tbuckley/cabot-search huggingface dataset:
Psychological Health, Well-Being, and the Mind-Heart-Body Connection: A Scientific Statement From the American Heart Association
Authors: Glenn N. Levine, Beth E. Cohen, Yvonne Commodore-Mensah, Julie Fleury, Jeff C. Huffman, Umair Khalid, Darwin R. Labarthe, Helen Lavretsky, Erin D. Michos, Erica S. Spatz, Laura D. Kubzansky
Journal: Circulation (2021)

As clinicians delivering health care, we are very good at treating disease but often not as good at treating the person. The focus of our attention has been on the specific physical condition rather than the patient as a whole. Less attention has been given to psychological health and how that can contribute to physical health and disease. However, there is now an increasing appreciation of how psychological health can contribute not only in a negative way to cardiovascular disease (CVD) but also in a positive way to better cardiovascular health and reduced cardiovascular risk. This American Heart Association scientific statement was commissioned to evaluate, synthesize, and summarize for the health care community knowledge to date on the relationship between psychological health and cardiovascular health and disease and to suggest simple steps to screen for, and ultimately improve, the psychological health of patients with and at risk for CVD. Based on current study data, the following statements can be made: There are good data showing clear associations between psychological health and CVD and risk; there is increasing evidence that psychological health may be causally linked to biological processes and behaviors that contribute to and cause CVD; the preponderance of data suggest that interventions to improve psychological health can have a beneficial impact on cardiovascular health; simple screening measures can be used by health care providers for patients with or at risk for CVD to assess psychological health status; and consideration of psychological health is advisable in the evaluation and management of patients with or at risk for CVD.
THU0122 Antioxidant vitamins and lipid peroxidation in patients with rheumatoid arthritis: association with inflammatory markers
Authors: S Paredes, J Girona, JC Vallvé, E Hurt-Camejo, M Heras, L Masana
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease that has been associated with an increase of cardiovascular disease (CVD). However, the mechanism underlying the high incidence of CVD is unclear. It has been postulated that the chronic inflammation associated with RA could lead to an accelerated atherogenesis. Lipid peroxidation and low antioxidants levels are associated with increase of CVD and RA. Furthermore, inflammatory markers and cytokines has related with inflammatory responses and pathogenesis in RA and also atherosclerosis. <h3>Objectives</h3> To evaluate in RA patients the vitaminic status and their relation with secretory phospholipase A2 (sPLA2) and other inflammatory markers, and also lipid peroxidation parameters. <h3>Methods</h3> The study comprises 30 patients with diagnosed RA according ACR 1987 criteria under treatment and 30 matched controls. Inflammatory markers studied were sPLA2, VCAM, ICAM, TNFα, IFNγ, CRP, ESR and fibrinogen. Lipid profile, size distribution of LDL subclasses and the binding affinity of LDL to chondroitin-6-sulfate glycosaminoglycan (GAG) were analysed. The vitamins A and E were determinated in plasma by HPLC. The susceptibility of LDL oxidation was evaluated by the kinetics of conjugated dienes formation induced by hemin. Lag phase (LP), maximal rate of diene production (MR), and maximum diene production (MDP) were studied. <h3>Results</h3> RA patients had significant higher plasma levels of sPLA2, VCAM, ICAM, TNFα, IFNγ, CRP, ESR and fibrinogen compared with controls. LDL cholesterol in patients with RA was lower (p &lt; 0.05). Plasma RA patients had significantly higher levels of small dense LDL and lower levels of large light LDL than controls (p &lt; 0.01). LDL affinity (Kd) to GAG were significantly higher in RA patients than in controls (p &lt; 0.05). No differences were observed in vitamins and among the different phases of the dienes formation. In RA patients, a negative correlation between vitamins A and E and sPLA2 (p &lt; 0.01), as well as between vitamins and CRP(p &lt; 0.01), was observed. A positive correlation between Kd LDL and LP (p &lt; 0.05) in RA patients was observed. <h3>Conclusion</h3> These results suggest that inflammation influences the vitaminic status in RA patients. This alteration combined with the presence of atherogenic small LDL with high affinity for GAG may contribute sinergistically to the higher risk for atherosclerotic CVD reported in RA patients.
