tbuckley/cabot-search huggingface dataset:
THU0622 MRI OF THE CRANIO-CERVICAL JUNCTION IN RHEUMATOID ARTHRITIS – DEFINITION OF NORMAL AND PATHOLOGICAL FINDINGS
Authors: Katharina Ziegeler, Christoph Korsing, Mattias Bollow, Kay Geert A. Hermann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In rheumatoid arthritis (RA), disease involvement at the cervical spine is common and may lead to malposition of the dens axis, resulting in severe neurological impairment. To date, malalignment is mostly described by X-rays. <h3>Objectives</h3> The aim of this investigation was to systematically define osseous and ligamentous MRI-findings in cranio-cervical RA in comparison to a control group without the disease. <h3>Methods</h3> MRI datasets of patients with cranio-cervical RA were identified retrospectively from the institutional image database and matched regarding age and gender with control patients. All image datasets were systematically reviewed for: position and morphology of dens axis (including erosions and osteitis); width and angle of the cranio-cervical joints; length, angle and visibility of peridental ligaments; vascularization of peridental soft tissue. Prior to image analysis, an atlas of normal findings and measurements was comprised. Group differences were investigated using students T-test for continuous data and Fisher's exact test for nominal and ordinal data. <h3>Results</h3> A total of 40 patients were included in this retrospective case-control study, 20 in each group (RA and control). Position of dens was significantly more cranial in the RA group (dens to McGregor line: -1.62 mm for RA vs. 2.15 mm for controls, p=0.002; dens to McRae line: 3.20 for RA vs. 5.36 for controls, p&lt;0.001). Visibility of alar ligaments was significantly lower in RA patients (fully visible in 10% of RA and 35% of control patients, p=0.012). Similarly, signal of transverse ligaments was normal in 5% of RA vs. 35% of control patients (p&lt;0.001). There was no difference in length of the aforementioned ligaments (p≥0.056). <h3>Conclusion</h3> With this case control study, MRI data on the position of the osseous and ligamentous structures of the cranio-cervical junction in patients with rheumatoid arthritis are available for the first time. Cranialization of the dens axis and signal changes of the transverse ligament and the alar ligaments are the most obvious findings. In a next step, the diagnostic value of MRI of the cervical spine in RA should be prospectively investigated and the available scoring system developed into an internationally established outcome measure. <h3>Disclosure of Interests</h3> [2] Katharina Ziegeler: None declared, Christoph Korsing: None declared, Mattias Bollow: None declared, Kay Geert A. Hermann Speakers bureau: AbbVie, MSD, Pfizer, UCB, Samsung
Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data
Authors: Robert Haase, Peter Schlattmann, Pascal Gueret, Daniele Andreini, Gianluca Pontone, Hatem Alkadhi, Jörg Hausleiter, Mario J Garcia, Sebastian Leschka, Willem B Meijboom, Elke Zimmermann, Bernhard Gerber, U Joseph Schoepf, Abbas A Shabestari, Bjarne L Nørgaard, Matthijs F L Meijs, Akira Sato, Kristian A Ovrehus, Axel C P Diederichsen, Shona M M Jenkins, Juhani Knuuti, Ashraf Hamdan, Bjørn A Halvorsen, Vladimir Mendoza-Rodriguez, Carlos E Rochitte, Johannes Rixe, Yung Liang Wan, Christoph Langer, Nuno Bettencourt, Eugenio Martuscelli, Said Ghostine, Ronny R Buechel, Konstantin Nikolaou, Hans Mickley, Lin Yang, Zhaqoi Zhang, Marcus Y Chen, David A Halon, Matthias Rief, Kai Sun, Beatrice Hirt-Moch, Hiroyuki Niinuma, Roy P Marcus, Simone Muraglia, Réda Jakamy, Benjamin J Chow, Philipp A Kaufmann, Jean-Claude Tardif, Cesar Nomura, Klaus F Kofoed, Jean-Pierre Laissy, Armin Arbab-Zadeh, Kakuya Kitagawa, Roger Laham, Masahiro Jinzaki, John Hoe, Frank J Rybicki, Arthur Scholte, Narinder Paul, Swee Y Tan, Kunihiro Yoshioka, Robert Röhle, Georg M Schuetz, Sabine Schueler, Maria H Coenen, Viktoria Wieske, Stephan Achenbach, Matthew J Budoff, Michael Laule, David E Newby, Marc Dewey
Journal: BMJ (2019)

To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients.
