tbuckley/cabot-search huggingface dataset:
A multiple risk factor program is associated with decreased risk of cardiovascular disease in 70-year-olds: A cohort study from Sweden
Authors: Anna Nordström, Jonathan Bergman, Sabine Björk, Bo Carlberg, Jonas Johansson, Andreas Hult, Peter Nordström
Journal: PLoS Medicine (2020)

Background In individuals below 65 years of age, primary prevention programs have not been successful in reducing the risk of cardiovascular disease (CVD) and death. However, no large study to our knowledge has previously evaluated the effects of prevention programs in individuals aged 65 years or older. The present cohort study evaluated the risk of CVD in a primary prevention program for community-dwelling 70-year-olds. Method and findings In 2012–2017, we included 3,613 community-dwelling 70-year-olds living in Umeå, in the north of Sweden, in a health survey and multidimensional prevention program (the Healthy Ageing Initiative [HAI]). Classic risk factors for CVD were evaluated, such as blood pressure, lipid levels, obesity, and physical inactivity. In the current analysis, each HAI participant was propensity-score-matched to 4 controls (n = 14,452) from the general Swedish population using national databases. The matching variables included age, sex, diagnoses, medication use, and socioeconomic factors. The primary outcome was the composite of myocardial infarction, angina pectoris, and stroke. The 18,065 participants and controls were followed for a mean of 2.5 (range 0–6) years. The primary outcome occurred in 128 (3.5%) HAI participants and 636 (4.4%) controls (hazard ratio [HR] 0.80, 95% CI 0.66–0.97, p = 0.026). In HAI participants, high baseline levels of blood pressure and lipids were associated with subsequent initiation of antihypertensive and lipid-lowering therapy, respectively, as well as with decreases in blood pressure and lipids during follow-up. In an intention-to-treat approach, the risk of the primary outcome was lower when comparing all 70-year-olds in Umeå, regardless of participation in HAI, to 70-year-olds in the rest of Sweden for the first 6 years of the HAI project (HR 0.87, 95% CI 0.77–0.97, p = 0.014). In contrast, the risk was similar in the 6-year period before the project started (HR 1.04, 95% CI 0.93–1.17, p = 0.03 for interaction). Limitations of the study include the observational design and that changes in blood pressure and lipid levels likely were influenced by regression towards the mean. Conclusions In this study, a primary prevention program was associated with a lower risk of CVD in community-dwelling 70-year-olds. With the limitation of this being an observational study, the associations may partly be explained by improved control of classic risk factors for CVD with the program.
The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study
Authors: Rianne M. Douwes, António W. Gomes-Neto, Michele F. Eisenga, Elisabet Van Loon, Joëlle C. Schutten, Rijk O. B. Gans, Maarten Naesens, Else van den Berg, Ben Sprangers, Stefan P. Berger, Gerjan Navis, Hans Blokzijl, Björn Meijers, Stephan J. L. Bakker, Dirk Kuypers
Journal: PLoS Medicine (2020)

Background Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. Methods and findings We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7–9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38–2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21–2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48–3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23–2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation. Conclusions We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs. Trial registration ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.
Primary CNS Lymphomas (PCNSL) Patient-Derived Xenograft (PDX) Models Capture the Biological and Molecular Characteristics of the Disease
Authors: Frederic Pouzoulet, Agusti Alentorn, Mailys Daniau, Karima Mokhtari, Magali Le Garff-Tavernier, Frederic Davi, Matthieu Peyre, Franck Assayag, Dalila Labiod, Khe Hoang-xuan, Carole Soussain
Journal: Blood (2017)
SAT0336 SYMPTOMS OF AUTONOMIC DYSFUNCTION IN PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: P. Ostojic, M. Atanaskovic, M. Vujovic, M. Perovic
Journal: Annals of the Rheumatic Diseases (2020)

