tbuckley/cabot-search huggingface dataset:
POS0356 THE RELATIONSHIP OF GENETICS AND CLINICALLY SUSPECT ARTHRALGIA IN RA DEVELOPMENT ASSESSED USING HC, CSA AND RA PATIENTS
Authors: M. Maurits, F. Wouters, E. Niemantsverdriet, T. Huizinga, A. van der Helm - van Mil, R. Knevel
Journal: Annals of the Rheumatic Diseases (2021)

Background: The identification of a pre-RA stage of patients with clinically suspect arthralgia (CSA) has proven to be beneficial in the early detection of Rheumatoid disease. Similarly, genetic susceptibility studies have identified important genetic risk factors for the development of (CCP positive) RA. 1 The question that arises is whether these findings represent independent etiological pathways and could therefore be complimentary in the early diagnosis of RA. Objectives: To corroborate the knowledge of genetic differences between HC and RA patients and extend it to include the CSA stage of disease. Methods: We used three datasets sampled from the same region in the Netherlands: 1,085 healthy controls (HC), 530 CSA and 1,277 RA patients. CSA patients were monitored for a median of 2 years for conversion into clinically apparent inflammatory arthritis (CSAc) or not (CSAnc). 2 We assessed the association between HLA SE and disease stage using logistic regression. The analysis was repeated in the CCP positive and CCP negative strata of both the CSA and the RA populations. Results: Consistent with previous studies, HLA SE was significantly enriched in RA patients compared to HC (OR 2.28) (Figure 1). HLA SE also differentiated HC vs CSAc (OR 1.69), CSAnc vs CSAc (OR 1.74), and CSAnc vs RA (0R 2.35). No difference was found in HC vs CSAnc and CSAc vs RA. Conclusion: HLA SE is more prevalent in patients who developed (rheumatoid) arthritis than in both healthy controls and CSA patients who do not progress to arthritis. The results presented here seem to indicate a clear distinction between CSA patients who develop arthritis and those who do not. We therefore believe that known RA genetics play a role in the development of arthritis rather than the CSA symptoms. While this relationship varies by CCP status, an independent effect remains. Studies into the broader role of genetics beyond HLA SE are currently underway. Figure 1. Distinguishing ability of HLA SE across HC, CSAc, CSAnc and RA in the full populations as well as in the CCP positive and negative stratifications. The arrowhead indicates the “case” status in each logistic regression. OR’s (95% CI) derived from regression coefficients indicate the change in odds ratio attributable to HLA SE positivity. References: [1]van der Helm-van Mil, A. H., et al. Arthritis and rheumatism, 2006. 54(4): p. 1117–1121. [2]van Steenbergen, H.W., et al. Ann Rheum Dis, 2017. 76(3): p. 491-496. Disclosure of Interests: None declared
LSD1 and Aberrant DNA Methylation Mediate Persistence of Enteroendocrine Progenitors That Support <i>BRAF</i>-Mutant Colorectal Cancer
Authors: Samuel A. Miller, Robert A. Policastro, Shruthi Sriramkumar, Tim Lai, Thomas D. Huntington, Christopher A. Ladaika, Daeho Kim, Chunhai Hao, Gabriel E. Zentner, Heather M. O'Hagan
Journal: Cancer Research (2021)

Abstract Despite the connection of secretory cells, including goblet and enteroendocrine (EEC) cells, to distinct mucus-containing colorectal cancer histologic subtypes, their role in colorectal cancer progression has been underexplored. Here, our analysis of The Cancer Genome Atlas (TCGA) and single-cell RNA-sequencing data demonstrates that EEC progenitor cells are enriched in BRAF-mutant colorectal cancer patient tumors, cell lines, and patient-derived organoids. In BRAF-mutant colorectal cancer, EEC progenitors were blocked from differentiating further by DNA methylation and silencing of NEUROD1, a key gene required for differentiation of intermediate EECs. Mechanistically, secretory cells and the factors they secrete, such as trefoil factor 3, promoted colony formation and activation of cell survival pathways in the entire cell population. Lysine-specific demethylase 1 (LSD1) was identified as a critical regulator of secretory cell specification in vitro and in a colon orthotopic xenograft model, where LSD1 loss blocks formation of EEC progenitors and reduces tumor growth and metastasis. These findings reveal an important role for EEC progenitors in supporting colorectal cancer. Significance: This study establishes enteroendocrine progenitors as a targetable population that promotes BRAF-mutant colorectal cancer and can be blocked by LSD1 inhibition to suppress tumor growth.
Physical methods for enhancing drug absorption from the gastrointestinal tract
Authors: Zhi Luo, Nevena Paunović, Jean-Christophe Leroux
Journal: Advanced Drug Delivery Reviews (2021)

