tbuckley/cabot-search huggingface dataset:
OP0074 TOFACITINIB PROMOTES FUNDAMENTAL PROCESSES OF BONE HEALING
Authors: Timo Gaber, Antonia Brinkman, Alexandra Damerau, Moritz Pfeiffenberger, Lisa Ehlers, Frank Buttgereit, Paula Hoff
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Inflammatory diseases like rheumatoid arthritis (RA) and anti-inflammatory treatment of RA with glucocorticoids (GC) or NSAIDS negatively influence bone metabolism and fracture healing. Janus kinase (Jak) inhibition with tofacitinib has been demonstrated as a potent anti-inflammatory therapeutic agent in the treatment of RA but its impact on the fundamental processes of bone regeneration such as recruitment of human mesenchymal stromal cells (hMSCs) and chondrogenesis, osteogenesis and osteoclastogenesis is still controversial and in part elusive. <h3>Objectives</h3> Therefore, in this study, we aim to examine the effects of Tofacitinib on processes of bone healing under reduced oxygen availability mimicking the in vivo situation of the fracture gap. <h3>Methods</h3> To this end, we analyzed the influence of Tofacitinib on the (i) invasion of hMSCs towards TNFα using a trans-well assay, (ii) chondrogenic differentiation of hMSCs in a 3D-micro-mass culture under hypoxic conditions, (iii) osteogenic differentiation of hMSCs, (iv) M-CSF/RANKL-mediated differentiation of isolated monocytes towards osteoclasts and (v) hypoxia-mediated target gene expression in non-differentiated, osteogenic and chondrogenic differentiated hMSCs. <h3>Results</h3> We demonstrate that Tofacitinib dose-dependently promotes the recruitment of hMSCs under hypoxia but inhibits recruitment of hMSCs under normoxia. With regard to the chondrogenic differentiation of hMSCs, we observed that Tofacitinib did not inhibit survival and at therapeutic relevant doses of 10-100nM. Moreover, Tofacitinib dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast survival and differentiation under hypoxic conditions. We show that Tofacitinib does not affect chondrogenic HIF target gene expression but increases HIF target gene expression in human osteogenic differentiated MSCs. <h3>Conclusion</h3> We conclude from our data, that Tofacitinib may influence bone healing by promotion MSC recruitment into the hypoxic microenvironment of the fracture gap, does not interfere with the cartilaginous phase of the soft callus phase of fracture healing process. We assume that Tofacitinib may promote bone formation and reduce bone resorption which could in part explain the positive impact on bone erosions by Tofacitinib. Thus, we hypothesize that it will be unnecessary to stop this medication in case of fracture and suggest that positive effects on osteoporosis are likely. <h3>Acknowledgement</h3> Funded by an unrestricted grant provided by Pfizer. <h3>Disclosure of Interests</h3> Timo Gaber Grant/research support from: Pfizer, Antonia Brinkman: None declared, Alexandra Damerau: None declared, Moritz Pfeiffenberger: None declared, Lisa Ehlers: None declared, Frank Buttgereit: None declared, Paula Hoff Grant/research support from: Pfizer
Abstract 12237: Blunted Responses to Heart Failure Symptoms in Adults with Mild Cognitive Dysfunction
Authors: Christopher S Lee, Jill M Gelow, Diana S Woodruff-Pak, Jennifer Green, Anne G Rosenfeld, Antony Y Kim
Journal: Circulation (2011)

Introduction: The clinical impact of mild cognitive dysfunction in heart failure (HF) is unknown. We hypothesized that mild cognitive dysfunction would be associated with poor HF self-care behavior...
