tbuckley/cabot-search huggingface dataset:
Extramedullary Relapsed Multiple Myeloma Treatment With 177Lu-Labeled CXCR4 Endoradiotherapy and Dosimetric Results
Authors: Mehmet Onur Demirkol, Ahu Özkan, Burcu Uçar, Hans-Jürgen Wester, Burhan Ferhanoğlu
Journal: Clinical Nuclear Medicine (2021)

Abstract We created our first national clinical protocol of 177 Lu-CXCR4 therapy for patient who have failed to respond to current therapy options. We also calculated the kidney, liver, and tumor dosimetry. The kidney's mean absorbed dose was calculated to be 0.45 Gy/GBq, the calculated radiation absorbed dose of the liver was 0.63 Gy/GBq, and the radiation absorbed doses of the tumors vary between 9.2 and 82 Gy/GBq. 177 Lu-CXCR4 therapy produced a promising clinical response in our patient in acceptable radiation dose limits as a treatment option in heavily pretreated patients with advanced multiple myeloma.
Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis
Authors: Amy C. Sturm, Rebecca Truty, Thomas E. Callis, Sienna Aguilar, Edward D. Esplin, Sarah Garcia, Eden V. Haverfield, Ana Morales, Robert L. Nussbaum, Susan Rojahn, Matteo Vatta, Daniel J. Rader
Journal: JAMA Cardiology (2021)

Familial hypercholesterolemia (FH) is the most common inherited cardiovascular disease and carries significant morbidity and mortality risks. Genetic testing can identify affected individuals, but some array-based assays screen only a small subset of known pathogenic variants.To identify the number of clinically significant variants associated with FH that would be missed by an array-based, limited-variant screen when compared with next-generation sequencing (NGS)-based comprehensive testing.This cross-sectional study compared comprehensive genetic test results for clinically significant variants associated with FH with results for a subset of 24 variants screened by a limited-variant array. Data were deidentified next-generation sequencing results from indication-based or proactive gene panels. Individuals receiving next-generation sequencing-based genetic testing, either for an FH indication between November 2015 and June 2020 or as proactive health screening between February 2016 and June 2020 were included. Ancestry was reported by clinicians who could select from preset options or enter free text on the test requisition form.Number of pathogenic or likely pathogenic (P/LP) variants identified.This study included 4563 individuals who were referred for FH diagnostic testing and 6482 individuals who received next-generation sequencing of FH-associated genes as part of a proactive genetic test. Among individuals in the indication cohort, the median (interquartile range) age at testing was 49 (32-61) years, 55.4% (2528 of 4563) were female, and 63.6% (2902 of 4563) were self-reported White/Caucasian. In the indication cohort, the positive detection rate would have been 8.4% (382 of 4563) for a limited-variant screen compared with the 27.0% (1230 of 4563) observed with the next-generation sequencing-based comprehensive test. As a result, 68.9% (848 of 1230) of individuals with a P/LP finding in an FH-associated gene would have been missed by the limited screen. The potential for missed findings in the indication cohort varied by ancestry; among individuals with a P/LP finding, 93.7% (59 of 63) of self-reported Black/African American individuals and 84.7% (122 of 144) of Hispanic individuals would have been missed by the limited-variant screen, compared with 33.3% (4 of 12) of Ashkenazi Jewish individuals. In the proactive cohort, the prevalence of clinically significant FH variants was approximately 1:191 per the comprehensive test, and 61.8% (21 of 34) of individuals with an FH-associated P/LP finding would have been missed by a limited-variant screen.Limited-variant screens may falsely reassure the majority of individuals at risk for FH that they do not carry a disease-causing variant, especially individuals of self-reported Black/African American and Hispanic ancestry.
Abrupt termination of the 2019/20 influenza season following preventive measures against COVID-19 in Denmark, Norway and Sweden
Authors: Hanne-Dorthe Emborg, AnnaSara Carnahan, Karoline Bragstad, Ramona Trebbien, Mia Brytting, Olav Hungnes, Emma Byström, Lasse S Vestergaard
Journal: Eurosurveillance (2021)