SAT0170 Risedronate reduces the risk of new vertebral fractures in 1 year in postmenopausal women on corticosteroid therapy
Authors: RF Laan, C Benhamou, H Taggart, E Sod
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Five hundred and nine patients, receiving moderate to high doses of oral corticosteroids (equivalent to 7.5 mg prednisone daily or greater), were enrolled in two studies to examine the effect of risedronate. <h3>Objectives</h3> We report here on the results of the group of postmenopausal women in these studies (n = 255). <h3>Methods</h3> Patients in these studies were randomised to receive placebo, or risedronate (RIS) 2.5 mg, or RIS 5 mg for 1 year. Patients were supplemented with daily elemental calcium (500–1000 mg) and the majority also received supplemental vitamin D (400 IU). Spinal BMD was measured every 3 months; spinal radiographs were taken at baseline and 1 year. <h3>Results</h3> In this group of postmenopausal women, RIS 5 mg significantly increased spinal BMD by 2.6% vs placebo (p less than 0.01). Nine out of 56 placebo patients had a new vertebral fracture compared with 3 out of 62 in the RIS 5 mg treated group. This vertebral fracture risk reduction was 73% (p = 0.050). Effects of 2.5 mg were consistent with these results. <h3>Conclusion</h3> In summary, this study demonstrates that risedronate is effective in maintaining or increasing bone mass and reducing the risk of new vertebral fractures in postmenopausal women on corticosteroid therapy. These findings are consistent with risedronate effects observed in large, 3 year studies in women with confirmed postmenopausal osteoporosis.
Abstract 14397: Novel CYP2C19 Genetic Variants Associated With Stent Thrombosis - A Next Generation Sequencing Study
Authors: Lingxin Zhang, Joel A Morales-Rosado, Kashish Goel, Axel Akerblom, Saurabh Baheti, John Black, Niclas Eriksson, Lars C Wallentin, Stefan K James, Robert F Storey, Shaun G Goodman, Gregory Jenkins, Bruce Eckloff, Suzette J Bielinski, Hugues Sicotte, Stephen Johnson, Veronique L Roger, Liewei Wang, Richard Weinshilboum, Eric Klee, Charanjit Rihal, Naveen L Pereira
Journal: Circulation (2019)

Background: The objective of this study was to describe CYP2C19 sequencing results in the largest series of clopidogrel treated cases of stent thrombosis (ST), the closest clinical phenotype to gen...
OP0010 Neutralisation of il-18 activity is a disease-modifying therapy in the murine collagen-induced arthritis model
Authors: C Plater-Zyberk, LA Joosten, MA Helsen, P Sattonnet-Roche, C Siegfried, S Alouani, AJ Van de Loo, P Graber, E Lubberts, CA Dinarello, WB Van den Berg, Y Chvatcko
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Interleukin-18 (IL-18) is a member of the interleukin-1 cytokine family. <i>In vivo</i> IL-18 has been demonstrated as promoting the development of a TH1 response in synergy with IL-12. Patients with rheumatoid arthritis (RA) have in their joints significant levels of IL-18 and IL-12. <h3>Objectives</h3> This study was aimed at studying the effect of neutralising endogenous IL-18 <i>in vivo</i> in collagen-induced arthritic (CIA) mice, to define the therapeutic potentials of IL-18 blockade for the treatment of patients with RA. <h3>Methods</h3> Two distinct IL-18 neutralising strategies were used, i.e. a recombinant human IL-18 binding protein (rIL-18BP) and a polyclonal rabbit anti-mouse IL-18 IgG, to treat CIA mice in a therapeutic protocol (after disease onset). The effect on disease severity (visual scores) as well as parameters of cartilage and bone destruction were evaluated. <h3>Results</h3> Clinical scores were significantly reduced after IL-18 blockade (rhIL-18BP 1 mg/kg, p &lt; 0.001, n = 13; anti-IL18 IgG, 2 mg, p &lt; 0.05, n = 9, Mann Whitney test, treated versus placebo groups). Histological examination showed cartilage protection (decrease erosion scores, p &lt; 0.05) that was accompanied by significantly reduced levels of serum cartilage oligomeric matrix protein (an indicator of cartilage turnover) and VDIPEN expression (a neoepitope present after digestion by matrix metalloproteinases). X-ray analysis of joints provided evidence of reduced bone erosion. <h3>Conclusion</h3> These results clearly demonstrate that neutralising endogenous IL-18 is therapeutically efficacious in the CIA model and support the use of IL-18 neutralisation as a novel cartilage and bone sparing therapy for the treatment of destructive arthritis. Recombinant hIL-18BP could therefore represent a new disease-modifying anti-rheumatic drug that warrants testing in clinical trials in patients with rheumatoid arthritis.
