tbuckley/cabot-search huggingface dataset:
CRISPR-Induced Deletion with SaCas9 Restores Dystrophin Expression in Dystrophic Models In Vitro and In Vivo
Authors: Benjamin L. Duchêne, Khadija Cherif, Jean-Paul Iyombe-Engembe, Antoine Guyon, Joel Rousseau, Dominique L. Ouellet, Xavier Barbeau, Patrick Lague, Jacques P. Tremblay
Journal: Molecular Therapy (2018)

Duchenne muscular dystrophy (DMD), a severe hereditary disease affecting 1 in 3,500 boys, mainly results from the deletion of exon(s), leading to a reading frameshift of the DMD gene that abrogates dystrophin protein synthesis. Pairs of sgRNAs for the Cas9 of Staphylococcus aureus were meticulously chosen to restore a normal reading frame and also produce a dystrophin protein with normally phased spectrin-like repeats (SLRs), which is not usually obtained by skipping or by deletion of complete exons. This can, however, be obtained in rare instances where the exon and intron borders of the beginning and the end of the complete deletion (patient deletion plus CRISPR-induced deletion) are at similar positions in the SLR. We used pairs of sgRNAs targeting exons 47 and 58, and a normal reading frame was restored in myoblasts derived from muscle biopsies of 4 DMD patients with different exon deletions. Restoration of the DMD reading frame and restoration of dystrophin expression were also obtained in vivo in the heart of the del52hDMD/mdx. Our results provide a proof of principle that SaCas9 could be used to edit the human DMD gene and could be considered for further development of a therapy for DMD.
Radiopaque Short Pancreatic Stents Reliably Migrate in Nearly All Patients When Inserted for Prevention of Pancreatitis
Authors: Michael J. Clores, Juan Carlos Bucobo, Lionel S. D’Souza, Eduardo J. Quintero, Demetrios J. Tzimas, Jonathan M. Buscaglia
Journal: Clinical Gastroenterology and Hepatology (2019)
SAT0424 PHENOTYPE OF PATIENTS WITH EARLY ONSET GOUT
Authors: Julia Herrou, Omar Al Tabaa, Etienne Gaix-Fontaine, Pascal Richette, Thomas Bardin, Frederic Lioté, Aline Frazier, Hang Korng Ea
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Gout is a frequent inflammatory arthritis in men after 45 years old. In this common (CG) form, gout is associated with comorbidities (CMs) including metabolic syndrome, hypertension, type 2 diabetes (T2D), obesity, chronic kidney disease and cardiovascular (CV) diseases. In contrast, very few data are available for early onset gout (EOG), defined as first flare before 30 years old. <h3>Objectives:</h3> The aim of this study was to compare gout characteristics and CMs between EOG and CG. <h3>Methods:</h3> We retrospectively included all gout patients (pts) with ineffective ULT who were referred to our department between 2014 and 2018, and who had at least one visit between 9 and 15 months after first visit. At baseline, ineffective ULT was defined by a serum urate level (SUL) above target (&gt; 360 μmol/L). Demographic characteristics, gout history and CMs, treatments were systematically recorded. <h3>Results:</h3> Among 213 pts, 39 (18.3%) had experienced a first gout flare before 30 years old. Pts and gout characteristics are summarized in table 1. Mean age of first flare in EOG was 24.8 (± 5.5) years. Familial history of gout was more frequent in EOG than in CG (60.6 vs 24.6%). First flare involved the 1<sup>st</sup> metatarsophalangeal joint in 70% of EOG pts. EOG pts had more severe gout than CG pts: longer disease duration (p&lt;0.0001), more flares in the last 12 months (p&lt;0.0001), more tophi (p=0.005) and higher febuxostat (FBX) dosage (p=0.02) to achieve SUL target. Pts with CG had more CMs than EOG pts: CV