Abstract 16722: L-2-Hydroxyglutarate Protects Against Myocardial Ischemia-Reperfusion Injury
Authors: Huamei HE, Ryan M Mulhern, Wusheng Xiao, William Oldham, Yi-Dong Lin, Ronglih Liao, Joseph Loscalzo
Journal: Circulation (2018)

Background: L-2-hydroxyglutarate (L2HG) couples mitochondrial (Mito) and cytoplasmic energy metabolism in a model of cellular redox regulation. Under conditions of limited oxygen availability, mammalian cells generate L2HG to counteract the adverse effects of Mito reductive stress induced by hypoxia. L2HG is oxidized to α-ketoglutarate by L2HG dehydrogenase (L2HGDH) in a variety of mammalian tissues, including the heart. Myocardial ischemia/reperfusion injury (MIRI) is a consequence of coronary vascular disease and vascular procedures. Mito oxidative stress plays a critical role in MIRI. Here we hypothesized that L2HG protects against MIRI. Methods and Results: We induced accumulation of L2HG by heterozygous (HET) and homozygous (KO) deletion of L2HGDH gene in mice. The hearts isolated from HET, KO, and wild-type (WT) littermate mice were subjected to 30 min global thermal ischemia followed by 60 min reperfusion. Cardiac function and energy metabolism were simultaneously measured using a Langendorff heart perfusion model and 31 P-NMR spectroscopy. We found that female HET and KO exhibited better recovery of cardiac function post-MIRI in consistent with better preservation of intracellular ATP and phosphocreatine (Table). Using HPLC, we measured compounds representative of cellular redox state (GSG, GSSG, NAD, NADH, NADP, NADPH, coenzyme A and ascorbate), cellular energy state (ATP, ADP, AMP, GTP, GDP, GMP, UTP, UDP, UMP, CTP, CDP, CMP, IMP, malonyl-CoA and acetyl-CoA), and nucleotide catabolism (adenosine, hypoxanthine, xanthine and inosine) in freeze-clamped hearts. We found that ratios of GSH/GSSG and ATP/ADP increased in HET and KO hearts (Table). Interestingly, the ratios of NADH/NAD and NADPH/NADP increased only in KO but not in HET hearts. Consistent with the increased ratio of ATP/AMP, hypoxanthine and xanthine decreased only in KO hearts but not in HET hearts (Table). Conclusion: The accumulation of L2HG in a genetic mouse model protects against MIRI though increasing cellular antioxidative capacity and preserving high energy phosphates. The underlying mechanism of these beneficial adaptive phenomena warrants further study. Targeting L2HG levels and L2HGDH expression may serve as new therapeutic strategies for MIRI protection.
A systems genomics approach identifies <i>SIGLEC15</i> as a susceptibility factor in recurrent vulvovaginal candidiasis
Authors: M. Jaeger, M. Pinelli, M. Borghi, C. Constantini, M. Dindo, L. van Emst, M. Puccetti, M. Pariano, I. Ricaño-Ponce, C. Büll, M. S. Gresnigt, X. Wang, J. Gutierrez Achury, C. W. M. Jacobs, N. Xu, M. Oosting, P. Arts, L. A. B. Joosten, F. L. van de Veerdonk, J. A. Veltman, J. ten Oever, B. J. Kullberg, M. Feng, G. J. Adema, C. Wijmenga, V. Kumar, J. Sobel, C. Gilissen, L. Romani, M. G. Netea
Journal: Science Translational Medicine (2019)

SIGLEC15 is a component of the host immune response against Candida albicans and is dysregulated in patients with recurrent vulvovaginal candidiasis.