Overcoming the gastrointestinal (GI) barriers is a formidable challenge in the oral delivery of active macromolecules such as peptide- and protein- based drugs. In the past four decades, a plethora of formulation strategies ranging from permeation enhancers, nanosized carriers, and chemical modifications of the drug's structure has been investigated to increase the oral absorption of these macromolecular compounds. However, only limited successes have been achieved so far, with the bioavailability of marketed oral peptide drugs remaining generally very low. Recently, a few approaches that are based on physical interactions, such as magnetic, acoustic, and mechanical forces, have been explored in order to control and improve the drug permeability across the GI mucosa. Although in the early stages, some of these methods have shown great potential both in terms of improved bioavailability and spatiotemporal delivery of drugs. Here, we offer a concise, yet critical overview of these rather unconventional technologies with a particular focus on their potential and possible challenges for further clinical translation.
AB0232 PREVALENCE OF INFECTIONS UNDER BIOTHERAPY DURING RHEUMATOID ARTHRITIS
Authors: K. Baccouche, R. Grassa, S. Lataoui, O. Jomaa, N. El Amri, H. Zeglaoui, E. Bouajina
Journal: Annals of the Rheumatic Diseases (2021)

Background: Biologic therapies are emerging as a significant therapeutic option for many with debilitating inflammatory and autoimmune conditions including rheumatoid arthritis (RA).These biological agents are highly effective in RA. Potential complications are dominated by infections. Objectives: To evaluate the different infections occurred under biotherapy. Methods: This is a descriptive retrospective study including patients under biotherapy, hospitalized between 2000-2016 in the Rheumatology Department of Farhat Hached hospital in Sousse,Tunisia. We evaluated for each patient the different infections that have occurred, specifying the different types of biotherapy received. Results: Sixty one patients are included (54 women and 7 men).The average age is 55.33 years ±11.51 [34-81 years].We found 47 infections in 40 patients (65.57%) with at least one infection under biotherapy: 41 women and 6 men with a mean age at 57.72 years [34-81 years]. Infections occurred under anti IL6 in 46.32%, Infliximab in 31.58%, anti CD20 in 11.58%, Etanercept in 7.37% and under Certolizumab in 3.16%. The infection was bacterial in 68.42%: 28 pulmonary infections, 8 oto rhino laryngology infections, 14 urinary infections, 2 soft tissue abscess, 13 cutaneous infections, 02 ocular infections. A viral origin of the infection was noted in 12.63% of cases. As for mycosis infections they represent 18.75% of the etiologies identified. The treatment was medical in 100% of cases and the evolution was favorable in all patients without resorting to the definitive discontinuation of biotherapy. Conclusion: The infections reported in our series are much more frequent under anti IL6 treatment and bacteria are the most incriminating pathogenic agents in our patients. References: [1]Simon, T. A.,and al. Comparative risk of malignancies and infections in patients with rheumatoid arthritis initiating abatacept versus other biologics: a multi-database real-world study. Arthritis Research &amp; Therapy, 21(1).(2019). [2]Pawar, A.,and al Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study. Annals of the Rheumatic Diseases, annrheumdis–2018–214367(2019). Disclosure of Interests: None declared
Publisher Correction: Prevalence of monoclonal gammopathy of undetermined significance (MGUS) at HIV diagnosis in individuals 18–40 years old: a possible HIV indicator condition
Authors: Michele Bibas, Silvia Pittalis, Nicoletta Orchi, Gabriella De Carli, Chiara Agrati, Enrico Girardi, Andrea Antinori, Vincenzo Puro, Giuseppe Ippolito
Journal: Blood Cancer Journal (2021)
Increased Uptake of 18F-THK5351 in Glioblastoma But Not in Primary Central Nervous System Lymphoma
Authors: Katsuya Mitamura, Takashi Norikane, Yuka Yamamoto, Keisuke Miyake, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2021)