diseases, hypertension, T2D, dyslipidemia and kidney transplantation. Non-alcoholic fatty liver disease was more frequent in EOG than CG (61.1 vs 24.1%). At final visit, 62.8 and 67.9% of EOG and CG patients, respectively, achieved SUL target (p=0.56). Proportion of pts taken ULT was similar in both groups as well as proportion of pts treated with allopurinol or FBX. <h3>Conclusion:</h3> In conclusion, EOG is more severe and EOG pts have less CMs. Moreover, EOG has a higher inheritability trait than CG patients suggesting different pathological mechanisms. <h3>Disclosure of Interests:</h3> Julia Herrou: None declared, Omar Al Tabaa: None declared, Etienne Gaix-Fontaine: None declared, Pascal Richette Consultant for: Grunenthal, Horizon, Speakers bureau: AstraZeneca, Grunenthal, Thomas Bardin Consultant for: Astrazeneca, Grunenthal, Horizon, Novartis, Speakers bureau: Astella, AstraZeneca, Grunenthal., Frederic Lioté Grant/research support from: institutional grants from Grunenthal, Ipsen Pharma/Menarini, Novartis, SOBI for the European Crystal Network Workshops, Consultant for: Grunenthal, Novartis, Aline Frazier: None declared, Hang Korng Ea: None declared
Abstract 14668: Patient Perceptions of Care and Outcomes in the Post-Myocardial Infarction Population
Authors: Jennifer A Rymer, Shuang Li, Anita Y Chen, Deirdre Mylod, Gail Nellans, Tracy Y Wang
Journal: Circulation (2018)

Background: While higher in-hospital care quality is associated with greater patient satisfaction, the relationship between patient experience and post-discharge outcomes is unclear for patients wi...
NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk
Authors: Jack Antel, Maria Ban, Sergio Baranzini, Lisa Barcellos, Nadia Barizzone, Ashley Beecham, Tone Berge, Luisa Bernardinelli, David Booth, Steffan Bos, Dorothea Buck, Mariusz Butkiewicz, Elisabeth G. Celius, Manuel Comabella, Alastair Compston, Katrina Dedham, Chris Cotsapas, Sandra D’ Alfonso, Phil De Jager, Benedicte Dubois, Pierre Duquette, Bertrand Fontaine, Christiane Gasperi, Elia Gil, An Goris, Pierre Antoine Gourraud, Christiane Graetz, Alexandra Gyllenberg, Georgios Hadjigeorgiou, David Hafler, Deanna Hribko, Jonathan Haines, Hanne Harbo, Stephen Hauser, Shannon Warto, Clive Hawkins, Bernhard Hemmer, Roland Henry, Rogier Hintzen, Dana Horakova, Adrian Ivinson, Melissa Howard, Ilijas Jelcic, Belinda Kaskow, Jun-Ichi Kira, Pavlina Kleinova, Ingrid Kockum, Karolina Kucerova, Christina Lill, Felix Luessi, Sunny Malhotra, Roland Martin, Filippo Martinelli, Takuya Matsushita, Cristin McCabe, Jacob McCauley, Julia Mescheriakkova, Mitja Mitrovic, Stine-Marit Moen, Xavier Montalban, Mark Muhlau, Yuri Nakmura, Jorge Oksenberg, Tomas Olsson, Annette Oturai, Aarno Palotie, Nikolaos Patsopoulos, Jana Pavlicova, Peggy Pericak-Vance, Fredrik Piehl, Isabelle Rebeix, John Rioux, Janna Saarela, Stephen Sawcer, Finn Sellebjerg, Helle Bach Sondergaard, Per Soelberg Sorensen, Mireia Sospedra, Anne Spurkland, Graeme Stewart, Bruce Taylor, Andre Uitterlinden, Cornelia Van Duijn, Frauke Zipp
Journal: Neuron (2016)
Abstract 13323: Impact of Transcatheter Aortic Valve Replacement on the Mitral Valve Apparatus and Mitral Regurgitation: A Real-Time Three-Dimensional Transesophageal Echocardiography Study
Authors: Kentaro Shibayama, Kenji Harada, Hirotsugu Mihara, Jun Tanaka, Javier Berdejo, Swaminatha V Gurudevan, Robert Siegel, Hasan Jilaihawi, Raj R Makkar, Takahiro Shiota
Journal: Circulation (2013)

Backgrounds: The impact of transcatheter aortic valve replacement (TAVR) on the mitral valve apparatus and factors influencing reduction of mitral regurgitation (MR) with or without mitral leaflet ...
