tbuckley/cabot-search huggingface dataset:
PS1149 SECOND CANCER INCIDENCE IN CLL PATIENTS RECEIVING BTK INHIBITORS
Authors: D. Bond, Y. Huang, J. Fisher, A. Ruppert, D. Owen, E. Bertino, K. Rogers, S. Bhat, S. Jaglowski, M. Grever, J. Byrd, K. Maddocks, J. Woyach
Journal: HemaSphere (2019)

Background: Patients (pts) with chronic lymphocytic leukemia (CLL) suffer morbidity and mortality from CLL and increased risk for second primary neoplasia (SPN). BTK inhibitors (BTKi) are highly effective for the treatment of CLL and are associated with partial restoration of immune function with ongoing treatment. The impact of BTKi on the risk for and patterns of SPN is yet to be characterized. Aims: We aimed to determine the incidence of SPN including NMSC in a cohort of CLL pts treated with either ibrutinib or acalabrutinib at a single center, assess for association between baseline clinical characteristics and SPN incidence, and compare the observed with the expected incidence for sex and age matched controls within the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: CLL pts treated with ibrutinib or acalabrutinib at our center were identified retrospectively. Baseline and outcome data were collected including incidence of Richter's transformation (RT), non‐melanoma skin cancer (NMSC), and SPN. Standard incidence ratio (SIR) with 95% confidence intervals (CI) were calculated using expected incidence rates from the SEER, assuming a Poisson distribution for the observed incidence. Cumulative incidence rate (CIR) of SPN (excluding RT and NMSC) was calculated from BTKi start date to the diagnosis of SPN; death was a competing risk and pts without event were censored at last follow‐up. SPN was correlated with baseline data using the Fine‐Gray model. Results: 691 pts were included; the median age was 64 years, median prior lines of treatment was 2 (20% treatment‐naïve, 66% with prior chemo‐immunotherapy), and 56% were never smokers. At a median follow‐up of 44 months, 68 pts (10%) were diagnosed with SPN (SIR 2.4, CI 1.9–3.0) including 13 lung (SIR 3.2, CI 1.7–5.5), 9 melanoma (SIR 6.9, CI 3.1–13), 9 prostate (SIR 1.4, CI 0.6–2.6), 7 bladder (SIR 5.2, CI 2.1–10.6), 4 breast (SIR 1.7, CI 0.5–4.5), and 3 kidney cancers (SIR 2.9, CI 0.6–8.5). CIR of SPN at 3 year was 7.6% (Table). Smoking (hazard ratio (HR) 2.9, CI 1.7–5.0, p &lt; .01) and low baseline CD8 count (HR 0.9 for 2‐fold increase, CI 0.8–0.9, p &lt; .01) were associated with higher incidence of SPN. RT was diagnosed in 58 pts (8%) and NMSC in 138 pts (20%). 179 pts had died with 3 year overall survival of 79% (CI 76–82); the most common causes of death were CLL/RT (57%) and SPN (13%). CIR of Second Cancers Summary/Conclusion: The incidence of SPN in pts treated with BTKi for CLL is increased relative to the general population. With a 5 year CIR of NMSC and SPN of 23% and 12% respectively, these data support consideration of intensive cancer screening for CLL pts receiving BTKi. image
THU0422 COMPARISON OF PRP DERIVED GROWTH FACTOR (PRGF) VERSUS HYALURONIC ACID (HA) IN MILD TO MODERATE KNEE OSTEOARTHRITIS; A SINGLE BLIND ONE YEAR RANDOMIZED CLINICAL TRIAL STUDY
Authors: Seyed Ahmad Raeissadat, Azadeh Gharooee Ahangar, Seyed Mansoor Rayegani, Pegah Yavari