Abstract 18 F-THK5351 was initially developed to target tau aggregates in neurofibrillary tangles. However, it was also shown to bind to an enzyme, monoamine oxidase B, which is highly expressed in the outer mitochondrial membrane of astrocytes. In a case with glioblastoma, both l -[methyl- 11 C]-methionine PET and 18 F-THK5351 PET showed increased uptake in the tumor. On the other hand, in another case with primary central nervous system lymphoma, l -[methyl- 11 C]-methionine PET showed increased uptake in the tumor, but 18 F-THK5351 PET showed no abnormal uptake in the tumor. 18 F-THK5351 PET might be helpful in differentiating between glioblastoma and primary central nervous system lymphoma.
Telecommunicator Cardiopulmonary Resuscitation—A Strategy Whose Time Has Come for the Other Pandemic
Authors: Richard Chocron, Miranda Lewis, Thomas Rea
Journal: JAMA Network Open (2021)

The study by Sanko et al 1 demonstrates the potential of using telecommunicator CPR to improve early CPR in sudden cardiac arrest among 9-1-1 callers or bystanders with limited English proficiency and those with English proficiency.Like most relevant research, the study suggests important next steps for consideration by stakeholders committed to improving public health.
England urged to introduce minimum alcohol pricing
Authors: Bryan Christie
Journal: BMJ (2021)

Further evidence of the success of minimum unit pricing of alcohol in reducing consumption has led to renewed calls for the policy to be introduced in England.

Scotland was the first country in the European Union to introduce a minimum price of 50p per unit of alcohol in 2018, and Wales followed in March 2020. A research study led by the University of Newcastle has found that alcohol sales in both Scotland and Wales have fallen since the introduction of …
POS1018 IMPORTANCE OF LATERAL SPINE VIEW IN DXA BONE DENSITOMETRY IN PATIENTS WITH SPONDYLOARTHRITIS
Authors: S. Miri, H. Ferjani, K. Maatallah, A. Kasraoui, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Osteoporosis is an increasingly important health problem among patients with spondyloarthritis (SPA). The Measure of Bone Mineral Density BMD is routinely carried out in an anteroposterior (AP) view of the spine. However, the syndesmophytes, ligaments calcifications, and the posterior part of vertebrae affect AP scanning. A lateral spine view is a more sensitive tool in assessing bone loss in trabecular bone. Objectives: We aimed to evaluate the association between lateral lumbar DXA and syndesmophyte grading in patients with SPA. Methods: We conducted a retrospective study including 75 patients with SPA. Bone density of the hip and lumbar spine was measured with a GE Lunar Prodigy Advance Bone Densitometer equipment. All patients had lumbar lateral, AP, and proximal femur DXA scans. The T-score, which measures the difference between a patient’s BMD and young-normal subjects, was computed and age-matched. Results: The mean age of the patients was 36±11 years. Male predominance was noted with a sex ratio of 4.76. The mean BMI was 25±5 kg/m2. Eight percent were obese. Fifty-two percent had Vitamin D deficiency. Forty-eight percent of the patients had axial SPA, while 52% had axial and peripheral symptoms. The mean age of onset was 27±7 years. Fifty-two percent of the patients had high inflammatory biomarkers. The BASDAI, ASDAS-VS, and ASDAS-CRP mean levels were respectively: 3.5±2.4, 3.1±0.9, and 3±0.8. The mean BASRI and mass were respectively 8 + 4.8 and 16.4 + 19.4. Analyses of T-score values obtained over the femoral neck revealed osteoporosis in 18.7% of the cases and osteopenia in 32% of the cases. On the other hand, analyses of AP, spine views revealed osteoporosis in 25.3% and osteopenia in 45.3% of patients (p=0.028, r=0.254). We detected the highest percentage of osteoporosis in lateral lumbar view and T-scores matched more closely with femoral neck values; osteoporosis in 29.3%, and osteopenia in 22.7% of the patients (p&lt;10-3, r=0.562). BMD measured in AP, and lateral views were in good agreement (p&lt;10-3, p=0.592). Age was inversely but not significantly associated with BMD in lateral (p=0.442, r=-0.09), AP (p=0.319, r=-0.117) and femoral neck projections (p=0.179, r=-0.157). Femoral neck BMD was associated with the activity of SPA (ASDAS vs (p=0.027, r= -0.295), and the mobility limitation BASMI (p=0.032, r= -0.247). Coxitis, BASRI, or mSASS were independent of BMD. Conclusion: We conclude that spine lateral view in DXA accurately measures BMD exceeding the AP spine views and femoral neck values. Therefore, structural changes do not affect this measurement Disclosure of Interests: None declared.
AB0350 MATERNAL AND FETAL OUTCOME IN MEXICAN WOMEN WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME, SECONDARY ANTIPHOSPHOLIPID SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOSUS WITH ANTIPHOSPHOLIPID ANTIBODIES
Authors: A. A. Sánchez, D. Miranda, M. A. Saavedra, A. Sanchez Gonzalez, Z. Castro
Journal: Annals of the Rheumatic Diseases (2021)