Background In mid-March 2020, a range of public health and social measures (PHSM) against the then new coronavirus disease (COVID-19) were implemented in Denmark, Norway and Sweden. Aim We analysed the development of influenza cases during the implementation of PHSM against SARS-CoV-2 in the Scandinavian countries. Method Based on the established national laboratory surveillance of influenza, we compared the number of human influenza cases in the weeks immediately before and after the implementation of SARS-CoV-2 PHSM by country. The 2019/20 influenza season was compared with the five previous seasons. Results A dramatic reduction in influenza cases was seen in all three countries, with only a 3- to 6-week duration from the peak of weekly influenza cases until the percentage dropped below 1%. In contrast, in the previous nine influenza seasons, the decline from the seasonal peak to below 1% of influenza-positive samples took more than 10 weeks. Conclusions The PHSM against SARS-CoV-2 were followed by a dramatic reduction in influenza cases, indicating a wider public health effect of the implemented measures.
Setting up laboratory-based antimicrobial resistance surveillance in low- and middle-income countries: lessons learned from Georgia
Authors: Lile Malania, Inge Wagenaar, Onur Karatuna, Arjana Tambic Andrasevic, David Tsereteli, Marine Baidauri, Paata Imnadze, Saskia Nahrgang, Carolien Ruesen
Journal: Clinical Microbiology and Infection (2021)
POS0916 SAFETY OF BIOLOGIC TREATMENTS IN SOLID ORGAN TRANSPLANT RECIPIENTS: A SYSTEMATIC REVIEW
Authors: M. Frederic, W. V. Delphine, C. Prati, D. Wendling, F. Verhoeven
Journal: Annals of the Rheumatic Diseases (2021)

Background: The management of a broad spectrum of autoimmune/inflammatory diseases has been transformed with the development of biological treatments. However, little is known about their use in solid organ transplant recipients, a group of patients with high risk of serious infections and malignancies. Objectives: To evaluate complications occurring with biologic treatments in solid-organ transplant recipients. Methods: A systematic review of the literature was performed on the PubMed including Medline, Embase and Cochrane databases, up to 01/10/2020, to identify published case reports/series regarding the use of biologic treatments in solid organ transplant recipients in the context of chronic inflammatory diseases. Collected data were patient’s characteristics (age, sex, reason for transplantation, antirejection regimen, type of biological treatment used, autoimmune/inflammatory disease treated, time between transplantation and biotherapy initiation, treatment duration) and their reported complications (deaths, infections, malignancies, graft dysfunction). Results: 55 papers were included, representing 177 patients (131 liver, 42 kidney, 3 heart, and 1 liver-kidney transplant recipients). Inflammatory bowel diseases represented largely the most common indication of biologic treatment initiation (80.2%), followed by rheumatic diseases (7.3%), hereditary periodic fever syndromes (6.2%) and psoriasis (5.1%). Anti-TNFα were mainly used (81.4%) before anti- α4β7 integrin Vedolizumab (23.7%) and anti-IL1R Anakinra (7.3%). 25/177 patients had several lines of different treatments. Median treatment duration was 13.5 months. Infections occurred in 48 patients (27.1%) through 76 recorded flares (mostly bacterial 68.4% and viral 19.7%). No therapeutic or epidemiological factor was associated with the occurrence of an infection. 16 patients (9.0%) developed malignancies, especially colorectal (4 cases, 2.3%) and skin cancers (4 cases, 2.3%) or Post-transplantation lymphoproliferative disorders (3 cases, 1.7%). Acute graft rejections occurred in 5 patients (2.8%), mostly in kidney transplants (4/5). Among a total of 177 patients, 6 deaths were identified (3.4%). Conclusion: This review gathers, to our knowledge, the largest number of published case series/reports about the use of biological treatments in solid organ transplant recipients, providing data about their safety. Caution must be taken about eventual publication bias and the necessity of further head-to-head analysis comparing complications occurring in solid organ transplant recipients cohorts with and without biologic treatments. Disclosure of Interests: None declared
Effects of pregnancy on chronic urticaria: Results of the PREG‐CU UCARE study
Authors: Emek Kocatürk, Mona Al‐Ahmad, Karoline Krause, Ana M. Gimenez‐Arnau, Simon Francis Thomsen, Niall Conlon, Alexander Marsland, Ekin Savk, Roberta F. Criado, Inna Danilycheva, Daria Fomina, Kiran Godse, Maryam Khoshkhui, Aslı Gelincik, Ece Nur Degirmentepe, Semra Demir, Luis Felipe Ensina, Alicja Kasperska‐Zajac, Michael Rudenko, Solange Valle, Iris Medina, Andrea Bauer, Zuotao Zhao, Petra Staubach, Laurence Bouillet, Özlem Su Küçük, Can Ateş, Marcus Maurer
Journal: Allergy (2021)