Objectives: This study aims to assess prevalence, severity and clinical correlates of symptoms of autonomic dysfunction in patients with SSc Methods: Fifty five consecutively recruited SSc patients were included in this study. Thirty seven (67.3%) patients had limited (lcSSc), whilst 18 (32.7%) patients had diffuse cutaneous SSc (dcSSc). Anticentromere antibodies (ACA) were positive in 31 (56.4%) of patients, whilst 20 (26.4%) patients had anti-topoisomerase I antibodies (ATA). All patients completed the Composite Autonomic Symptom Score (COMPASS-31) questionnaire, which consists of 31 items, quantifying six autonomic domains: orthostatic intolerance (OI), vasomotor (VD), secretomotor (SD), gastrointestinal (GD), bladder (BD) and pupillomotor dysfunction (PD). The total score ranges from 0 to 100, whilst scores for particular domains range as follows: 0-40 for OI, 0-5 for VD, 0-15 for SD, 0-25 for GD, 0-10 BD, and 0-5 for PD. Higher values representing more severe symptoms. Differences in total COMPASS-31 score and domain-specific scores were assessed with respect to disease form, antibody status, capillaroscopic findings, lung diffusing capacity and joint involvement. Moreover, we assessed the correlation between COMPASS-31 scores, disease status (assesed using the Scleroderma Assessment Questionnaire – SAQ) and severity of gastrointestinal symptoms (assessed using the UCLA SCTC GIT 2.0 questionnaire) Results: Percentage of SSc with a score &gt;0 in particular domains of the COMPASS-31 were as follows: OI – 32/55 (58.2%), VD – 49/55 (89.1%), SD – 36/55 (65.5%), GD – 40/55 (72.7%), BD - 26/55 (47.3%), PD – 30/55 (54.5%). The COMAPSS-31 score did not correlate with age or disease duration. There was no relationship between the COMPASS-31 total or subdomain scores and SSc subtype or autoantibody status. Similar mean values for total and subdomain scores were found among patients with different capillaroscopic patterns. Patients with DLCO &lt; 80% had significantly higher mean values of GD, BD and PD scores, compared to patients with DLCO≥80% (4.42 vs 2.75, 1.51 vs 0.38, 1.93 vs 1.09, respectively). Moreover, the total COMAPSS-31 score was significantly higher in patients with decreased DLCO (16.24 vs 11.34, p=0.008). Patients with joint involvement had higher COMPASS-31 score than patients without (17.74 vs 9.85, p=0.012). We have found a statistically significant (p&lt;0.001) correlation between the COMPASS-31 score and the Index of disease status (IDS), as well as the the total UCLA SCTC GIT score (rho=+0.45, rho=+0.51, respectively). Conclusion: Symptoms of dysautonomia are common in SSc patients. Patients with a more severe disease, especially decreased lung diffusing capacity, joint pain, and severe gastrointestinal involvement, report more symptoms of autonomic dysfunction. Disclosure of Interests: None declared
AB0701 ANTERIOR UVEITIS AND HLA B27, ARE THERE ANY CLINICAL OR THERAPEUTIC DIFFERENCES IN PATIENTS WITH POSITIVE HLA B27 VERSUS THOSE WITH HLA B27 NEGATIVE?
Authors: L. Lojo, B. Sánchez Marugán, C. Plasencia, L. Cebrian, M. A. Matias de la Mano, E. Calvo Aranda, M. T. Navío Marco
Journal: Annals of the Rheumatic Diseases (2020)

Background: Anterior uveitis is the most frequent form of presentation of uveitis. An important part of patients do not associate extraocular manifestations, so more information about the clinical profile is needed to optimize therapeutic decisions. Objectives: To describe the clinical profile of patients with anterior uveitis related and not related to the antigen HLA-B27. Compare both groups to establish differences. Methods: Retrospective cohort study. Consecutive patients diagnosed with non-infectious anterior uveitis, assessed in the multidisciplinary uveitis unit of the Infanta Leonor University Hospital (Madrid) from its establishment in October 2017 to December 2019, were included. To compare categorical variables Chi square was used and the test of Fisher; and Student’s T or Mann-Whitney U test for continuous variables. Finally, a multivariate analysis was performed to established differences between the two groups. A value of p &lt;0.05 was considered statistically significant. Results: 62 patients with anterior uveitis, 26 (42%) with HLA B27 positive and 36 (58%) with HLA B27 negative were included. There were no differences between the two groups regarding sex. Differences were found in the mean age at diagnosis, 35 + -9.6 in the HLA B27 positive group vs 47 + -14.9 in the HLA B27 negative group (p 0.01). The time since uveítis diagnosis was longer in the HLA B27 positive group: 7.08 years (3.45-11.79) versus 2.41 years (1.66-3) in the HLA B27 negative group (p 0.000). Regarding the etiology, the majority of patients in the HLA B27 negative group had a diagnosis of idiopathic anterior uveitis (72.2%), and 53.8% of the patients in the HLA B27 positive group were diagnosed with spondyloarthritis (p 0.000). There were no significant differences in the number of patients that require systemic treatment. There were no differences regarding oral corticosteroids intake, with very few patients needing it (2 patients in the HLA B27 positive group and 5 patients in the HLA B27 negative group (p 0.699). The percentage of patients who needed to start an immunosuppressive treatment were similar between the two groups, 6 patients (23.1%) in the HLA B27 positive group and 11 patients (30.6%) in the HLA B27 negative group (p 0.717) No significant differences could be detected between groups in the multivariate analysis in terms of laterality, clinical course, treatment with immunosuppressants or development of complications. Conclusion: In our cohort patients with HLA B27 positive debut at an earlier age. There were no differences between both groups in laterality, course of uveitis, systemic treatment or ocular complications. Disclosure of Interests: None declared
Association Between Healthy Eating Patterns and Risk of Cardiovascular Disease
Authors: Zhilei Shan, Yanping Li, Megu Y. Baden, Shilpa N. Bhupathiraju, Dong D. Wang, Qi Sun, Kathryn M. Rexrode, Eric B. Rimm, Lu Qi, Walter C. Willett, JoAnn E. Manson, Qibin Qi, Frank B. Hu
Journal: JAMA Internal Medicine (2020)