Becoming a Statistic in the Middle of an Epidemic—A Call to Consider Alternate Risk Factors for Early-Onset Colorectal Cancer—In Reply
Authors: Po-Hong Liu, Edward L. Giovannucci, Yin Cao
Journal: JAMA Oncology (2019)

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Heart Failure, Shared Decision-making, and Social Determinants of Health
Authors: Kimberly R. Enard, Paul J. Hauptman
Journal: JAMA Cardiology (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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
Association of Anxiety With High-Cost Health Care Use Among Individuals With Type 2 Diabetes
Authors: Esti Iturralde, Felicia W. Chi, Richard W. Grant, Constance Weisner, Lucas Van Dyke, Alix Pruzansky, Sandy Bui, Philip Madvig, Robert Pearl, Stacy A. Sterling
Journal: Diabetes Care (2019)

OBJECTIVE People with type 2 diabetes vary greatly in their use of high-cost health care resources. We examined the association of anxiety with high-cost use after accounting for depression and medical comorbidity. RESEARCH DESIGN AND METHODS Using electronic health record data, we assessed past anxiety diagnosis, health care use and costs, demographics, comorbidities, and diabetes control status and complications during 2008–2012 for 143,573 adult members of an integrated health care system with type 2 diabetes. Multivariable regression models estimated associations between anxiety and emergency department (ED) use, total hospitalization costs, and high-cost status (i.e., incurring total health care costs in the top 20% among all system members). RESULTS During 2008–2011, 12.9% of participants received a diagnosis of anxiety, of whom 52.9% also had received a depression diagnosis. After adjustment for covariates including depression, anxiety was positively related to the number of ED visits in 2012 (incidence rate ratio 1.27; 95% CI 1.21, 1.34), the likelihood of visiting the ED on a chronic, frequent basis during 2010–2012 (odds ratio 2.55; 95% CI 1.90, 3.44), and high-cost status in 2012 (odds ratio 1.29; 95% CI 1.23, 1.36), but anxiety was not related to total hospitalization costs in 2012 (relative cost ratio 1.06; 95% CI 0.94, 1.21; P = 0.33). CONCLUSIONS Anxiety is highly comorbid with depression among individuals with type 2 diabetes and is independently associated with high-cost resource use. Strategies to improve anxiety management among people with diabetes hold the potential to also reduce health care costs.
PF604 THE AUSTRALASIAN LEUKAEMIA AND LYMPHOMA (ALLG) GROUP MM17 TRIAL: RESPONSE ADAPTIVE SALVAGE WITH CARFILZOMIB‐THALIDOMIDE‐DEXAMETHASONE FOR MULTIPLE MYELOMA PATIENTS FAILING FRONT‐LINE BORTEZOMIB
Authors: A. Spencer, H. Quach, N. Horvath, I. Kerridge, F. Yuen, E. Lee, E. Morris, A. Kalff, K. Bergin, S. Sirdesai, M. Gorniak, S. Mithraprabhu, T. Khong, J. Reynolds
Journal: HemaSphere (2019)

Background: Over 90% of transplant eligible newly diagnosed multiple myeloma (TE‐NDMM) patients (pts) in Australia are induced with bortezomib (V)‐ cyclophosphamide‐dexamethasone. Of these, 15% demonstrate either a sub‐optimal response (&lt;partial response [PR]) (SOR) or primary refractoriness (1REF). These pts experience short progression free (PFS) and overall survival (OS), thus representing an area of ongoing unmet medical need. Aims: The ALLG MM17 trial was designed to evaluate an early response adaptive switch to carfilzomib‐thalidomide‐dexamethasone (KTd) and to define the mutational spectrum of disease in TE‐ NDMM patients failing V‐induction. Methods: Pts were either SOR (defined as 2on D1, 2, 8, 9, 15 and 16 of each 28‐day cycle (27 mg/m 2 D1 and 2 of cycle 1); T 100 mg D1–28; and, d 40 mg on D1, 8, 15, and 22 of each cycle. Pts were planned to receive KTd x 4 cycles then undergo re‐staging. Those achieving a stringent complete response (sCR) (morphologically normal bone marrow [BM], IF negativity, normalisation of the involved light chain isotype) proceeded to a MEL200 ASCT. Those with Results: Fifty pts were recruited between 9/2016 and 4/2018. Data cut‐off date was November 7, 2018 with the reverse‐Kaplan‐Meier estimate of the median potential follow‐up for survival being 14.8 months (95% CI: 9.7 – 17.8 months). Median age was 50 years (36–71) with 72% males. Median time from initial therapy to study entry was 4 months with disease status at entry of SOR in 26 (66%) (&lt;MR n = 13, &lt;PR n = 13) and 1REF in 13 (33%). EMC92 stratification demonstrated high‐risk disease in 48%. The tumour suppressor CDC27 (Anaphase‐promoting complex E3 ubiquitin ligase) was the most commonly mutated gene at study entry with a high proportion of patients also manifesting potentially targetable lesions – ATR, ATM, PIK3CA, FGFR3 and KRAS. The median number of pre‐ASCT KTd cycles was 6 (range 1 to 6). ORR was 78% (95% CI: 64–87%) ∗ ‐ sCR 12%, CR 6%, VGPR 38% and PR 22%. On an intention‐to‐treat basis 32% of pts were MRD neg pre‐ASCT, 40% at day 100 post‐ASCT and 51% post KTd consolidation. Ten pts have progressed, 7 with highly aggressive extra‐medullary disease. No patient that achieved MRD negativity has progressed. Neither median PFS nor OS have been reached. Summary/Conclusion: KTd produces high response rates and MRD negativity in TE‐NDMM patients failing V‐based induction. TAS revealed a novel mutational spectrum consistent with treatment selection of V‐resistant sub‐clones likely present at diagnosis.