Chronic urticaria (CU) predominantly affects women, and sex hormones can modulate disease activity in female CU patients. As of now, the impact of pregnancy on CU is largely unknown.To analyze the course and features of CU during and after pregnancy.PREG-CU is an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47-item questionnaire completed by CU patients, who became pregnant within the last 3 years.A total of 288 pregnancies of 288 CU patients from 13 countries were analyzed (mean age at pregnancy: 32.1 ± 6.1 years, duration of CU: 84.9 ± 74.5 months; CSU 66.9%, CSU + CIndU 20.3%, CIndU 12.8%).During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged.CU exacerbations most commonly occurred exclusively during the third trimester (in 34 of 124 patients; 27.6%) or the first (28 of 124; 22.8%). The risk factors for worsening of CU during pregnancy were having mild disease and no angioedema before pregnancy, not taking treatment before pregnancy, CIndU, CU worsening during a previous pregnancy, treatment during pregnancy, and stress as a driver of exacerbations. After giving birth, urticaria disease activity remained unchanged in 43.8% of CU patients, whereas 37.4% and 18.1% experienced worsening and improvement, respectively.These results demonstrate the complex impact of pregnancy on the course of CU and help to better counsel patients who want to become pregnant and to manage CU during pregnancy.
In obesity with T2DM, biliopancreatic diversion increased T2DM remission vs. medical and lifestyle therapy at 10 y
Authors: Shohinee Sarma, Lorraine L. Lipscombe
Journal: Annals of Internal Medicine (2021)

Mingrone G, Panunzi S, De Gaetano A, et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2021;397:293-304. 33485454.
Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease
Authors: Raffaella Molteni, Riccardo Biavasco, Davide Stefanoni, Travis Nemkov, Jorge Domínguez-Andrés, Rob J. Arts, Ivan Merelli, Davide Mazza, Samuel Zambrano, Maddalena Panigada, Eleonora Cantoni, Isak W. Tengesdal, Philippe Maksud, Francesco Piras, Daniela Cesana, Laura Cassina, Gianfranco Distefano, Alessia Loffreda, Daniela Gnani, Giacomo De Luca, Alessandro Tomelleri, Corrado Campochiaro, Leo A. B. Joosten, Charles A. Dinarello, Anna Kajaste-Rudnitski, Julien Haroche, Simone Cardaci, Simone Cenci, Lorenzo Dagna, Claudio Doglioni, Marina Ferrarini, Elisabetta Ferrero, Alessandra Boletta, Angelo D’Alessandro, Eugenio Montini, Mihai G. Netea, Giulio Cavalli
Journal: Blood (2021)
Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles
Authors: Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Kento Kumon, Tomoko Tsumura, Masashi Hashimoto, Chiaki Yagi, Ryoma Sugimoto, Yuki Hamada, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara
Journal: Molecular Therapy (2021)

Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.
Abstract 11460: Prognostic Value of Periatrial Adipose Tissue and Thyroid Stimulating Hormone in Paroxysmal Atrial Fibrillation With Catheter Ablation
Authors: Masato Kawasaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Atsush Kikuchi, Tsutomu Kawai, Masahiro Seo, Makoto Abe, Jun Nakamura, Kyoko Yamamoto, Kiyomi Kayama, Kazuya Tanabe, Masatsugu Kawahira
Journal: Circulation (2019)

Background: Both the periatrial epicardial adipose tissue (EAT) and thyroid dysfunction (TD) are known to play an important role in progression of atrial fibrillation (AF). However, there is little...
STAT3 activation in large granular lymphocyte leukemia is associated with cytokine signaling and DNA hypermethylation
Authors: Daehong Kim, Giljun Park, Jani Huuhtanen, Bishwa Ghimire, Hanna Rajala, Richard Moriggl, Wing C. Chan, Matti Kankainen, Mikko Myllymäki, Satu Mustjoki
Journal: Leukemia (2021)