PS1203 HEREDITARY SPHEROCYTOSIS: SCREENING AND DIAGNOSTIC APPROACH IN A BELGIAN LABORATORY
Authors: E. Sepulchre, A.-S. Adam, F. Cotton, E. Lazarova, B. Gulbis
Journal: HemaSphere (2019)

Background: As a reference center, we analyze erythrocyte membranes, enzymes, and hemoglobin for congenital hemolytic anemia (CHA) in cases that are not diagnosed using ordinary laboratory examinations, and we introduce genetic testing using a hemolytic anemia-related gene panel. We analyzed 136 cases from 2016 to 2017, including 36 patients under 1 year of age and 100 patients aged 1 year and over. Consequently, a definitive diagnosis was obtained for 84% of patients aged 1 and over but for only 72% of patients under 1 year of age. Aims: We aimed to summarize the final diagnosis for hemolytic anemia in patients less than 1 year of age analyzed over 3 years from 2016 to 2018 and discuss the common clinical features and laboratory data of undiagnosed cases. Methods: We analyzed 58 infantile CHA casesusing the following laboratory tests: flow-cytometric osmotic fragility (FCM-OF) test, eosin 5’-maleimide binding test, assay of 15 red blood cell (RBC) enzymes, reduced glutathione content, and isopropanol stability test for unstable hemoglobinopathy. For the cases with a difficult diagnosis, genetic analysis with target-captured sequencing (TCS) using a gene panel of 74 genes related to CHA was carried out. Results: Among 58 infants with CHA, we diagnosed 30 cases (52%); there were 18 cases of hereditary spherocytosis (HS), 2 cases of hereditary elliptocytosis (HE), 1 case of hereditary pyropoikilocytosis, 4 cases of erythro-enzymopathies, and 2 cases of unstable hemoglobinopathies. Among the 28 undiagnosed cases, 14 showed an elevated percentage of residual RBCs in the FCM-OF test. These cases also showed abnormal RBC morphologies such as target cells, stomatocytes, and/or pyknocytes. We performed TCS for 4 of the 14 cases, but none harbored mutations such as PIEZO1 or KCNN4. Of the 7 cases, which could be followed up to at the age of one year, all recovered from CHA within a year. Summary/Conclusion: Mild hemolytic anemia accompanied by stomatocytes and/or target cells is a typical clinical feature of dehydrated hereditary stomatocytosis (DHSt) in adults. We previously showed that FCM-OF clearly discriminated DHSt from HS or HE (Utsugisawa et al., Blood 2017;130:929). In this study, approximately half of the infants with undiagnosed CHA showed similar RBC morphology and higher osmotic resistance with no causative gene mutations. We noticed that clinical pictures of these infants resembled the description of infantile pyknocytosis (IP), which is a transient neonatal hemolytic anemia with the characteristic RBC morphology. As IP cases follow a relatively benign clinical course, we propose that FCM-OF may be used as a biomarker for the tentative diagnosis of IP.