Patients’ views of wearable devices and AI in healthcare: findings from the ComPaRe e-cohort
Authors: Viet-Thi Tran, Carolina Riveros, Philippe Ravaud
Journal: npj Digital Medicine (2019)

Wearable biometric monitoring devices (BMDs) and artificial intelligence (AI) enable the remote measurement and analysis of patient data in real time. These technologies have generated a lot of "hype," but their real-world effectiveness will depend on patients' uptake. Our objective was to describe patients' perceptions of the use of BMDs and AI in healthcare. We recruited adult patients with chronic conditions in France from the "Community of Patients for Research" (ComPaRe). Participants (1) answered quantitative and open-ended questions about the potential benefits and dangers of using of these new technologies and (2) participated in a case-vignette experiment to assess their readiness for using BMDs and AI in healthcare. Vignettes covered the use of AI to screen for skin cancer, remote monitoring of chronic conditions to predict exacerbations, smart clothes to guide physical therapy, and AI chatbots to answer emergency calls. A total of 1183 patients (51% response rate) were enrolled between May and June 2018. Overall, 20% considered that the benefits of technology (e.g., improving the reactivity in care and reducing the burden of treatment) greatly outweighed the dangers. Only 3% of participants felt that negative aspects (inadequate replacement of human intelligence, risks of hacking and misuse of private patient data) greatly outweighed potential benefits. We found that 35% of patients would refuse to integrate at least one existing or soon-to-be available intervention using BMDs and AI-based tools in their care. Accounting for patients' perspectives will help make the most of technology without impairing the human aspects of care, generating a burden or intruding on patients' lives.
PB1884 HIGH CXCR3 AND CXCR5 DISTINGUISH IGHVMUT FROM IGHVUNMUT CHRONIC LYMPHOCYTIC LEUKEMIA: EVIDENCE FROM CD5HIGH AND CD5LOW CLONES
Authors: G. Gabcova, G. Manukyan, T. Papajik, Z. Mikulkova, R. Urbanova, M. Kudelka, V. Smotkova Kraiczova, S. Zehnalova, P. Turcsanyi, E. Kriegova
Journal: HemaSphere (2019)

Background: Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) demonstrate heterogeneity in their molecular and functional characteristics. Given the dynamic variability of CD5 expression and its link to the proliferative pool of neoplastic cells, more detailed characterization of CLL cell subpopulations are needed. Aims: To further characterize the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5 high and CD5 low neoplastic clones in peripheral blood in CLL. Methods: Study cohort consisted of CLL patients (n = 60) subgrouped according to the IgHV mutational status ( IgHV mut , n = 24; IgHV unmut , n = 36). Chemokine receptors and adhesion molecules on CD5 high and CD5 low cell subpopulations, determined by CD5/CD19 co‐expression, in peripheral blood were assessed by a six‐colour flow cytometry analysis on a BD FACSCanto II (Becton Dickinson). Data were analysed by basic statistics and patient similarity networks. Results: CD5 high cell subpopulation expressed high levels of CXCR3 ( P &lt; 0.001), CXCR5 ( P = 0.005), CCR7 ( P = 0.013), CCR10 ( P = 0.001), CD62L ( P = 0.031) compared to CD5 low cells expressing high levels of CXCR4 ( P &lt; 0.001). When comparing IgHV mut from IgHV unmut patients, high‐levels of CXCR3 and CXCR5 on the whole neoplastic population as well as CD5 high and CD5 low subpopulations were detected in the IgHV mut patients. Multivariate patient similarity networks confirmed the significance of high CXCR3 levels predominantly on CD5 low cells from IgHV mut patients. Summary/Conclusion: Our analysis revealed that CD5 high and CD5 low neoplastic clones from IgHV mut and IgHV unmut differed mainly by the expression of CXCR3. Further characterization of neoplastic cell heterogeneity and role of CXCR3 will advance our understanding of CLL biology and its clinical relevance. Grants: MZ ČR VES16‐32339A, IGA UP_2019_014, IGA_LF_2019_001, MH CZ–DRO (FNOL, 00098892)
AB1151 APPLICATION OF ULTRASOUND TO DISTINGUISHING PMR FROM POLYARTHRALGIA
Authors: Tomohiro Kawaguchi, Michihiro Ogasawara, Ken Yamaji, Naoto Tamura