Political economy of covid-19: extractive, regressive, competitive
Authors: Jesse B Bump, Fran Baum, Milin Sakornsin, Robert Yates, Karen Hofman
Journal: BMJ (2021)

19 reflects longstanding patterns of resource extraction linked to racial discrimination, marginalisation, and colonialism, write Jesse Bump and colleagues• Progress in public health requires governance reforms at multilateral institutions and international redistribution mechanisms
THU0102 Apo(a), a potential link between atherosclerosis and arthritis
Authors: N Busso, J Dudler, R Salvi, V Péclat, R Darioli, P Nicod, A So, V Mooser
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Patients with rheumatic diseases have an excess in cardiovascular morbidity and mortality, suggesting the presence of common pathogenic abnormalities for both atherosclerosis and arthritis. One particularly atherogenic apolipoprotein, apo (a), an homologue of plasminogen, may be involved by competing with plasminogen for fibrin binding and by interfering with fibrinolysis. <h3>Objectives</h3> To study the expression of apo (a) in arthritic joints. <h3>Methods</h3> Human studies: synovial fluid and plasma from patients with osteoarthritis (OA, n = 8), rheumatoid arthritis (RA, n = 12) and other types of inflammatory arthritis (n = 12) and synovial tissues from OA and RA patients were collected. Apo (a) was quantitated by ELISA and in tissues also by RNase protection. Moreover, immunohistochemical analyses of apo (a) and fibrin were performed on synovial tissues. Animal studies: antigen-induced arthritis (AIA) was induced in genetically modified mice (LDL-receptor deficient (LDL-R -/-) mice expressing a human apoB-100 transgene (hApoB +/+) and a human apo (a) transgene (apo (a) ±)). Joint inflammation was assessed by technetium scintigraphy and histology. <h3>Results</h3> We detected the presence of apo (a) as a full-length glycoprotein in human arthritic joints. The amount of apo (a) in synovial fluid rose in proportion to plasma apo (a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo (a) immunoreactive material, but not apo (a) transcripts, was detected in arthritic synovial tissues. This data indicated that synovial fluid apo (a) originates from the circulation and that diffusion through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo (a) colocalized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human apo (a). In this particular mouse model, the presence of apo (a) did not change joint inflammation. <h3>Conclusion</h3> Even if the presence of apo (a) did not change the severity of AIA, we speculate that when levels of apo (a) are sufficiently high to inhibit fibrinolysis in the joints, apo (a) may exacerbate in humans the severity of the disease.
Cross-sectional adherence with the multitarget stool DNA test for colorectal cancer screening in a large, national study of insured patients.
Authors: Lesley-Ann Miller-Wilson, Lila J Finney Rutten, Jack Van Thomme, Burak Ozbay, Paul J. Limburg
Journal: Journal of Clinical Oncology (2021)

27 Background: Colorectal cancer (CRC) is the second most deadly and fourth most frequently diagnosed cancer in the United States. Early detection can improve CRC outcomes, but overall screening rates (62%) remain below the 80% goal set by the National Colorectal Cancer Roundtable. Multiple options are endorsed for average-risk CRC screening, including the multi-target stool DNA (mt-sDNA) test, which includes patient and provider navigation support. Cross-sectional adherence with the mt-sDNA test was previously reported in a large Medicare population (71%). In the current study we investigated cross-sectional adherence with the mt-sDNA test in a broader, national sample of insured patients. Methods: Aggregate data from Exact Sciences Laboratories LLC (ESL; Madison, WI) were retrospectively analyzed in compliance with HIPAA requirements. Study participants included individuals ages 50 years and older who were covered by commercial insurance or Medicare, had a valid mt-sDNA test order placed between January 1–December 31, 2018, and received a test kit shipped from ESL. Cross-sectional adherence, defined as successful completion and return of the test kit within 365 days of the shipment date, was assessed overall and by patient- and provider-level factors. Results: In total, 1,420,460 participants met the study criteria (61.2% women; mean age 65.7 years). Overall cross-sectional adherence was 66.8%. Adherence was 72.1% in participants with Traditional Medicare, 69.1% in participants with Medicare Advantage, and 61.9% in participants with commercial insurance (p&lt;0.001). Adherence increased by participant age (p&lt;0.001): 60.8% for ages 50-64, 71.3% for ages 65-75, and 74.7% for ages 76+ years. For Traditional Medicare patients, ages 