FRI0615 EVALUATION OF COMPLIANCE AND RELATED FACTORS IN COLCHICINE TREATMENT IN FAMILIAL MEDITERRANEAN FEVER PATIENTS
Authors: Emre Tekgoz, Seda Colak, Fatma İlknur Cinar, Sedat Yilmaz, Muhammet Çınar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is an autoinflammatory disease requiring long-term treatment. Increasing the compatibility with colchicine treatment in patients with FMF is the first step for preventing amyloidosis. Patients' beliefs about medicines and treatment may affect treatment adherence and treatment success. <h3>Objectives</h3> The aim of this study was to determine adherence to colchicine treatment and related factors in FMF patients. In addition, patients' beliefs about colchicine, which are one of the important factors affecting the treatment adherence of patients, were evaluated. <h3>Methods</h3> Total of 179 patients with FMF was included in this study. The demographic and clinical features and MEFV gene mutations were recorded. The treatment adherence of the patients was assessed using by Compliance Questionnaire on Rheumatology (CQR). The Beliefs About Medicines Questionnaire (BMQ-T) was used to assess patient's beliefs about colchicine. The relationship between compliance of treatment and clinical characteristics of patients were assessed. <h3>Results</h3> One hundred thirteen (63.1%) of the patients were male. The mean age of patients was 34.5 ± 12.7 years and mean delay in diagnosis was 6.7 ± 8.4 years. The mean dose of colchicine was 1.37 ± 0.43 mg/day and, the percentage of patients using colchicine regularly was 66.5%. Adherence to treatment was higher in patients with concomitant diseases than those without comorbidities (p = 0.028). In addition, treatment compliance was higher in married patients compared to single patients (p = 0.013). The colchicine dose used in compatible patients was higher than in non-compatible patients (p = 0.033) (Table 1). We also found that as the BMQ-T Specific Necessity scores increased, compliance with treatment increased. On the other hand, as the BMQ-T General Overuse and General Harm scores increased, non-compliance with treatment increased (Table 2). <h3>Conclusion</h3> In patients with FMF, it is important to evaluate the compliance with the treatment due to the importance of colchicine to prevent amyloidosis that may occur in patients without treatment. As this study shows it is also important to determine patients' beliefs about medicine in terms of their influence on patients' compliance with treatment. <h3>Disclosure of Interests</h3> None declared
Intramyocardial injection of a fully synthetic hydrogel attenuates left ventricular remodeling post myocardial infarction
Authors: Yasumoto Matsumura, Yang Zhu, Hongbin Jiang, Antonio D'Amore, Samuel K. Luketich, Verena Charwat, Tomo Yoshizumi, Hideyoshi Sato, Brenda Yang, Takafumi Uchibori, Kevin E. Healy, William R. Wagner
Journal: Biomaterials (2019)
Impaired Regeneration Potential in Urinary Stem Cells Diagnosed from the Patients with Diabetic Nephropathy
Authors: Geng Xiong, Weiqing Tang, Deying Zhang, David He, Guanghui Wei, Antony Atala, Xing-Jie Liang, Anthony J. Bleyer, Michael E. Bleyer, Jie Yu, Joseph A. Aloi, Jian-Xing Ma, Cristina M. Furdui, Yuanyuan Zhang
Journal: Theranostics (2019)

Stem cells present in urine possess regenerative capacity to repair kidney injury.However, the unique characteristics of urinary stem cells (USC) from patients with diabetic nephropathy (d-USC) are unknown.The goal of this study was to investigate stemness properties in cell phenotype and regenerative potential of d-USC, compared to USC from healthy individuals.Methods: Thirty-six urine samples collected from patients (n=12, age range 60-75 years) with diabetic nephropathy (stages 3-4 stage chronic kidney disease [CKD]) were compared with 30 urine samples from healthy age-matched donors (n=10, age range 60-74 years).Results: There were approximately six times as many cells in urine samples from patients with diabetic nephropathy, including twice as many USC clones as healthy donors.However, approximately 70% of d-USC had weaker regenerative capacity as assessed by cell proliferation, less secretion of paracrine factors, weaker telomerase activity, and lower renal tubular epithelial differentiation potential compared to healthy controls.In addition, the levels of inflammatory factors (IL-1β and Cx43) and apoptotic markers (Caspase-3, and TUNEL) were significantly increased in d-USC compared to USC (p<0.01).Protein levels of autophagy marker (LC3-II) and mTOR signaling molecules (p-mTOR/mTOR, p-Raptor/Raptor and p-S6K1) were significantly lower in patient with diabetic nephropathy (p<0.01).Nevertheless, up to 30% of d-USC possessed similar regenerative capacity as USC from healthy donors.Conclusions: Regenerative performance of most d-USC was significantly lower than normal controls.Understanding the specific changes in d-USC regeneration capability will help elucidate the pathobiology of diabetic nephropathy and lead to prevent USC from diabetic insults, recover the stemness function and also identify novel biomarkers to predict progression of this chronic kidney disease.