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Japan is the world's most aged country. The number of patients with polymyalgia rheumatica (PMR) is expected to increase more. Classification criteria including ultrasound findings were published in 2012, but the ability to differentiate PMR from rheumatoid arthritis (RA) was not significant. We will clarify whether recently reported ultrasound findings (1, 2) which could be characteristic in PMR are helpful for distinguishing from other diseases and treatment outcome in suspected PMR patients. <h3>Objectives</h3> Patients who were clinically suspected of PMR and underwent ultrasound examination from March 2015 to July 2018. <h3>Methods</h3> Recorded ultrasound images were retrospectively interpreted by the ultrasound expert, who was blind for clinical information. They were classified into three groups of PMR, RA, others/no inflammation. Initial dose of glucocorticoid (GC), therapeutic response, presence or absence of relapse, and concomitant medications were collected and compared among the 3 groups. Cases in which steroids had already been used before ultrasound examination were excluded from the analysis. <h3>Results</h3> The number of subjects was 81, and the number of ultrasound examination was 88. The ultrasound expert classified 29 PMR, 20 RA, 3 other/no inflammation. 18.5% (15/81) of the subjects were improved with no GC and relapse. The average prednisolone (PSL) dose was 15.3 mg in the PMR group, and 9.7 mg in the RA group. Concomitant medications were introduced in 31% (9/29) of PMR group, in 65% (13/20) of RA group. <h3>Conclusion</h3> Ultrasound is useful for distinguishing PMR from seronegative RA and other arthralgia. These findings showed that ultrasound is useful for the proper use of GC and concomitant medications. <h3>References</h3> [1] Suzuki T, Yoshida R, Hidaka Y, Seri Y. Proliferative Synovitis of the Shoulder Bursae is a Key Feature for Discriminating Elderly Onset Rheumatoid Arthritis Mimicking Polymyalgia Rheumatica From Polymyalgia Rheumatica. Clin Med Insights Arthritis Musculoskelet Disord 2017;10: 1179544117745851. [2] Suzuki T, Yoshida R, Okamoto A, Seri Y. Semiquantitative Evaluation of Extrasynovial Soft Tissue Inflammation in the Shoulders of Patients with Polymyalgia Rheumatica and Elderly-Onset Rheumatoid Arthritis by Power Doppler Ultrasound. Biomed Res Int 2017;2017: 4272560. <h3>Disclosure of Interests</h3> Tomohiro Kawaguchi: None declared, Michihiro Ogasawara: None declared, Ken Yamaji: None declared, Naoto Tamura Grant/research support from: Astellas Pharma Inc., Asahi Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. LTD, Eisai Inc., :Takeda Pharmaceutical Company Ltd., Speakers bureau: Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., :Mitsubishi Tanabe Pharma Co.
Abstract 15870: Weight Gain Vs Stable Obesity in Middle Age is Associated With Higher Burden of Cardiometabolic Disease and Overall Comorbidity
Authors: Rebecca T Levinson, Eric Farber-Eger, Megan E Vogel, Heidi J Silver, Nancy J Brown, Kevin D Niswender, Nancy J Cox, Joshua A Beckman, Quinn S Wells
Journal: Circulation (2018)

Background: The prevalence and consequences of additional weight gain among already obese individuals in middle age is unknown. Studies assessing the consequences of obesity and weight gain often f...
5-Year Prognostic Value of Quantitative Versus Visual MPI in Subtle Perfusion Defects
Authors: Yuka Otaki, Julian Betancur, Tali Sharir, Lien-Hsin Hu, Heidi Gransar, Joanna X. Liang, Peyman N. Azadani, Andrew J. Einstein, Mathews B. Fish, Terrence D. Ruddy, Philipp A. Kaufmann, Albert J. Sinusas, Edward J. Miller, Timothy M. Bateman, Sharmila Dorbala, Marcelo Di Carli, Balaji K. Tamarappoo, Guido Germano, Damini Dey, Daniel S. Berman, Piotr J. Slomka
Journal: JACC. Cardiovascular imaging (2019)
AB0506 MICRORNA A POTENTIAL MARKER OF LUPUS ACTIVITY IN AN EGYPTIAN LUPUS COHORT
Authors: Marwa Elkhalifa, Manal Tayel, Magdy Zehairy, Ahmed Elkeriae, Dalal Mohamed Nasr Eldin Elkaffash, Nahed Baddour