65-75, adherence was 73.6%. Participants with mt-sDNA tests ordered placed by gastroenterologists had a higher adherence rate (78.3%) than those with orders placed by primary care clinicians (67.2%) (p&lt;0.001). Adherence rates were highest among patients with ordering providers in the Pacific region (71.4%) and West North Central region (70.1%), and lowest in the Mid-Atlantic region (65.7%), New England (65.2%), West South Central region (64.6%), and Puerto Rico and US territories (60.7%). Conclusions: Novel data from this large, national sample of insured patients demonstrate high cross-sectional adherence with the mt-sDNA test (66.8%), supporting the substantial contribution this guideline-endorsed option plays in average-risk CRC screening. At the patient-level, adherence increased with patient age, and was highest in those covered by Traditional Medicare. Provider-level stratification showed the highest adherence for mt-sDNA tests ordered by gastroenterologists. This study adds to data regarding the impact of accompanying navigation support and at-home convenience of mt-sDNA on screening completion rates.
FRI0247 Shoulder’s adhesive capsulitis. treatment by suprascapular nerve block
Authors: R Ghozlan, M Dupuis, C Lecarpentier, D Safa
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A new approach for the management of frozen shoulder associated with adhesive capsulitis is presented. <h3>Objectives</h3> The choice of blockade of the suprascapular nerve is a new concept for the management of the frozen shoulder. This is based on the fact that the nerve contains a high proportion of sensitive fibres supplying the shoulder joint. <h3>Methods</h3> 11 patients with adhesive capsulitis have been referred to us: women 9, men 2; mean age 55,5 years; mean duration of the disease 7,2 months. All the patients had failed to prior treatment. A suprascapular nerve block with anaesthesic solution and corticosteroid injection was performed by needle insertion through the suprascapular notch: behind the lateral end of the clavicle at its junction with the insertion of the trapezius muscle. <h3>Results</h3> Evaluation of the efficacy was achieved by comparing subjective pain and passive range of movement before and after the first block and after the final one. The block was repeated once weekly with a mean of 3 treatments. Relief of the pain has been noted in 8 of 11 patients. <h3>Conclusion</h3> This approach seems a new, non invasive and painless treatment of the adhesive capsulitis of the shoulder.
THU0248 Familial clustering of systemic lupus erythematosus with other autoimmune diseases
Authors: R Priori, F Conti, E Cassarà, E Medda, MA Stazi, R Gerli, A Manfredi, F Franceschini, MG Danieli, G Valesini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Previous studies have shown the phenomenon of clustering of autoimmune diseases (AD) in families of patients with Systemic Lupus Erythematosus (SLE). <h3>Objectives</h3> The purpose of this study was to evaluate the incidence, prevalence and risk to have an AD in first degree relatives (FDR) of patients with SLE and to investigate if a history of AD in FDR is a risk factor for SLE. <h3>Methods</h3> A multicentre case-control study was carried out in Italy. Cases and controls were randomly selected and interviewed using a detailed questionnaire. We conducted stratified analyses according to sex of relatives and/or proband to evaluate whether the relation between SLE in FDR and AD differs by sex. We used the extended generalised estimating equations (EGEE) to measure familial aggregation. The strenght of the association between family history of AD and SLE was measured as an odds ratio (OR). The adjusted OR was obtained by unconditional logistic regression model and the potentially confounding covariates were family size, age and sex of proband. <h3>Results</h3> The prevalence of AD among SLE and control FDR was respectively 6.1% and 1.5% (p &lt; 0.01). The incidence rate of AD and control FDR was 1.35 × 1000 py and 0.32 × 1000 py respectively. The relatives of SLE cases have 4 time probability of having AD compare to relatives of control (RR 4.26; 95% CI 2.25- 8.03). Using EGEE the adjusted OR taking into account the non-independence of family members was 4.77 (95 CI 2.07–11). A risk of 8.57 (95% CI 3.18–23.1) was detected if the proband is female and 1.40 (95% CI 0.22–8,78) if proband is male. The risk of AD is significantly greater for female with a female FDR with SLE (OR 10.36; 95% CI 2.90- 36.9). No AD was found among SLE spouses, while one case was found among spouses of controls. <h3>Conclusion</h3> This case-control study defines the risk to have an autoimmune disorder for SLE first degree relatives. A family history for AD represents a risk factor for SLE.