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Osteoarthritis (OA) is the most common joint disease with characteristics of progressive loss of joint cartilage. <h3>Objectives</h3> Aim of this study was to evaluate clinical outcomes of intra-articular injection of PRP derived growth factor (PRGF) versus hyaluronic acid (HA) in patients with knee osteoarthritis. <h3>Methods</h3> 102 patients with grade П or grade Ш knee OA were randomly assigned to 2 intra-articular injections of PRGF 3 weeks apart or 3 weekly injections of HA. Primary outcome was the mean change from baseline until 2, 6 and 12 months post intervention in scores of visual analog scale (VAS), WOMAC and Lequesne index. <h3>Results</h3> The mean age of patients was 57.08±7.3 in PRGF compared to 58.63±7.09 in HA group. In PRGF group, VAS decreased from 7.8±1.5 to 4.5±1.7, and from 7.8±1.1 to 6.1±1.8 in the HA group after 12 months (P&lt;0.0001). Total WOMAC score decreased from 41.96±11.71 to 27.10±12.3 (P = 0.02), and from 39.71±10.4 to 32.41±11.8 after 12 months, respectively (P &gt; 0.05). In Lequesne index, all scores were significantly decreased after 12 months in PRGF group in comparison to HA group (P&lt;0.001). <h3>Conclusion</h3> Although PRGF and HA were both effective, but PRGF injection resulted in significantly higher satisfaction, lower VAS and Lequesne pain score and improvement in function of patients with symptomatic mild to moderate knee osteoarthritis. <h3>References</h3> [1] Raeissadat SA, Rayegani SM, Tabibian E, Rahimi Dehgolan S. Intra-articular ozone injection efficacy in knee osteoarthritis: A systematic review with meta-analysis. Annals of Physical and Rehabilitation Medicine. 2018;61:e132-e3. [2] Raeissadat SA, Rayegani SM, Hassanabadi H, Fathi M, Ghorbani E, Babaee M, et al. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) versus Hyaluronic Acid (A one-year randomized clinical trial). Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2015;8:CMAMD.S17894. [3] Raeissadat SA, Rayegani SM, Ahangar AG, Abadi PH, Mojgani P, Ahangar OG. Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial. Clinical medicine insights Arthritis and musculoskeletal disorders. 2017;10:1179544117733452. <h3>Disclosure of Interests</h3> None declared
Chronic stimulation drives human NK cell dysfunction and epigenetic reprograming
Authors: Aimee Merino, Bin Zhang, Philip Dougherty, Xianghua Luo, Jinhua Wang, Bruce R. Blazar, Jeffrey S. Miller, Frank Cichocki
Journal: Journal of Clinical Investigation (2019)

A population of Natural Killer (NK) cells expressing the activating receptor NKG2C and the maturation marker CD57 expands in response to human cytomegalovirus (HCMV) infection. CD3-CD56dimCD57+NKG2C+ NK cells are similar to CD8+ memory T cells with rapid and robust effector function upon re-stimulation, persistence, and epigenetic remodeling of the IFNG locus. Chronic antigen stimulation drives CD8+ memory T cell proliferation while also inducing genome-wide epigenetic reprograming and dysfunction. We hypothesized that chronic stimulation could similarly induce epigenetic reprograming and dysfunction in NK cells. Here we show that chronic stimulation of adaptive NK cells through NKG2C using plate-bound agonistic antibodies in combination with IL-15 drove robust proliferation and activation of CD3-CD56dimCD57+NKG2C+ NK cells while simultaneously inducing high expression of the checkpoint inhibitory receptors LAG-3 and PD-1. Marked induction of checkpoint inhibitory receptors was also observed on the surface of adaptive NK cells co-cultured with HCMV-infected endothelial cells. Chronically stimulated adaptive NK cells were dysfunctional when challenged with tumor targets. These cells exhibited a pattern of epigenetic reprograming, with genome-wide alterations in DNA methylation. Our study has important implications for cancer immunotherapy and suggest that exhausted NK cells could be targeted with inhibitory checkpoint receptor blockade.