PB2035 ISAVUCONAZOLE AS PROPHYLAXIS AGAINST INVASIVE FUNGAL INFECTIONS IN STEM CELL TRANSPLANT PATIENTS: A DESCRIPTIVE SINGLE CENTER EXPERIENCE.
Authors: S.F. Pinzon, V.M. Marta, I. Izquierdo, A. Aules, E. Salvador, A. Garcia Ortego, R. Diez, P. Delgado
Journal: HemaSphere (2019)

Background: Isavuconazole is a novel triazole antifungal approved for treating invasive aspergillosis and mucormycosis with predictable pharmacokinetics compared to its counterparts; the handling of interactions with other medications is easier, which is the most important advantage of this antifungal. The aim of our study is to describe the experience with this Triazole in prophylaxis in our hospital. Aims: The aim of this study its to describe our experiencie with Isovuconazole. Methods: A retrospective review from the patients undergoing allogenic stem cell transplantation who received Isavuconazole in prophylaxis was performed. We analyze the demographic data and the risk factors related to the host, disease, treatment and the transplant. Results: From a sample of 6 patients with a main age of 52 age years, equal sex ratio, five patients have an acute myeloid leukemia (ALM) and one patient a myelodysplastic syndrome (MDS), all the patients has at least one high risk factor for the development of invasive fungal infections (IFI), described in the table 1. All of them was taking corticosteroids due to chronic/acute GVHD and one patient because of an autoimmune disease. All patients were treated with oral Isavuconazole at 200 mg per day at least 14 days for prophylaxis; the reasons to choose Isavuconazole were elevated liver transaminases in four cases and Posaconazole intolerance in two patients. Serum detection of galactomannan was performed for all patients every week during antifungal therapy and all the results were negative. Summary/Conclusion: Although the efficacy and safety of Isavuconazole, there is no indication in the technical sheet for prophylaxis with this triazole. At this time, none of our patients developed an IFI or intolerance to treatment. There are few studies that evaluate prophylaxis, most related to the experience in solid organ transplantation, but it is not known what is happening in the real world of hematological diseases. In our experience seems to be a useful and safe drug, however, more studies are needed to verify this hypothesis. image
Abstract 17344: Benefit of Left Atrial Appendage Electrical Isolation for Persistent and Long-Standing Persistent Atrial Fibrillation. A Systematic Review and Meta-Analysis
Authors: Jorge Romero, Ricardo Avendano, Gregory F Michaud, William Stevenson, David F Briceno, Juan C Diaz, Saurabh Kumar, Stefano Bordignon, Mario Garcia, Andrea Natale, Luigi Di Biase
Journal: Circulation (2017)

Background: The results of the effect of left atrial appendage electrical isolation (LAAEI) on long-term procedure outcome in patients with non-paroxysmal atrial fibrillation(AF) has been described...
Preoperative risk assessment model for identification of lymph node metastasis in early cervical cancer.