Abstract Large granular lymphocyte leukemia (LGLL) is characterized by somatic gain-of-function STAT3 mutations. However, the functional effects of STAT3 mutations on primary LGLL cells have not been studied in detail. In this study, we show that CD8+ T cells isolated from STAT3 mutated LGLL patients have high protein levels of epigenetic regulators, such as DNMT1, and are characterized by global hypermethylation. Correspondingly, treatment of healthy CD8+ T cells with IL-6, IL-15, and/or MCP-1 cytokines resulted in STAT3 activation, increased DNMT1, EZH2, c-MYC, l-MYC, MAX, and NFκB levels, increased DNA methylation, and increased oxidative stress. Similar results were discovered in KAI3 NK cells overexpressing gain-of-function STAT3 Y640F and STAT3 G618R mutants compared to KAI3 NK cells overexpressing STAT3 WT . Our results also confirm that STAT3 forms a direct complex with DNMT1, EZH2, and HDAC1. In STAT3 mutated LGLL cells, DNA methyltransferase (DNMT) inhibitor azacitidine abrogated the activation of STAT3 via restored SHP1 expression. In conclusion, STAT3 mutations cause DNA hypermethylation resulting in sensitivity to DNMT inhibitors, which could be considered as a novel treatment option for LGLL patients with resistance to standard treatments.
Abstract 16362: Impact of Morphine Treatment on Infarct Size and Reperfusion Injury in Acute Reperfused ST-Elevation Myocardial Infarction
Authors: Ingo Eitel, Thomas Stiermaier, Georg T Fuernau, Harald Langer, Steffen Desch, Suzanne de Waha, Juan Wang, Holger Thiele
Journal: Circulation (2019)

Introduction: Current evidence suggests an adverse effect of morphine on platelet inhibition induced by P2Y12 receptor antagonists and morphine application has been shown to be independently associ...
Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes
Authors: Xavier Rossello, Sergio Raposeiras-Roubin, Belén Oliva, Fátima Sánchez-Cabo, José M. García-Ruíz, Francisca Caimari, José M. Mendiguren, Enrique Lara-Pezzi, Héctor Bueno, Leticia Fernández-Friera, Antonio Fernández-Ortiz, Javier Sanz, Borja Ibanez, Valentin Fuster
Journal: Journal of the American College of Cardiology (2021)

The metabolic injury caused by protein glycation, monitored as the level of glycated hemoglobin (HbA1c), is not represented in most risk scores (i.e., Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease risk scale). The purpose of this study was to assess the association between HbA1c and the extent of subclinical atherosclerosis (SA) and to better identify individuals at higher risk of extensive SA using HbA1c on top of key cardiovascular risk factors (CVRFs). A cohort of 3,973 middle-aged individuals from the PESA (Progression of Early Subclinical Atherosclerosis) study, with no history of cardiovascular disease and with HbA1c in the nondiabetic range, were assessed for the presence and extent of SA by 2-dimensional vascular ultrasound and noncontrast cardiac computed tomography. After adjusting for established CVRFs, HbA1c showed an association with the multiterritorial extent of SA (odds ratio: 1.05, 1.27, 1.27, 1.36, 1.80, 1.87, and 2.47 for HbA1c 4.9% to 5.0%, 5.1% to 5.2%, 5.3% to 5.4%, 5.5% to 5.6%, 5.7% to 5.8%, 5.9% to 6.0%, and 6.1% to 6.4%, respectively; reference HbA1c ≤4.8%; p < 0.001). The association was significant in all pre-diabetes groups and even below the pre-diabetes cut-off (HbA1c 5.5% to 5.6% odds ratio: 1.36 [95% confidence interval: 1.03 to 1.80]; p = 0.033). High HbA1c was associated with an increased risk of SA in low-risk individuals (p < 0.001), but not in moderate-risk individuals (p = 0.335). Relative risk estimations using Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease predictors confirmed that inclusion of HbA1c modified the risk of multiterritorial SA in most risk categories. Routine use of HbA1c can identify asymptomatic individuals at higher risk of SA on top of traditional CVRFs. Lifestyle interventions and novel antidiabetic medications might be considered to reduce both HbA1c levels and SA in individuals without diabetes.
AB0784 SPINAL HYDATID CYST DISEASE: WHAT FEATURES IN SURGICAL DEPARTMENTS?
Authors: A. Dghaies, R. Dhahri, M. Slouma, L. Metoui, I. Gharsallah, R. Ayari, Y. Mallat, K. Amri, M. Aloui, Y. Arous
Journal: Annals of the Rheumatic Diseases (2021)