Home visits for uncontrolled asthma among low-income adults with patient portal access
Authors: Andrea J. Apter, A. Russell Localio, Knashawn H. Morales, Xiaoyan Han, Luzmercy Perez, Alyssa N. Mullen, Marisa Rogers, Heather Klusaritz, John T. Howell, Maryori N. Canales, Tyra Bryant-Stephens
Journal: Journal of Allergy and Clinical Immunology (2019)
PS1446 THE ROLE OF THE THROMBOPOIETIN RECEPTOR (MPL) IN JAK2V617F‐POSITIVE MYELOPLROLIFERATIVE NEOPLASMS
Authors: K. Behrens, E.M. Viney, T.A. Willson, J.J. Babon, N.A. Nicola, W.S. Alexander
Journal: HemaSphere (2019)

Background: Constitutive activation of the Jak/Stat signalling pathway is a hallmark of Myeloproliferative Neoplasms (MPN), with 60–90% of patients carrying the activating JAK2 mutation, JAK2 V617F . Several studies suggest expression of a type I cytokine receptor is essential for JAK2 V617F ‐mediated transformation, but the precise contribution of such receptors is unresolved. Aims: Here we investigate the functional role of Mpl in JAK2 V617F ‐driven MPN. Methods: Mpl mutants lacking various functional domains were screened for their capacity to support JAK2 V617F ‐mediated factor independence in BaF/3 cells. Using CRISPR/CAS9 genome editing Mpl‐mutant mice were generated to extend these findings to an in vivo model of JAK2 V617F MPN. Results: In vitro studies confirmed that Mpl expression was required for JAK2 V617F ‐induced transformation, but identified a Mpl truncation mutant retaining the JAK2‐interaction domain, but lacking the C‐terminus (Mpl‐IC36), typically associated with Stat5 binding, to be sufficient to support JAK2 V617F ‐induced transformation. Interestingly, Stat5‐phosphorylation was maintained. In contrast, deletion of the entire cytoplasmic receptor domain abrogated Stat5 phosphorylation and factor‐independent proliferation. In vivo Mpl‐wt;JAK2 V617F mice exhibited the thrombocytosis and erythrocytosis typical of MPN, while Mpl deficiency abrogated thrombocytosis but sustained high red blood cell counts. Although the Mpl‐IC36 receptor was sufficient for JAK2 V617F ‐induced factor independence in BaF/3 cells, Mpl‐IC36;JAK2 V617F mice did not develop thrombocytosis, indeed platelet counts were similar to those in Mpl null mice. This underlines differences that may emerge from in vitro and in vivo systems and highlights the important role of the Mpl cytoplasmic region for JAK2 V617F ‐mediated signalling. Summary/Conclusion: JAK2 V617F requires Mpl to induce transformation. While a Mpl truncation mutant retaining the JAK2‐interaction domain, but lacking the C‐terminus (Mpl‐IC36) was sufficient to induce JAK2 V617F ‐mediated cytokine independence in BaF/3 cells in vitro, this receptor was insufficient for development of thrombocytosis in JAK2 V617F mouse model. These results suggest that the role of Mpl in JAK2 V617F ‐induced MPN extends beyond a simple scaffold for active JAK2 and that signalling from the Mpl C‐terminal domain is required in vivo .