Phase II study of modulation of sorafenib (SOR)-induced autophagy using hydroxychloroquine (HCQ) in advanced hepatocellular cancer (HCC): Planned interim efficacy and safety analysis.
Authors: Sukeshi Patel Arora, Jennifer L. Moseley, Laura LaNiel Tenner, Luisa Arellano, Mary Salazar, Qianqian Liu, Joel Michalek, Devalingam Mahalingam
Journal: Journal of Clinical Oncology (2021)

305 Background: SOR is the first systemic therapy approved for advanced HCC, but has shown only modest improvements in survival. Resistance to SOR in pre-clinical models has been attributed to autophagy induction. Autophagy inhibition with HCQ enhanced SOR-induced cell death and apoptosis in early pre-clinic and clinical studies. Data from the phase I study of SOR plus HCQ in advanced solid tumors at showed clinical safety and efficacy. Therefore, we conducted a prospective study to evaluate efficacy of SOR and HCQ in advanced HCC patients (pts) (NCT03037437) and report planned interim analysis for our first-line cohort. Methods: Prospective phase II study of SOR 400 mg po BID + HCQ 400 mg daily in pts with advanced HCC (CP A-B8 cirrhosis). Cohort 1: first-line SOR/HCQ. Cohort 2: add HCQ upon progressing on SOR. CP B pts started at 200 mg BID, with dose escalation as tolerated. Cycle = 4 weeks. Primary endpoint: mTTP. Secondary endpoints: mOS, response by RECIST; AEs (NCI-CTCAEv3.0); PD analysis for markers of autophagy and immunity. Pts evaluable for efficacy if completed C1. Planned interim efficacy and safety analysis approved by DSMB is reported here. Results: For cohort 1, n = 19. Median age 63.5 (51-80). 80% Male; 65% Hispanics. ECOG 0-1: 100%. CP B cirrhosis: 32%. Etiology of cirrhosis: HCV 84%, ETOH 26%, NASH 5%. BCLC B 21%, C 70%. AFP &gt; 400: 47%, PVT: 32%, metastases: 64%, post-transplant: 21%. Reason off study: PD (n = 10), toxicity (n = 2), lost to f/u (n = 1), withdrew (n = 1). N = 16 completed C1, n = 2 remain on study. mTTP is 4.2 months (95% CI: 3.7-NA). mOS 13.8 months (95% CI: 13.8-NA). Response Rate (CR+PR): 25%. Best response: CR n = 1 (6%), PR n = 3 (19%), SD n = 7 (44%). 4+ cycles: n = 9 (56%). % alive. Median duration of response 7.6 months (3.67-20). Gr 1/2 AEs as expected from SOR. Gr 3: AST elevated (n = 1), diarrhea (n = 1) due to SOR. Gr 2 rash (n = 1) due to HCQ. No Gr 4/5. Dose reduction: 70% for SOR, 0% for HCQ. PD analysis on the 3 responders show favorable immune profile changes (increase in cytotoxic T cells and decrease T Regs). Conclusions: SOR/HCQ had a better response rate (25%) than historically SOR alone (2%) in pts with advanced HCC, predominantly BCLC C, with CP A and B cirrhosis. While immune checkpoint inhibitors (ICIs) are taking the forefront in advanced HCC, SOR/HCQ may have a role in patients with CP B cirrhosis, transplant or contraindications to ICIs. Further, analysis of predictive markers of response is ongoing. Clinical trial information: NCT03037437.
Oligodendrocyte precursor cell specification is regulated by bidirectional neural progenitor–endothelial cell crosstalk
Authors: Isidora Paredes, José Ricardo Vieira, Bhavin Shah, Carla F. Ramunno, Julia Dyckow, Heike Adler, Melanie Richter, Geza Schermann, Evangelia Giannakouri, Lucas Schirmer, Hellmut G. Augustin, Carmen Ruiz de Almodóvar
Journal: Nature Neuroscience (2021)