Background: Primary antiphospholipid syndrome (APS) is associated with a higher frequency of maternal-fetal adverse outcomes, with increased risk when APS is associated with systemic lupus erythematosus (SLE). Objectives: We compared maternal-fetal complications in patients with primary APS, APS associated with SLE and SLE with anti-phospholipid antibodies (aPLs). Methods: Observational, analytical, retrospective, cross-sectional, comparative study, between 2009-2019. Three groups were compared: primary APS, APS associated with SLE and SLE with anti-phospholipid antibodies (aPLs). Results: We include 179 pregnant women, 31.8% with primary APS, 35.8% with APS associated with SLE, and 32.4% with SLE and aPLs A history of a higher frequency of abortions was found in APS associated with SLE (62.5%, p &lt;0.001) and thrombosis (61.9%, p &lt;0.001) and aCL IgG + in primary APS (80.7%, p = 0.011). More frequent use during pregnancy of antimalarials is applied in associated APS (81.30%, p &lt;0.001) and aspirin / heparin in primary APS (96.5% / 94.7%, p &lt;0.001). Abortions were observed more frequently in APS associated with SLE (23.80%, p = 0.021) and preeclampsia / HELLP in primary APS (31.6% and 15.8%, p = 0.047) who were also less frequently the use of antimalarial (24% vs. 81.3% vs. 72.4%, p &lt;0.001) compared to the other groups. Table 1 Conclusion: Patients with APS and SLE have an increased risk of miscarriage whereas those with primary APS have an increased risk for preeclampsia / HELLP. The use of antimalarials could reduce the risk of hypertensive disorders of pregnancy. References: [1]Schreiber K, Sciascia S, de Groot PG, et al. Antiphospholipid syndrome. Nat Rev Dis Primers 2018;4:17103. [2]De Carolis S, Tabacco S, Rizzo F, et al. Antiphospholipid syndrome: An update on risk factors for pregnancy outcome. Autoimmun Rev. 2018;17:956-66. Table 1. Comparison between groups of adverse maternal-fetal outcome. Secondary antiphospholipid syndrome (n=64 ) Primary antiphospholipid syndrome (n=57 ) Systemic lupus erythematosus with antiphospholipid antibodies (n=58 ) P Fetal complications 48 (76.20%) 43 (75.40%) 31 (56.40%) 0.034 Growth restriction 9 (14.30%) 8 (14%) 7 (12.50%) 0.955 Oligohydramnios 6 (9.50%) 5 (8.80%) 5 (8.90%) 0.989 Prematurity 23 (52.30%) 25 (56.80%) 19 (42.20%) 0.37 Abortion 15 (23.80%) 3 (5.40%) 9 (16.10%) 0.021 Stillbirth 7 (11.10%) 10 (17.90%) 5 (9.10%) 0.343 Low birth weight 20 (52.60%) 21 (48.80%) 15 (37.50%) 0.373 Malformations 5 (8.10%) 0 (0%) 0 (0%) 0.01 Maternal complications 40 (63.50%) 25 (43.90%) 21 (36.80%) 0.01 Pre-eclampsia. 15 (23.80%) 18 (31.60%) 7 (12.30%) 0.046 HELLP 4 (6.30%) 9 (15.8%) 2 (3.50%) 0.047 Premature rupture of membranas 7 (11.10%) 5 (8.8%) 4 (7.10%) 0.75 Maternal death 1 (1.60%) 0 (0%) 1 (1.80%) 0.616 Disclosure of Interests: None declared
Lower Extremity Peripheral Artery Disease Without Chronic Limb-Threatening Ischemia
Authors: Tamar S. Polonsky, Mary M. McDermott
Journal: JAMA (2021)