Authors: Seung-Hyuk Shim, Dae-Yeon Kim, Shin-Wha Lee, Jeong-Yeol Park, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam
Journal: Journal of Clinical Oncology (2013)

5600 Background: The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with early cervical cancer. Methods: The medical records of 504 patients with early cervical cancer who underwent hysterectomy and pelvic/paraaortic lymphadenectomy between 2007and 2012 in our center were retrospectively reviewed. According to the order of surgery performed, data between 2007 and 2010 were allocated to a model development cohort (n=314), and data between 2011 and 2012 were allocated to an external validation cohort (n=190). By using preoperative clinicopathologic data, magnetic resonance imaging (MRI) data, and positron emission/computed tomography (PET/CT) data, a multivariate logistic model was created. Based on this model, predictive nomogram was developed and externally validated. Results: Age, tumor size measured by MRI, and lymph node metastasis on PET/CT were found to be independent risk factors for nodal metastasis. Developed nomogram incorporating these three predictors showed good discrimination and calibration, with a bootstrap-adjusted concordance index of 0.772. Also, the validation set showed good discrimination with a bootstrap-adjusted concordance index of 0.783. Conclusions: We have developed a robust model to predict lymph node metastasis in patients with early cervical cancer. This new tool may be useful to clinicians and patients when deciding lymphadenectomy and maybe useful in designing clinical trials. [Table: see text]
PB2307 SICKLE CELL DISEASE PATIENTS HAVE NORMAL NEUTROPHIL OXIDATIVE BURST RESPONSE
Authors: M. El‐Samahi, S. Makkeyah, M. Hamza, A. Abouelnour
Journal: HemaSphere (2019)

Background: Bacterial infections are a frequent cause of acute morbidity and sometimes mortality in sickle cell disease (SCD). Splenic dysfunction alone does not explain the susceptibility to specific organisms e.g., Staphylococcus aureus and Klebsiella as shown in some studies; suggesting that the splenic dysfunction is not the only explanation and that neutrophil dysfunction may be present. Neutrophils destroy microbes by producing a burst of reactive oxygen species (ROS) (respiratory burst) in response to bacterial components, as well as to phorbol‐myristate‐acetate (PMA). Some studies have shown that the state of chronic hemolysis in SCD impairs the ability to develop neutrophils to mount a bactericidal oxidative burst, and hence increasing susceptibility to bacterial infections. Aims: to assess the neutrophil oxidative burst in SCD patients and explore the relation to markers of hemolysis. Methods: Twenty‐seven hydroxyurea naïve children and adolescents with SCD (mean age 11.1 ± 3.9 years) were enrolled from Pediatric Hematology Clinic at Ain Shams University Children's Hospital. They were compared to 26 age‐ and sex‐matched healthy controls. Patients were studied stressing on transfusion history, chelation therapy, serum ferritin, hematological profile, markers of hemolysis and serum haptoglobin. Neutrophil oxidative burst assay was performed using DHR based flow cytometry. Results: Eleven (40%) out of the 27 patients had HBSS while 16 (60%) patients were sickle thalassemias. Six patients (22.2%) were splenectomized. Severe vaso‐occlusive crisis and acute chest syndrome were found in 22.2% and 18.5% of patients, respectively. Four (14.8%) patients had evidence of stroke. Bone fractures and avascular necrosis were found in 5.5% and 11.1 % of patients, respectively. Most of the studied patients were on chelation therapy, either as monotherapy or combined chelation (37% each). White blood cell count and reticulocytic count were significantly higher in SCD patients as compared to healthy controls (P = 0.03 and &lt;0.01 respectively). All subjects, whether SCD or controls showed a normal neutrophil oxidative burst response to PMA‐stimulation. Unstimulated and PMA stimulated rhodamine fluorescence were comparable in SCD patients and controls, indicating normal basal production of reactive oxygen species, and normal oxidative burst in SCD patients (P = 0.09). We did not demonstrate any correlation between markers of hemolysis including reticulocytic count, indirect bilirubin, LDH, serum haptoglobin and DHR response in the SCD group. Summary/Conclusion: Neutrophils in SCD patients can mount a normal oxidative burst in response to PMA stimulation. This data excludes the role of impaired neutrophil oxidative burst as a risk for bacterial infections in SCD.