Author Correction: A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip
Authors: Sasan Jalili-Firoozinezhad, Francesca S. Gazzaniga, Elizabeth L. Calamari, Diogo M. Camacho, Cicely W. Fadel, Amir Bein, Ben Swenor, Bret Nestor, Michael J. Cronce, Alessio Tovaglieri, Oren Levy, Katherine E. Gregory, David T. Breault, Joaquim M. S. Cabral, Dennis L. Kasper, Richard Novak, Donald E. Ingber
Journal: Nature Biomedical Engineering (2019)
SAT0464 HEPATITIC SAFETY OF ANTI-TUBERCULOUS TREATMENT IN SPONDYLODISCITIS
Authors: Aicha Ben Tekaya, Khaoula Zouaoui, Rawdha Tekaya, Olfa Saidane, Mohamed Ben Hammamia, Ines Mahmoud, Leila Abdelmoula
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Tunisia is considered as a country with high tuberculosis endemicity. The anti-tuberculous treatment is quite long and binding and requires close hepatic monitoring. <h3>Objectives:</h3> The purpose of this study was to highlight the hepatitic safety of anti-tuberculous treatment in tuberculous spondylodiscitis. <h3>Methods:</h3> This is a retrospective descriptive study, over 20 years (1999-2019) collating cases of tuberculous spondylodiscitis in a rheumatology department. We studied the epidemiological, clinical, radiological and therapeutic aspects. <h3>Results:</h3> Our study included 62 patients, 35 women and 27 men. Mean age was 56 years [16-86]. The diagnosis delay averaged 5.59 months [0.23-24]. Tuberculous contact was noted in 11.3% of the cases. Neurological abnormalities were noted in 16,1% of cases with spine compression in 3,22%. The tuberculin skin test was positive in 29 cases and the Koch bacillus investigations in the sputum and the urine were positive in only 3 patients. Magnetic resonance imaging was performed in 71% of the patients, and mainly showed images of disc destruction with images of abscess, epiduritis and epidural extension. Infectious spondylodiscitis affected the lumbar spine in 66.1% of the cases, the dorsal spine in 14.51% of the cases and the cervical spine in 6.55% of the cases. It was bi-staged in 19.35% of the cases and bifocal in 17.74% of the cases. Disco-vertebral biopsy was performed for 72.5% of patients and helped to make the diagnosis in 33.87% of the cases. All patients have received anti-tuberculosis treatment based on rifampicin, pyrazinamide, ethambutol and Isoniazid for an average duration of 2.8 months. Following the initial 4-drug regimen, most patients continued to receive a two-drug regimen with RMP and INH for a mean duration of nine months. Hepatotoxicity was seen in 13% : 11.4% of the patients had a history of cholestasis due to TB treatment, Only 2% of the patients had cytolysis. We nedded then to modify the treatment in 3,22%, and switch to triple anti-TB therapy based on Isoniazid, Rifampicin and ethambutol with a favorable evolution. No cases of hepatic insufficiency were noted. <h3>Conclusion:</h3> In our study, we note 8 cases of hepatotoxicity. The diagnosis of tuberculous spondylodiscitis requires urgent treatment with anti-tuberculosis antibiotics. However, it should be kept in mind that this treatment can lead to severe and life-threatening hepatotoxicity. Thus a rigorous monitoring of the treatment will be required. <h3>Disclosure of Interests:</h3> None declared
Natural history and cell of origin of TCF3-ZNF384 and PTPN11 mutations in monozygotic twins with concordant BCP-ALL
Authors: Clara Bueno, J. Ramón Tejedor, Rachael Bashford-Rogers, Laura González-Silva, Rafael Valdés-Mas, Antonio Agraz-Doblás, Rafael Díaz de la Guardia, Jordi Ribera, Lurdes Zamora, Chrystele Bilhou-Nabera, Nassera Abermil, Hélène Guermouche, Elodie Gouache, Guy Leverger, Mario F. Fraga, Agustín F. Fernández, Paola Ballerini, Ignacio Varela, Pablo Menendez
Journal: Blood (2019)