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> MicroRNAs play central roles in different stages of cellular activity, as well as contribute extensively to multifaceted aspects of systemic lupus erythematosus (SLE) pathogenesis. Screening from approximately a thousand human miRNAs, studies have concluded that their dysfunction has been related to the development and activity of diseases.<sup>(1)</sup> In addition, The expression levels of miRNAs in serum are stable, reproducible, and consistent. Thus, testing serum microRNA sequence provide novel biomarkers and potential therapeutic strategies in SLE patients.<sup>(2)</sup> <h3>Objectives:</h3> To study the role of micro-RNA-142-3p expression in SLE in an Egyptian cohort and its role as a potential biomarker of lupus activity. <h3>Methods:</h3> Expression of microRNA- 142-3p extracted from peripheral blood mono-nuclear cells determined using quantitative reverse transcription–polymerase chain reaction assay. A total of 60 plasma samples were obtained from 30 SLE patients without clinical and laboratory evidence of lupus nephritis (group A) and 30 SLE patients with clinical and laboratory evidence of lupus nephritis confirmed by renal biopsy (group B). <h3>Results:</h3> We found a significant correlation between micro-RNA-142-3p expression levels and serum level of anti ds-DNA in both group A (p=0.007) and group B (p=019). We also found no significant correlation between micro-RNA-142-3p expression levels and C3 (p=0.399) &amp; C4 (p=0.375) in group A, while there was a significant correlation in group B with both C3 (P=0.005) and C4 (P=0.002).In addition to, We demonstrated a significant correlation between micro-RNA-142-3p expression levels and SLEDAI score in both group A (P=0.001) and group B (P=0.007). <h3>Conclusion:</h3> The expression level of micro-RNA-142-3p could be considered a potential activity marker in SLE patients with and without lupus nephritis. <h3>References</h3> [1] Amarilyo G, La Cava A. miRNA in systemic lupus erythematosus. Clin Immunol 2012; 144:26–31. [2] Wang Z, Chang C, Peng M, Lu Q. Translating epigenetics into clinic: focus on lupus. Clin Epigenetics 2017; 9:78. <h3>Disclosure of Interests:</h3> None declared
FRI0314 SENSITIVITY TO CHANGE AND RESPONSIVENESS TO TREATMENT OF RENAL RESISTIVE INDEX (IRR) IN SYSTEMIC SCLEROSIS (SSC)
Authors: Cosimo Bruni, Edoardo Rosato, Antonietta Gigante, Vanessa Maestripieri, Giulia Tesei, Marco Chiostri, Gemma Lepri, Silvia Bellando Randone, Serena Guiducci, Sergio Castellani, Maria Boddi, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> RRI may identify any problem with the blood flow in the renal artery and in the parenchyma. It was shown to be increased in SSc patients and being in relationship with both vascular and fibrotic SSc-related manifestations. Objectives: to test sensitivity to change and responsiveness to treatment of RRI in SSc. Methods: patients fulfilling the 2013 ACR/EULAR classification creteria for SSc were enrolled from two SSc-care units, if RRI was determined at least twice since being diagnosed. Data regarding SSc clinical manifestations, instrumental and laboratory evaluation for renal, cardiac and cardiovascular involvement, as well as ongoing immunosuppressive and vasoactive/vasodilating treatment, were collected both at baseline and follow-up RRI measurements. <h3>Results</h3> 230 patients [aged 57 (48-67) years, 12.6% males] were enrolled in the study, with baseline RRI value of 0.68 (IQR 0.07). In a mean 3.4 years follow-up, RRI showed a median change (ΔRRI) of +0.02 (IQR 0.05). ΔRRI was significantly correlated with ΔsPAP (R=0.173, p=0.023) and it was significantly higher in patient with new onset of pulmonary arterial hypertension (0.08 ± 0.02 vs 0.03 ± 0.05; p=0.038). On Cox univariate regression analysis, time from disease onset, ΔssPAP and ΔRRI predicted new PAH, while ΔsPAP was the only independent predictors at multivariate regression analysis. Regarding treatment, Sildenafil exposure determined a significantly lower increase in ΔRRI, with a progressive long-term effect. Conversely, CCBs and Iloprost treated patients showed a significantly higher increase of ΔRRI, which was determined by a higher DU burden. No difference was seen when immunosuppressive treatment was evaluated. <h3>Conclusion</h3> RRI is sensitive to change and reflects, in particular, the worsening of cardio-pulmonary vascular involvement (increase in ΔsPAP and new PAH onset). Moreover, it shows a possible protective effect of Sildenafil in reducing pulmonary vasculature manifestations. <h3>Disclosure of Interests</h3> Cosimo Bruni: None declared, Edoardo Rosato: None declared, Antonietta Gigante: None declared, Vanessa Maestripieri: None declared, Giulia Tesei: None declared, Marco Chiostri: None declared, Gemma Lepri: None declared, Silvia Bellando Randone: None declared, Serena Guiducci: None declared, Sergio Castellani: None declared, Maria Boddi: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen