating with these results, Dex treatment significantly inhibited macrophage migration to adipocytes in a mechanism dependent on GR activation and repression of CXCR2. Furthermore, these results were recapitulated in vivo. Together our findings suggest that local delivery of glucocorticoids to adipose tissue could ameliorate inflammation and reduce the risk of developing IR and T2D.
OR03-03 New Insights into the Functional Human Adrenal Cortex Zonation
Authors: Camponova Paméla , Duparc Céline , Roy Malanie , Lefebvre Hervé , Thomas Michael 
Published: May 2020

Abstract
The zonation of the human adrenal cortex has long been established morphologically and histologically as three distinct layers of cells. The outer zona glomerulosa (ZG) comprises densely packed cells arranged in clusters that produce aldosterone; the zona fasciculata (ZF) is composed of cells with large cytoplasm, containing lipid droplets arranged in radial columns that synthetize cortisol; and the zona reticularis is composed of compact and pigmented cells producing androgens. The main purpose of this work was to study the expression of aldosterone synthase (CYP11B2 which catalyzes the last steps of aldosterone synthesis) and 11β-hydroxylase (CYP11B1 which catalyzes the last step of cortisol synthesis) in normal adrenal glands to address issues regarding the zonation and the fate of the cells constitutive of each zone through the expression of Ki-67 and cleaved Caspase-3. Thirty eight normal human adrenals (16 females, 22 males, ranging in age from 22 to 81 years old with a median age of 52 years old) were obtained from brain-dead organ donors (kindly provided by the Organ Transplant Clinics, University Hospital of Rouen). As early as 22 years old, we found that the histological ZG (h-ZG) does not correspond to the functional ZG (f-ZG) expressing CYP11B2. Moreover, the h-ZG CYP11B2- cells were CYP11B1+ showing that these cells ascribed to the h-ZG are in fact cortisol producing cells. The progressive replacement of CYP11B2+ cells by CYP11B1+ cells in the h-ZG might demonstrate the role of the extracellular matrix in the morphological maintenance of the adrenal cortex. Our analysis also showed that steroidogenic cells were either CYP11B1 or CYP11B2 positive. By immunofluorescence, we observed in many cases isolated or clusters of CYP11B2+ cells located deeply in the h-ZF and sometimes in the vicinity of the central vein. We were able to show that those cells were probably issued from CYP11B2+ cell clusters located in h-ZG which migrated centripetally. Ki-67 immunoreactivity was highly variable and observed throughout the entire cortex. We also found a positive correlation between the steroidogenic and endothelial cells proliferation. It is interesting to note that some Ki-67+ cells located in the h-ZG were CYP11B1+. Cortical cells positive for cleaved Caspase-3 were extremely rare but detected in all zones when present. These findings challenge the classic view of lineage conversion of differentiated ZG cells and show a new pathway where the CYP11B2+ cells migrate without changing their phenotype.
SUN-136 Clinico-Pathological Features, Treatment Modalities and Survival of Patients with Malignant Insulinoma: A Multicenter Study
Authors: Veltroni Alessio , Cosaro Elisa , Cingarlini Sara , Zatelli Maria Chiara , Maria Grossrubatscher Erika , Faggiano Antongiulio , Pia Anna Rosa , Bianchi Antonio , Piusceddu Sara , Spada Francesca , Piovesan Alessandro , Razzore Paola , Filice Angelina , Micciolo Rocco , Davi’ Maria Vittoria 
Published: May 2020