AB0406 THE POTENT WEAPON FOR RHEUMATOID ARTHRITIS-INTERSTITIAL LUNG DISEASE : RITUXIMAB EXPERIENCES
Authors: Burak Karakaş, Mehmet Emin Derin, Fatih Albayrak, Ali Şahin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a common inflammatory disease with unknown etiology and systemic involvement (1). About 40% of RA patients have extraarticular involvement. Lung involvement is the most common extraarticular finding. The use of rituximab (RTX) in the treatment of rheumatoid arthritis- interstitial lung disease (RA-ILD) has been increasing in recent years (2). <h3>Objectives:</h3> To present our rituximab experience in patients with RA-ILD. <h3>Methods:</h3> Between April 2015 and April 2018, sixteen patients with RA-ILD who were followed up with RTX treatment in our university internal medicine-rheumatology department were included in this study. High resolution computed tomography (HRCT), carbon monoxide diffusion measurement (DLCO), pulmonary function test (PFT) and routine laboratory tests were examined. <h3>Results:</h3> The median age of the patients was 68 years (min: 52-max: 77). 4 patients (25%) were male and 12 (75%) patients were female. Four of our patients (25%) were active smokers. Non-specific interstitial pneumonia (NSIP) was seen in 10 (62.5%) patients and usual interstitial pneumonia (UIP) was seen in 6 (37.5%) patients. Before RTX, 8 patients were receiving methotrexate and 8 patients were using leflunomide. Four patients had anti-TNF (tumor necrosis factor) treatment. Median during treatment time was 6 months. Other features of the patients are summarized in Table 1. All patients had dyspnea with exertion before treatment. The Forced Vital Capacity (FVC) median was% 70 and DLCO was% 66. Although 2/16 patients received cyclophosphamide treatment, there was no clinical response and then RTX treatment was started. Protocol of treatment was every 6 months (days 0 and 15 days 1 g). After 6 months, FVC values improved with NSIP pattern (p= 0.04). There was no improvement in the UIP pattern but remained stable (Table 2). Clinically, patients' exertional dyspnea improved. There were no serious side effects in the follow-up of the patients. <h3>Conclusion:</h3> There is no valid guideline for RA-ILD treatment. Patient-based decision-making is important in the treatment of these patients. In recent years, RTX seems to be quite effective in RA-ILD. However, long-term and extensive studies are needed in terms of maintenance treatment and possible side effects. <h3>References</h3> [1] McInnes IB, G. Schett, The pathogenesis of rheumatoid arthritis. N Engl J Med 2011; 365: 2205-19. [2] Deborah Assayag, Joyce S. Lee, Talmadge E. Kıng, Jr., Rheumatoid Arthritis Associated Interstitial Lung Disease: A Review, MEDICINA (Buenos Aires) 2014; 72: 158-165 <h3>Key Words</h3> Rheumatoid Arthritis-Interstitial Lung Disease, Rituximab <h3>Disclosure of Interests:</h3> None declared
AB1377-HPR PATIENT ACTIVATION MEASURE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Laura Villarreal, Fernando Rodriguez, Pedro Santos-Moreno, Diana Buitrago-Garcia
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The Patient Activation Measure (PAM) is a 13-item measure that assesses patient knowledge, skill, and confidence for self-management. The measure was developed using Rasch analyses and is an interval level, unidimensional, Guttman-like measure. The current analysis is aimed at reducing the number of items in the measure while maintaining adequate precision(1). A Spanish adaptation of the scale was performed in 2017. <h3>Objectives</h3> To determine the level of activation, knowledge and skills for self-management in patients with Rheumatoid Arthritis <h3>Methods</h3> We performed a quantitative, observational, cross-sectional, and questionnaire-based study, convenience sampling was used. Participants were recruited in a specialized RA center, during a patients meeting. We applied the PAM-13 scale validated in Spanish. The scale has a score from 1 to 4 divided in four levels where level 1 represents a disengaged patient and suggests that the doctor is in charge of their health; level 2: the patient becomes aware but struggling; level 3: The patient is taking action and considers himself as a part of the healthcare team, and level 4 represents a patient that maintains behaviors and pushes forward. The maximum score is 52 points. <h3>Results</h3> 322 patients participated, 23 patients generated incomplete PAM scores (response rate 92%) and were excluded. From total 93% of patients were women. Mean age was 60 years 10; mean PAM-13 Was 19.83 6.16. In our study 68% of patients were in level 2 according to PAM-13 scale which means that they are becoming aware of their knowledge, skills and self-management but are still struggling. See table 1. In average 80% of patients answered each question to be in level 1 or 2, 15% in level 3 and only 5% in level 4. <h3>Conclusion</h3> This is the first study in our country where the Patient Activation Measure is applied in patients with rheumatoid arthritis. Thus, it might be useful to implement patient activation monitoring, since the level of activation is low in patients with RA. <h3>Disclosure of Interests</h3> Laura Villarreal: None declared, Fernando Rodriguez: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB, Diana Buitrago-Garcia: None declared
β6 integrinosis: a new lethal autosomal recessive ITGB6 disorder leading to impaired conformational transitions of the α<sub>V</sub>β6 integrin receptor
Authors: Patrick Weil, Rhea van den Bruck, Thomas Ziegenhals, Stefan Juranek, Daniel Goedde, Valerie Orth, Stefan Wirth, Andreas C Jenke, Jan Postberg
Journal: Gut (2019)

We read with interest the recent work by Schleier et al 1 demonstrating consequences of impaired α4β7 integrin-dependent gut homing of intestinal macrophages on wound healing, which fits well with own observations we have made in a case of congenital infantile intractable diarrhoea linked to impaired integrin receptors in intestinal epithelia (αVβ6). Specifically, a male dizygotic twin was delivered dystrophic (1715 g) at 36 weeks of gestational age and developed intractable diarrhoea within the following 2 months, contrary to his twin brother. Severe systemic infection or parasitosis was ruled out, but subsequently low-serum IgG and severe neutropenia occurred due to consumption of neutrophils during the prolonged diarrhoea. Eventually, he developed cholestatic hepatopathy and thrombocytopenia and died of uncontrollable GI, dermal haemorrhages and hepatic failure at 7 months of age. Extensive diagnostics included biopsies of liver, muscle, bone marrow, small intestine, the exclusion of known congenital diarrhoea reasons and immunodeficiencies by leucocyte FACS, CD40L expression, WASP staining, et cetera with no results.2 Familial anamnesis revealed similar fatalities of a sister and further cousins from the patient’s …
Abstract 08: Preterm Delivery and Maternal Cardiovascular Risk Factor Trajectories across the Life Course
Authors: Amanda R Markovitz, Eirin B Haug, Julie Horn, Abigail Fraser, Corrie Macdonald-Wallis, Kate Tilling, Pål R Romundstad, Bjørn Olav Åsvold, Janet W Rich-Edwards
Journal: Circulation (2017)

Introduction: Preterm delivery (&lt;37 weeks) predicts 2 to 3-fold greater risk of cardiovascular disease in mothers. Development of subclinical cardiovascular risk in these women prior to and following pregnancy is not well understood. Hypothesis: Women who deliver preterm have an adverse cardiovascular health profile even prior to pregnancy. Methods: Linked data from the population-based, longitudinal HUNT study (1984-2008) and the Medical Birth Registry of Norway (1967-2012) yielded clinical measurements and pregnancy outcomes for 23,179 parous women. Women had up to 3 measurements of body mass index, waist circumference, blood pressure, non-fasting lipids and glucose, and high-sensitivity C-reactive protein (hs-CRP) during a follow-up period between 20 years before first birth to 41 years after first birth. We used mixed effects linear spline models, adjusting for age, pre-pregnancy smoking, education, and time since last meal, to compare risk factor trajectories for women with preterm versus term/postterm first births. Results: Women with a preterm first birth (n=1,402, 6%) had significantly higher triglyceride (Figure 1 A) and glucose levels prior to pregnancy. They also experienced steeper increases in systolic and diastolic blood pressure, non-HDL cholesterol, triglycerides, and hs-CRP from first birth to age 50 compared to women who delivered at term/post-term (Figure 1 A,B). Measures of adiposity were similar throughout the life course. Conclusions: These results are consistent with the hypothesis that preterm birth is an early marker of cardiometabolic impairment. A history of preterm birth may predict high cardiovascular risk well before the development of traditional risk factors.