The 2015-2020 Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of cardiovascular disease (CVD).To examine the associations of dietary scores for 4 healthy eating patterns with risk of incident CVD.Prospective cohort study of initially healthy women from the Nurses' Health Study (NHS) (1984-2016) and the NHS II (1991-2017) and men from the Health Professionals Follow-up Study (HPFS) (1986-2012). The dates of analysis were July 25 to December 4, 2019.Healthy Eating Index-2015 (HEI-2015), Alternate Mediterranean Diet Score (AMED), Healthful Plant-Based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI).Cardiovascular disease events, including fatal and nonfatal coronary heart disease (CHD) and stroke.The final study sample included 74 930 women in the NHS (mean [SD] baseline age, 50.2 [7.2] years), 90 864 women in the NHS II (mean [SD] baseline age, 36.1 [4.7] years), and 43 339 men in the HPFS (mean [SD] baseline age, 53.2 [9.6] years). During a total of 5 257 190 person-years of follow-up, 23 366 incident CVD cases were documented (18 092 CHD and 5687 stroke) (some individuals were diagnosed as having both CHD and stroke). Comparing the highest with the lowest quintiles, the pooled multivariable-adjusted hazard ratios (HRs) of CVD were 0.83 (95% CI, 0.79-0.86) for the HEI-2015, 0.83 (95% CI, 0.79-0.86) for the AMED, 0.86 (95% CI, 0.82-0.89) for the HPDI, and 0.79 (95% CI, 0.75-0.82) for the AHEI (P for trend <.001 for all). In addition, a 25-percentile higher dietary score was associated with 10% to 20% lower risk of CVD (pooled HR, 0.80 [95% CI, 0.77-0.83] for the HEI-2015; 0.90 [95% CI, 0.87-0.92] for the AMED; 0.86 [95% CI, 0.82-0.89] for the HPDI; and 0.81 [95% CI, 0.78-0.84] for the AHEI). These dietary scores were statistically significantly associated with lower risk of both CHD and stroke. In analyses stratified by race/ethnicity and other potential risk factors for CVD, the inverse associations between these scores and risk of CVD were consistent in most subgroups.In 3 large prospective cohorts with up to 32 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of CVD. These findings support the recommendations of the 2015-2020 Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.
Annals Consult Guys - Should We Elect to Replace a 93-Year-Old's Hip?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2020)

Web Exclusives16 June 2020Annals Consult Guys - Should We Elect to Replace a 93-Year-Old's Hip?FREEGeno J. Merli, MD, Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author, Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article and Disclosure Informationhttps://doi.org/10.7326/W19-0039 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Gerardo MaradiagaHalifax Medical specialists30 June 2020 Thank you You always clarify multiple issues about patient care and I am very thankful for what you do.I am looking forward for the next issue. Author, Article and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, and Howard H. Weitz, MD, report that they have no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Eliseo Guallar, MD, MPH, DrPH, Deputy Editor, Statistics, reports that he has no financial relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 June 2020Volume 172, Issue 12Page: CG1KeywordsDiagnostic techniquesDisclosureHip ePublished: 16 June 2020 Issue Published: 16 June 2020 CopyrightCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
H. pylori infection alters repair of DNA double-strand breaks via SNHG17
Authors: Taotao Han, Xiaohui Jing, Jiayu Bao, Lianmei Zhao, Aidong Zhang, Renling Miao, Hui Guo, Baoguo Zhou, Shang Zhang, Jiazeng Sun, Juan Shi
Journal: Journal of Clinical Investigation (2020)

Chronic infections can lead to carcinogenesis through inflammation-related mechanisms. Chronic infection of the human gastric mucosa with Helicobacter pylori is a well-known risk factor for gastric cancer. However, the mechanisms underlying H. pylori–induced gastric carcinogenesis are incompletely defined. We aimed to screen and clarify the functions of long noncoding RNAs (lncRNAs) that are differentially expressed in H. pylori–related gastric cancer. We found that lncRNA SNHG17 was upregulated by H. pylori infection and markedly increased the levels of double-strand breaks (DSBs). SNHG17 overexpression correlated with poor overall survival in patients with gastric cancer. The recruitment of NONO by overabundant nuclear SNHG17, along with the role of cytoplasmic SNHG17 as a decoy for miR-3909, which regulates Rad51 expression, shifted the DSB repair balance from homologous recombination toward nonhomologous end joining. Notably, during chronic H. pylori infection, SNHG17 knockdown inhibited chromosomal aberrations. Our findings suggest that spatially independent deregulation of the SNHG17/NONO and SNHG17/miR-3909/RING1/Rad51 pathways upon H. pylori infection promotes tumorigenesis in gastric cancer by altering the DNA repair system, which is critical for the maintenance of genomic stability. Upregulation of SNHG17 by H. pylori infection might be an undefined link between cancer and inflammation.
Disease and healthcare burden of COVID-19 in the United States
Authors: Ian F. Miller, Alexander D. Becker, Bryan T. Grenfell, C. Jessica E. Metcalf
Journal: Nature Medicine (2020)

As of 24 April 2020, the SARS-CoV-2 epidemic has resulted in over 830,000 confirmed infections in the United States1. The incidence of COVID-19, the disease associated with this new coronavirus, continues to rise. The epidemic threatens to overwhelm healthcare systems, and identifying those regions where the disease burden is likely to be high relative to the rest of the country is critical for enabling prudent and effective distribution of emergency medical care and public health resources. Globally, the risk of severe outcomes associated with COVID-19 has consistently been observed to increase with age2,3. We used age-specific mortality patterns in tandem with demographic data to map projections of the cumulative case burden of COVID-19 and the subsequent burden on healthcare resources. The analysis was performed at the county level across the United States, assuming a scenario in which 20% of the population of each county acquires infection. We identified counties that will probably be consistently, heavily affected relative to the rest of the country across a range of assumptions about transmission patterns, such as the basic reproductive rate, contact patterns and the efficacy of quarantine. We observed a general pattern that per capita disease burden and relative healthcare system demand may be highest away from major population centers. These findings highlight the importance of ensuring equitable and adequate allocation of medical care and public health resources to communities outside of major urban areas. Projection of the number of COVID-19 cases and the associated burden on healthcare resources using a modified SEIR model reveals that rural regions in the United States are at risk of higher per capita case burdens, which could lead to health systems being overwhelmed in these areas.
Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial
Authors: David Z I Cherney, Claire C J Dekkers, Sean J Barbour, Daniel Cattran, Abdul Halim Abdul Gafor, Peter J Greasley, Gozewijn D Laverman, Soo Kun Lim, Gian Luca Di Tanna, Heather N Reich, Marc G Vervloet, Muh Geot Wong, Ron T Gansevoort, Hiddo J L Heerspink
Journal: The Lancet Diabetes & Endocrinology (2020)
Abstract IA12: Metabolic barriers to effective immunotherapy of cancer
Authors: Greg M. Delgoffe
Journal: Clinical Cancer Research (2020)

Abstract The tumor microenvironment presents a number of barriers to antitumor immunity, both immunologic and nonimmunologic in nature. It is now appreciated that, driven by the deregulated energetics of the cancer cells, the tumor microenvironment possesses a distinct metabolic landscape that may be detrimental to immune function, thus acting as a resistance mechanism to immunotherapy. I will discuss the metabolic defects present in tumor-infiltrating T cells and highlight the mechanistic underpinnings that drive these deficiencies. Further, I will discuss how genetic engineering, pharmacologic intervention, and costimulatory immunotherapy can be employed to modulate the metabolism of infiltrating T cells. Finally, I will describe how profiling the metabolism of patient tumor cells can yield insight into the regulation of immunity and the response to immunotherapy. Citation Format: Greg M. Delgoffe. Metabolic barriers to effective immunotherapy of cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA12.