Background: Cystic echinococcosis (CE) is a zoonosis caused by the larve of Echinococcus granulosus. Cysts can develop in any part of the body, although the liver and lungs are most frequently involved. Bone echinococcosis is one of the rarest forms of the disease, accounting for 0.5 to 4.0% of all echinococcosis. Spinal cysts are disabling causing destruction similar to malignant bone lesions, with high risk of neurological deficit. Objectives: To increase awareness of this disease, the clinical data of eight patients with spinal CE were analyzed retrospectively. Methods: Clinical data of eight patients with spinal CE were analyzed retrospectively, collected over ten years on the department of orthopedics in the Military hospital of Tunis. Results: The mean age of the patients was 49 years. The median disease duration was five years. All patients presented with back pain and paresthesia without neurological deficit. Radicular pain was reported by two patients. The diagnosis of spinal CE was made after the diagnosis of visceral CE in two patients. Former X rays showed nonspecific abnormalities and patients were treated initially by symptomatic treatments based on paracetamol and nonsteroidal antiinflammatory drugs without any improvement. All of the patients needed Magnetic resonance imaging (MRI) to explore chronic back pain with paresthesia, revealing spinal CE. The typical MRI appearance is a multilocular cyst. Six patients had cervical and thoracic spinal cysts, one patient had a lumbar spinal cyst and one patient had cervical, thoracic and lumbar cysts. Further examinations with Computed tomography scans (CTscans) were needed before surgery for better examination bone destruction. All patients underwent surgery. Cysts were removed with spinal fixation. All the patients showed relapses and needed at least three surgical interventions. Conclusion: Bone echinococcosis is rare and often misdiagnosed. Radiographic and CT images lack disease-specific characteristics whereas MRI images offers a greater chance of direct diagnosis. Treatment of spinal hydatid disease is entirely surgical with high risk of relapses. Disclosure of Interests: None declared
Prisons as ecological drivers of fitness-compensated multidrug-resistant Mycobacterium tuberculosis
Authors: Sebastian M. Gygli, Chloé Loiseau, Levan Jugheli, Natia Adamia, Andrej Trauner, Miriam Reinhard, Amanda Ross, Sonia Borrell, Rusudan Aspindzelashvili, Nino Maghradze, Klaus Reither, Christian Beisel, Nestani Tukvadze, Zaza Avaliani, Sebastien Gagneux
Journal: Nature Medicine (2021)
Abstract 15011: In-Hospital Outcomes of Acute Pericarditis Patients With and Without Autoimmune Disease
Authors: Yasser Al-khadra, Fahed Darmoch, Ziad SayedAhmad, Homam Moussa Pacha, Mohamad Soud, Massimo Imazio, Allan L Klein, M Chadi M Alraies
Journal: Circulation (2019)

Background: Pericarditis accounts for a considerable number of chest pain visits to the emergency department. The association between acute pericarditis (AP) and autoimmune diseases has been identi...
AB0123 ANXIETY AND DEPRESSION DURING RHEUMATOID ARTHRITIS
Authors: L. Ben Ammar, S. Rekik, S. Boussaid, S. Jemmali, E. Cheour, H. Sahli, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2021)

Background: Although the management of rheumatoid arthritis (RA) has been booming since the advent of biological treatments, the consequences of this disease remain multiple, both physical and psychological. Objectives: The aim of our work was to investigate the factors influencing anxiety and depression in RA. Methods: This was a cross-sectional study of 49 RA patients. We used the Hospital Anxiety and Depression scale (HAD) to assess anxiety disorders. Results: We included 24 women and 5 men with an average age of 54.1 years. Sixty-nine percent of patients were unemployed and 81% had health insurance coverage. RA had been evolving for an average of 11.43 ± 7.32 years and the mean time to diagnosis was 2.35 years. It was erosive in 93.8% of cases. An atlanto-axial dislocation was found in 4.1% of cases and coxitis in 8.2% of cases. Eighty-three percent of patients were on cs-DMARDs and 14.2% were on biotherapy. Most patients had low active disease (53%) with a mean DAS28CRP score of 2.74 ± 0.81. Twelve percent of patients had a probable anxiety and 18% had a probable depression. A long delay in diagnosis was associated with a higher risk of anxiety disorders. Working patients had a lower risk of depression while patients from rural areas had a higher risk. The risk of anxiety and depression disorders was associated with increased VAS pain, EGP, and DAS28. In the multivariate study, EGP was the independent risk factor for the development of anxiety and depression disorders. Conclusion: Anxiety and depression disorders are a frequent yet underestimated consequence in RA. Appropriate care in psychiatry is required as soon as the diagnosis is announced. Disclosure of Interests: None declared