<h3>Importance</h3> Lower extremity peripheral artery disease (PAD) affects approximately 8.5 million people in the US and approximately 230 million worldwide. <h3>Observations</h3> Peripheral artery disease is uncommon before aged 50 years but affects up to 20% of people aged 80 years and older. It can be noninvasively diagnosed with the ankle-brachial index (ABI), a ratio of Doppler-recorded pressures in the dorsalis pedis and/or posterior tibial artery in each leg to brachial artery pressures. An ABI value less than 0.90 is 57% to 79% sensitive and 83% to 99% specific for arterial stenosis of at least 50%. Intermittent claudication, consisting of exertional calf pain that does not begin at rest and that resolves within 10 minutes of rest, is considered the classic symptom of PAD. However, 70% to 90% of people with an ABI value less than 0.90 either report no exertional leg symptoms (ie, asymptomatic) or report leg symptoms with walking that are not consistent with classic claudication. Over time, people with PAD restrict walking activity or slow walking speed to avoid leg symptoms. Thus, although approximately 75% of people with PAD report no change in leg symptoms over time, those with PAD have significantly greater annual declines in 6-minute walk performance compared with those without it. Approximately 11% of people with PAD develop chronic limb-threatening ischemia, the most severe form of PAD. Compared with people without PAD, those with the disease have approximately twice the rate of all-cause mortality, cardiovascular mortality, and major coronary events at 10-year follow-up. High-dose statins and antiplatelet therapy with or without antithrombotic therapy reduced rates of coronary events and stroke in people with PAD. Supervised treadmill exercise improved 6-minute walk distance by 30 to 35 m, consistent with a clinically meaningful change, whereas effective home-based walking exercise interventions improved 6-minute walk by 42 to 53 m. Effective home-based exercise programs require behavioral methods, including monitoring by a coach. <h3>Conclusions and Relevance</h3> Peripheral artery disease affects approximately 230 million people worldwide and is associated with increased rates of cardiovascular events, lower extremity events, and functional decline compared with that of people without PAD. People with PAD should be treated with the highest dose of statin tolerated, antithrombotic and/or antiplatelet therapy, and exercise.
POS1302 THE MUSCULOSKELETAL SYSTEM MANIFESTATIONS IN CHILDREN WITH FAMILIAL MEDITERRANEAN FEVER
Authors: F. Demir, S. Canbek, B. Sözeri
Journal: Annals of the Rheumatic Diseases (2021)

Background: Familial Mediterranean fever (FMF) is a monogenic inherited periodic fever syndrome presenting with episodes of self-limiting fever and inflammation of serosal membranes. The attacks emerge with arthritis were defined as one of the major diagnostic criteria besides involvement of serosal membranes. Non-specific musculoskeletal findings such as myalgia, arthralgia, transient synovitis, and more rare manifestations like protracted febrile myalgia can also be seen in FMF patients attacks Objectives: We aim to reveal the frequency and genotype association of musculoskeletal manifestations in children with FMF. Methods: The patients diagnosed with FMF between January 1, 2017 and June 1, 2019, and followed for at least 6 months in our pediatric rheumatology clinic were included in the study. Musculoskeletal manifestations of patients were enrolled. The patients were grouped according to the “Mediterranean Fever” (MEFV) gene variants. Musculoskeletal manifestations of the patients were compared between the groups Results: The study group included 634 children with FMF (336 female and 298 male, F/M: 1.13/1). The clinical manifestations of patients in attack period were as follows: 99% of the patients had fever, 87.3% had abdominal pain, 20.7% had chest pain, 11.3% had vomiting, 10.7% had erysipelas like erythema, and 9.3% had headache. The musculoskeletal symptoms were accompanied by 58.6% (n: 372) of the patients during the attack period. The most common musculoskeletal manifestation was found as arthralgia (32.6%, n: 206). Also, the other musculosceletal manifestations were found as follows during attacks; arthritis in 23.7% (n: 150), myalgia in 20.5% (n: 130), exertional calf pain in 6.5% (n: 41), and protracted febrile myalgia in 1% (n: 7) of the patients. It was observed that the musculoskeletal manifestations were significantly higher in patients with homozygous M694V variant in exon-10 (p=0.017). Also, it was found that the musculoskeletal manifestations are more common in the attack periods of patients carrying the M694V variant in at least one allele (p = 0.019). Conclusion: It was determined that the musculoskeletal manifestations were seen as an attack symptom in more than half of FMF patients. Also, homozygous and compound heterozygous MEFV mutations including M694V variant found as a risk factor for emerge of musculoskeletal manifestations. In children with unexplained and recurrent musculoskeletal symptoms, especially in ethnicities with the high frequency of FMF, analysis of MEFV gene can help reveal the underlying cause. References: [1]Brik R, Shinawi M, Kasinetz L, Gershoni-Baruch R. The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis Rheum 2001;44:1416-9. [2]Jarjour RA, Dodaki R. Arthritis patterns in familial Mediterranean fever patients and association with M694V mutation. Mol Biol Rep 2011;38:2033-6. Disclosure of Interests: None declared