Treating Relapsed / Refractory (RR) AML with Biodegradable Anti-CD123 CAR Modified T Cells
Authors: Katherine D Cummins, Noelle Frey, Anne Marie Nelson, Aliza Schmidt, Selina Luger, Randi E. Isaacs, Simon F Lacey, Elizabeth Hexner, J. Joseph Melenhorst, Carl H June, David L Porter, Saar I Gill
Journal: Blood (2017)
Evaluation of Patients With a History of Penicillin Allergy
Authors: Yoram Faitelson, Avraham Beigelman
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 11105: Obesity Accelerates T Cell Senescence in Visceral Adipose Tissue
Authors: Kohsuke Shirakawa, Ken Shinmura, Jin Endo, Masaharu Kataoka, Tsunehisa Yamamoto, Yoshinori Katsumata, Atsushi Anzai, Sarasa Isobe, Naohiro Yoshida, Keiichi Fukuda, Motoaki Sano
Journal: Circulation (2015)

Background: Age-related changes in the immune function, particularly T-cell immune-senescence likely contribute to the nature of chronic inflammation associated with ageing-related diseases. Recently, it becomes clear that T-cell immune-senescence is not due to dysregulation of the whole T cell population, but rather the accumulation of senescence-associated T-cells. The senescence-associated T-cells are memory phenotype (MP) T-cells that constitutively express programmed cell death 1 (PD-1) on their surface. Purpose: Obesity predisposes to a lower age of onset of ageing-related diseases. We examined whether obesity accelerates T-cell senescence in visceral adipose tissue (VAT), and if so, how this impacts on VAT inflammation and glucose metabolism. Results: HFD-induced obesity causes the phenotypic changes in CD4+ T-cells similar to those observed during chronological aging process, marked by a progress increase in the number of PD-1+ MP CD4+ T-cells highly resembling senescence-associated T cells. Unique features of adipose tissue PD-1+ MP CD4+ T-cells include; expression of myeloid lineage gene, attenuated TCR-mediated proliferation, a decreased ability to produce T-cell specific lymphokines on TCR stimulation, highly biased secretin of OPN, and a rise in the levels of DNA damage response markers as well as the cyclin-dependent kinase inhibitors. The PD-1+ MP CD4+ T-cells stimulated macrophage infiltration and promoted M1 macrophage polarization, while reducing regulatory T-cells in VAT. HFD-dependent conversion of naïve T cells to PD-1+ MP T-cells in VAT depends on macrophages and B cells. Immunological depletion of PD-1+ T-cells attenuated adipose inflammation and improved insulin resistance in diet-induced obese mice, while adoptive transfer of PD-1+ MP CD4+ T-cells in VAT induced adipose inflammation and insulin resistance in non-obese mice. Analysis of human tissue suggested that a similar process may also occur in human. Interestingly, T2DM patients had more abundant PD-1+ T-cells in omental adipose tissue than non-DM patients independently BMI and age. Conclusion: Increased visceral adiposity accelerates T-cell senescence and this, in turn, leads to chronic VAT inflammation and abnormal glucose metabolism.
Fibrocyte accumulation in the airway walls of COPD patients
Authors: Isabelle Dupin, Matthieu Thumerel, Elise Maurat, Florence Coste, Edmée Eyraud, Hugues Begueret, Thomas Trian, Michel Montaudon, Roger Marthan, Pierre-Olivier Girodet, Patrick Berger
Journal: European Respiratory Journal (2019)

The remodelling mechanism and cellular players causing persistent airflow limitation in COPD remain largely elusive. We have recently demonstrated that circulating fibrocytes, a rare population of fibroblast-like cells produced by the bone marrow stroma, are increased in COPD patients during an exacerbation. We aimed to quantify fibrocyte density in situ in bronchial specimens from both control subjects and COPD patients, to define associations with relevant clinical, functional and computed tomography (CT) parameters, and to investigate the effect of the epithelial microenvironment on fibrocyte survival in vitro (“Fibrochir” study). A total of 17 COPD patients and 25 control subjects, all requiring thoracic surgery, were recruited. Using co-immunostaining and image analysis, we identified CD45 + FSP1 + cells as tissue fibrocytes, and quantified their density in distal and proximal bronchial specimens. Fibrocytes, cultured from the blood samples of six COPD patients, were exposed to primary bronchial epithelial cell secretions from control subjects or COPD patients. We demonstrate that fibrocytes are increased in both distal and proximal tissue specimens of COPD patients. The density of fibrocytes is negatively correlated with lung function parameters and positively correlated with bronchial wall thickness as assessed by CT scan. A high density of distal bronchial fibrocytes predicts the presence of COPD with a sensitivity of 83% and a specificity of 70%. Exposure of fibrocytes to COPD epithelial cell supernatant favours cell survival. Our results thus demonstrate an increased density of fibrocytes within the bronchi of COPD patients, which may be promoted by epithelial-derived survival-mediating factors.