Abstract
Introduction: management of malignant insulinoma is challenging due to the need to control both hypoglycemic syndrome and tumor growth. Literature data is limited to small series.
Aim of the study: to analyze clinical-pathological characteristics, treatment modalities and prognosis of patients with malignant insulinoma.
Materials and methods: Multicenter retrospective study on 31 patients (M 61.3%) diagnosed between 1988 and 2017.
Results: The mean age at diagnosis was 48 ± 15 years. In 5 cases (16.1%) the hypoglycemic syndrome occurred after 46 ± 35 months from the diagnosis of NET, in 26 (83.9%) cases it led to the diagnosis of NET, of which 11 cases (42.3%) with mean diagnostic delay of 32.7 ± 39.8 months. The majority ​​of the NET were G2 (70.8 %) and in the pancreatic body-tail (78.6%). The mean NET diameter was 41 ± 31 mm. Metastases were widespread in 40.7%, only hepatic in 37%, only lymph nodal in 18.5%..Surgical treatment was performed in 21/31 (67.7%) with hypoglycemic control in 42.9%. Except for 2 patients with curative surgery, the others underwent further different lines of therapies including somatostatin analogues (SA), Peptide Receptor Radionuclide Therapy (PRRT), everolimus, chemotherapy, TAE/TACE/RFA, radiotherapy. PRRT was performed in 14/31 (45.1%) with complete (42.9 %) or partial (50%) syndrome control.
The median follow-up was 60 months. The 5-year survival rate was 62%. The median overall survival (OS) was 40 months. No significant difference in OS was observed according to the site of primary tumour and its dimension. A trend towards increased survival was found according to grading (5-year OS 100% for G1, 77% for G2, 33% for G3). Patients with Ki-67 ≤ 10% had a significant higher survival rate compared to patient with Ki-67 &gt;10% (5-year OS rate 87% vs 43%, p: 0.03). As regards the type of treatment, patients who underwent surgery had a higher survival rate than those who did not (5-year OS 76% vs 31.7%, p= 0.006). Moreover, patients receiving PRRT as II line treatment had a better prognosis than those who underwent it in further lines, although the 5-year OS was not significantly different (80% vs 25% respectively, p=0.057).
Conclusions: Our study includes the largest series of patients with malignant insulinomas up to now reported. The hypoglycemic syndrome may occur after years in initially non-functioning NETs, or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 &lt;10% are prognostic factors associated with better survival. PPRT seems to be promising in the control of hypoglycemic syndrome.
SUN-574 A1AT: Novel Inhibitor of Active PCSK9
Authors: Melendez Quantil , Wooten Catherine , Ahmed Sumaira , Williams Ariel Renee’ , Kimbro Kevin Sean , Lopez Dayami 
Published: May 2020

Abstract
Heart disease is the principal cause of death and disability for both men and women in the US, accounting for 40% of all annual deaths. African American populations are disproportionately burdened with metabolic diseases, due in part to cholesterol metabolism deficiencies. Elevated low density lipoprotein (LDL) cholesterol levels and inflammation promote atherogenic conditions which lead to heart disease. Proprotein convertase subtilisin/kexin-9 (PCSK9) is a biomarker which enhances athrogenic progression by controlling the number of LDL receptor molecules expressed at the plasma membrane. PCSK9 indirectly regulates LDL-cholesterol levels. Previous reports show some patients do not respond well to general anti-cholesterolemic treatments. We believe this is due to altered PCSK9 activity, which is currently not being evaluated. We have developed a novel assay to detect active PCSK9. A1AT is a SERPIN family member whose primary objective is inhibition of proteases. Specific levels of A1AT are required to maintain metabolic homeostasis. Based on this, we hypothesized that a specific ratio between A1AT serum levels and PCSK9 activity levels would eliminate statin intolerance/resistance, regulating LDL-cholesterol metabolism congruently. Using this novel active PCSK9 detection assay, we provide evidence that A1AT interacts with PCSK9 in the medium of C3A hepatic-like cells, preventing the formation of PCSK9/LDL receptor complexes in vitro. There was an approximate 20% inhibition in PCSK9-LDL receptor complex formation when liver cells were treated with recombinant A1AT (rA1AT). A dose dependent response analysis proved 200ng/ml of rA1AT had an 46% reduction in PCSK9 activity. We determined PCSK9 activty and A1AT levels correlate with key diabetic factors in humans, suggesting that A1AT could effect diabetes progression.
MON-063 Rare Cases of Local and Systemic Allergic Reactions Associated with Recombinant Human Growth Hormone Treatment Including Fixed Drug Eruption and Anaphylaxis
Authors: Kim Dae Hyun , Choi Ju-hee 
Published: May 2020

Abstract
Recombinant human growth hormone (rhGH) is widely used to increase growth velocity not only in growth hormone deficiency, but also in other growth related disorder to increase final adult height. RhGH is a safe and effective treatment, which has few side effects. Possible side effects include allergic reaction, joint pain, headache, progression of spine curvature in scoliosis, temporary increase in blood sugar levels. GH-associated allergic reactions include mostly local erythema and swelling at the injection site, and there have been a few reports about those reactions. However, we experienced fixed drug eruption associated with rhGH, which was thought to be an unusual local side effect. Also, we experienced another rare case showing GH-associated systemic allergic reactions including anaphylaxis, which have not been described. So, we would like to introduce these cases who developed repetitive allergic reactions to two different kinds of preservative-containing rhGH, fixed drug eruption and anaphylaxis. Case 1. At the time of initial visit, the patient was at the age of 9 years and 3 months with Tanner stage 3 development. Her height and weight was measured as 128cm (13%) and 27.6kg (24%). Bone age was advanced as 10.9 years by the TW3 method. She was diagnosed as precocious puberty, and combined treatment with GnRH analog and rhGH was started to delay rapid pubertal growth and improve her final adult height because of her short stature for advanced bone age. However, after 2 months of treatment, she showed oval shape of erythematous patch and urticaria on left cheek, which reappeared at the same site after switching to another kind of preservative-containing rhGH. The symptom was diagnosed as fixed drug eruption associated with rhGH therapy, and after discontinuing rhGH, the symptom resolved. Case 2. A 13 years and 8 months girl visited our clinic to check her growth status. She was 154.6cm (29%) tall and 40.1kg (9%), and showed Tanner stage IV development. Her MPH was calculated as 161.5cm, and pelvic AP x-ray showed Risser stage 3–4, which is compatible to 14.5–15 years of bone age in girls. Medical intervention for more height gain was thought to be ineffective, however, the patient and her parents strongly requested rhGH treatment. So, we decided to try rhGH treatment for only three months. However, after 1 weeks of treatment, she complaint of repetitive urticaria and itching sensation, which subsided after taking anti-histamine drugs. After switching to another kind of rhGH, she still complaint of generalized urticaria and itching sensation, aggravated with dyspnea and facing swelling especially around her eyes, the symptoms of anaphylaxis and angioedema. Because of those systemic allergic reactions from rhGH, we quit the treatment. In conclusion, physicians should be aware of these potential side effects and prepare appropriate management and evaluation of patients receiving rhGH treatment.
MON-710 ACVR1 Activation in Primary and iPS-Derived Human Skeletal Muscle Stem Cells Impairs Myogenic Transcriptional Signature and Function
Authors: Barruet Emilie , Garcia Steven , Tamaki Stanley , Morales Blanca M , Wu Jake , Moody Tania , Pomerantz Jason H , Hsiao Edward Chiaming 
Published: May 2020

Abstract
Developing optimal strategies for skeletal muscle regeneration and repair requires a detailed understanding of how these processes are regulated. The number of primary human satellite cells that can be obtained is usually extremely low, and may be impaired in disease of impaired skeletal muscle repair. One such condition is fibrodysplasia ossificans progressiva (FOP), a progressive disease characterized by massive heterotopic ossification in skeletal muscles and aberrant skeletal muscle repair after injury. FOP patients have activating mutations in the Activin A Type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. Our overall hypothesis is that activated ACVR1 signaling caused by the ACVR1 R206H mutation incites inappropriate activation of human muscle stem cells (satellite cells, PAX7 expressing cells), causing loss of muscle cell fate and aberrant muscle repair. Since human satellite cells are difficult to obtain from live tissue donors, and injury can trigger heterotopic ossification, we created human induced pluripotent stem cell (iPSC)-derived muscle stem cells (iMuSCs) from FOP and control iPSC lines. We found that control and FOP iPSCs can differentiate into PAX7+ cells with high efficiency. Control and FOP iMuSCs can regenerate injured mouse muscle and form new human fibers, but both showed few PAX7 cells after transplant. Single cell RNA sequencing showed cell heterogeneity, and specific subsets of PAX7+ cells. FOP iMuSCs showed a chondrogenic/osteogenic signature (e.g COL1A1, DCN, OGN) with higher p38 pathway signaling activity. Skeletal muscle samples from autopsies of patients with FOP also showed increased expression of COL1A1. Additionally, we found that primary human FOP satellite cells can engraft and regenerate injured muscle, but with lower efficiency than control satellite cells. These studies used a novel iMuSC strategy to elucidate how increased ACVR1 activity affects human satellite cells function, and compare these iMuSCs to primary human satellite cells. These approaches will be useful to identify new therapeutic targets for conditions affecting skeletal muscle, and will improve our understanding of how muscle and bone interact in development and disease pathophysiology.