Abstract 354: Optimization of Extracellular Vesicles Isolation From Cardiac Mesenchymal Cells
Authors: Talha A Farid, Asif R Pathan, Abdur R Khan, Marjan Nasr, Hong Li, Senthilkumar Muthusamy, Marcin Wysoczynski, Roberto Bolli
Journal: Circulation Research (2016)

Background: Cell therapy and cell derived extracellular vesicles (EVs) are promising treatment options for ischemic cardiomyopathy. Despite this increasing interest, the isolation of EVs is not standardized. The purpose of this study was to compare two most common methods of EV isolation, ultracentrifugation (UC) and polyethylene glycol precipitation (PEG); and also to test the hypothesis that PEG precipitation followed by UC (PEG+UC) offers a more efficient method of EV isolation compared to PEG precipitation or UC alone. Methods: EVs were isolated from mouse cardiac mesenchymal cells by either PEG, UC (2 cycles at 100,000g, 1 hour each), or PEG+UC (100,000g for 1 hour). Size analysis, protein content measurements and western blots (WB) were performed. Results: PEG precipitation yielded three distinct population of particles (~20-60nm, ~90-500nm &amp; &gt;1000nm – Figure 1A). UC and PEG+UC provided one distinct population of EVs (90-500nm). With PEG precipitation, the highest concentration of particles obtained were in the range of 20-60nm (~99%, Figure 1B). With PEG+UC, these smaller particles were cleared yielding an uncontaminated EV population (90-500nm). PEG precipitation yielded highest content of protein followed by PEG+UC (Figure 1C). WB demonstrated weak expression of EV markers with PEG precipitation and enriched markers with UC &amp; PEG+UC (Figure 1D). Conclusion: PEG precipitation yields least pure population of EVs with highest protein contamination, likely from precipitation of soluble proteins. UC provides pure EV population with low yield. PEG precipitation followed by UC provides the highest yield of EVs while maintaining EV purity.
THU0120 RHEUMATIC DISEASE COMORBIDITY INDEX IMPACT ON DISEASE ACTIVITY IN PATIENTS ENROLLED IN KUWAIT REGISTRY OF RHEUMATIC DISEASES (KRRD)
Authors: YASER Ali, Khulood Saleh, Ahmed Enizi, Fatemah Abutiban, Adel Al-Awadhi, Waleed Al-Kandari, Eman Hasan, Hebah Alhajeri, Mohammed Hussain, Ahmed Alsaber, Sawsan Hayat, Ali Aledei, Adeeba Herz, Aqeel Ghanem
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Its known that the presence of certain comorbidities in patients with Rheumatoid arthritis (RA) can have an impact on the chance of achieving low disease activity (LDA). <h3>Objectives:</h3> The purpose of this study was to examine the association of different comorbidities with low disease activity index in patients enrolled in KRRD. <h3>Methods:</h3> The database of KRRD was used to include patients with RA and multiple visits. Comorbid conditions were collected at enrollment by the treating rheumatologist and modeled using the Rheumatic Disease Comorbidity index (RDCI) score, and by individual comorbid condition. Disease activity (DAS28) was assessed at routine clinic visits. Associations of comorbidity measures with disease activity over 4 years of follow up were examined using multivariable linear models. The odds of ever achieving DAS28 low disease activity (&lt;3.2) were examined using multivariable logistic regression. <h3>Results:</h3> Among 1511 participants with mean age of 52 (SD 12) years, RA duration 8 (SD 6) years, 60.7% female, 77.1% RF positive, 64.6% anti-CCP positive, and 10.8% with smoking history, 1.29 had a RDCI. Hypertension (21%), diabetes mellitus (21%), hyperlipidemia (12%), cardiovascular (CV) disease (3.6%) and interstitial lung disease (ILD) (1.1%), were the most prevalent comorbidities. Select individual comorbidities, including DM, kidney disease and COPD, were more closely associated with unfavorable longitudinal disease activity, and achievement of low disease activity status. Correlation test between DAS28 and all comorbidities showed signification negative association for achieving low disease activity if the patient has history of diabetes mellitus, COPD or kidney disease. <h3>Conclusion:</h3> DM, kidney disease and COPD but not composite comorbidity scores, are associated with higher measures of disease activity and lower odds of achieving low disease activity status in RA patients enrolled in KRRD registry. <h3>Disclosure of Interests:</h3> None declared
Use of In-Laboratory Sleep Studies in the Veterans Health Administration and Community Care
Authors: Lucas M. Donovan, Scott S. Coggeshall, Laura J. Spece, Matthew F. Griffith, Brian N. Palen, Elizabeth C. Parsons, Jeffrey A. Todd-Stenberg, Thomas J. Glorioso, Evan P. Carey, Laura C. Feemster, Steven B. Zeliadt, Susan Kirsh, David H. Au
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
AB1256 HIGH PREVALENCE OF DEPRESSION IN RHEUMATIC DISEASES: CASE-CONTROL STUDY
Authors: Dionicio Ãngel Galarza-Delgado, José Ramón Azpiri-López, Iris Jazmin Colunga-Pedraza, Karla Paola Cuéllar-Calderón, Ileana Cecilia Reynosa-Silva, Marielva Castro-González, Carolina Marlene Martínez-Flores, Raymundo Pineda
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Prevalence of depression is higher in subjects with rheumatic diseases (RD) when compared to other general medical conditions. It's associated with chronic pain and long-term medical treatment. The Patient Health Questionnaire 9 (PHQ-9) is an extensively validated screening tool, with a negative predictive value of 99%; it has several advantages, like being self-applied and able to be used by any clinician. Currently there are no trials using this screening tool in Mexican rheumatic patients. <h3>Objectives:</h3> To determine the prevalence of depression in a group of rheumatic subjects and compare it to non-rheumatic controls. <h3>Methods:</h3> An observational, cross-sectional study was designed. Subjects with RD attending an outpatient clinic were consecutively recruited. A complete clinical history with information about exercise history, and the PHQ-9 screening tool were performed to every subject. Subjects without RD were recruited as controls. Descriptive analysis was done using frequencies (%) and median (q25-q75). Comparisons were done using Chi-square and Mann-U Whitney's test, considering only p&lt;0.05 as significant. <h3>Results:</h3> A total of 269 subjects were included. Demographic characteristics are shown in Table 1. In the RD group, a higher percentage were female (p&lt;0.001) and had a higher median age (p&lt;0.001). A higher prevalence of depression was found in the RD group (p&lt;0.002). Regarding exercise history, subjects with an inactive lifestyle had a higher prevalence of depression (p&lt;0.001). This remained significant after evaluating only subjects with RD (p&lt;0.007) and controls (p&lt;0.003). <h3>Conclusion:</h3> Patients with RD have a higher prevalence of depression than non-rheumatic controls (p&lt;0.001). An inactive lifestyle was associated with a higher prevalence of depression in our cohort, both in RD subjects and in controls (p&lt;0.001). This is the first study that evaluates the PHQ-9 screening tool in Mexican patients with RD. The physicians should be aware of it and use screening tools to detect depression disorders and provide an adequate treatment. <h3>References</h3> [1] O'Malley PG, Jackson JL, Kroenke K, Yoon IK, Hornstein E, Dennis GJ. The value of screening for psychiatric disorders in rheumatology referrals. Arch Intern Med 1998;158:2357-62. [2] Ohayon MM, Schatzberg AF. Using chronic pain to predict depressive morbidity in the general population. Arch of Gen Psychiatry 2003;60:39-47. [3] Anyfanti, P., et al. Depression, anxiety, and quality of life in a large cohort of patients with rheumatic diseases: common, yet undertreated. Clin Rheumatol DOI 10.1007/s10067-014-2677-0 <h3>Disclosure of Interests:</h3> None declared
Solutions to Reduce Unnecessary Imaging—Reply
Authors: Ohad Oren, Electron Kebebew, John P. A. Ioannidis
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal