tbuckley/cabot-search huggingface dataset:
Final results of a phase II multicenter trial of HF10, a replication-competent HSV-1 oncolytic virus, and ipilimumab combination treatment in patients with stage IIIB-IV unresectable or metastatic melanoma.
Authors: Robert Hans Ingemar Andtbacka, Merrick I. Ross, Sanjiv S. Agarwala, Matthew H. Taylor, John T. Vetto, Rogerio Izar Neves, Adil Daud, Hung T. Khong, Richard S. Ungerleider, Maki Tanaka, Kenneth F. Grossmann
Journal: Journal of Clinical Oncology (2017)

9510 Background: HF10 is a bioselected replication-competent oncolytic virus derived from HSV-1. Herein, we report the safety and efficacy data of HF10 + ipilimumab (ipi) combination treatment in a Phase II trial in melanoma. Methods: Key entry criteria: age ≥ 18 yrs, ECOG ≤ 2, Stage IIIB, IIIC, or IV unresectable melanoma, ipi naïve (IV administration) and measurable non-visceral lesion(s) suitable for injection. HF10 injected into single or multiple tumors (1 x 10 7 TCID 50 /mL/dose, up to 5mL depending on tumor size and number); 4 injections q1wk; then up to 15 injections q3wk. Four ipi IV infusions (3 mg/kg; concurrent with HF10) were administered q3wk. AEs assessed per CTCAE 4.0. Tumor responses were assessed per mWHO and irRC at 12, 18, 24, 36 and 48 wks for patients (pts) continuing on HF10 monotherapy. Primary endpoint was Best Overall Response Rate (BORR) at 24 wks. Dose limiting toxicity (DLT) defined as ≥ G3 non-hematologic/hematologic toxicity, ≥ G2 neurologic toxicity, or allergic event occurring within 1 st 3wks of therapy. Results: Of 46 pts enrolled and treated: 59% men, median age 67 yrs (range 28 to 91); disease stage 20% IIIB, 43% IIIC and 37% IV; 57% were treatment naïve and 43% with ≥ 1 prior cancer therapy for unresectable/metastatic melanoma. Most HF10-related AEs were ≤G2, similar to HF10 monotherapy. No DLTs were reported. 37% had ≥G3 AEs, the majority due to ipi. HF10-related ≥G3 AEs (n=3) were embolism, lymphedema, diarrhea, hypoglycemia, and groin pain. Of the 44 efficacy evaluable pts per irRC, BORR at 24 weeks was 41% (16% irCR and 25% irPR); disease stability rate was 68% (16% irCR, 25% irPR and 27% irSD). As of Feb 06, 2017, median PFS was 19 months and median overall survival was 21.8 months. Conclusions: The combination HF10 and ipilimumab treatment demonstrated a favorable benefit/risk profile and encouraging antitumor activity in pts with stage IIIB, IIIC, or IV unresectable or metastatic melanoma. Clinical trial information: NCT02272855.
Progress Stalls in Improving Vaccine Coverage Rates
Authors: M.J. Friedrich
Journal: JAMA (2017)

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
THU0010 Altered mirnas profiles in plasma-derived exosome of patients with ankylosing spondylitis by small rna-seq analysis
Authors: Y Huang, T Li, Z Huang, W Deng, S Zheng, X Guo, Z Huang
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic inflammatory disease, which is difficult to diagnose in the early stages. Increasing evidences have shown that MicroRNAs (miRNAs) may serve as novel biomarkers for AS. Exosome can function as vehicles to deliver miRNAs in body fluids including saliva and plasma. However, the relationship between exosome-delivered miRNAs and AS has yet to be determined. <h3>Objectives</h3> The aim of this study is to detect the altered miRNAs profiles of plasma-derived exosome in AS patients by small RNA-Seq Analysis. <h3>Methods</h3> Ribo<sup>TM</sup> kit was used to isolate exosome. Small RNA Sample Pre Kit was used to build libraries in 3 AS patients and 3 healthy volunteers (HV), following by IlluminaHiSeq platform sequencing and bioinformatics analysis. Quantitative reverse-transcription PCR (qRT-PCR) was used to confirm the expression of the highly-expressed miRNA in another 10 AS patients and 10 HV, and receiver-operator characteristic (ROC) curve was used to evaluate the diagnostic value of miRNAs. <h3>Results</h3> Small RNA-Seq analysis showed that the Q30 value of HV and AS patients were higher than 95% (Fig.1-A). The amount of miRNA in HV and AS patients were (509.667±77.501) and (632.000±43.555). 80 up-regulated and 19 down-regulated exosomal miRNAs were identified in AS patients, compared with HV (|log2Ratio|&gt;1, <i>P</i> &lt;0.05) (Fig.1-B-C). The target genes of the 34 highly-expressed miRNAs from the 99 differently-expressed miRNAs were 7869, and the main function of these target genes are involved in the regulation of endocytosis and protein modification process analyzed by GO and KEGG. The qRT-PCR results indicated that the expression level of miRNA21–5P and miRNA423–5P in AS patients were (2.940±1.572) and (2.520±1.401) times higher than that of HV (Fig.1-D-E). ROC curve analysis showed that miRNA21–5P and miRNA423–5P had significant diagnostic value for AS with the AUC of 0.890 (CI95%: 0.723–1.057) and 0.835 (CI95%: 0.621–1.039) respectively (Fig.1-F). <h3>Conclusions</h3> The miRNAs profiles in plasma-derived exosome of AS patients are significant different from HV. miRNA21–5P and miRNA423–5P are higher expressed in AS patients. Thus, plasma-derived exosomal miRNAs might be reliable biomarkers to identify AS. <h3>References</h3> El MA. Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. Eur J Intern Med, 2011, 22(6):554–60. <h3>Disclosure of Interest</h3> None declared
SAT0245 Serum ifn gama may predict therapeutic effect of mesenchymal stem cells transplantation in systemic lupus erythematosus patients
Authors: D Wang, L Sun
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Umbilical cord (UC) derived mesenchymal stem cells (MSCs) show immunoregulatory properties on various immune cells and display clinical effect on lots of autoimmune disease like systemic lupus erythematosus (SLE). <h3>Objectives</h3> The aim of this study is to investigate the effect of SLE environment on UC MSCs and to observe the possible serum biomarker to predict the therapeutic effect. <h3>Methods</h3> UC MSCs were co-cultured with peripheral blood mononuclear cells (PBMC) from active lupus patients at a ratio of 1:4. The proliferation, apoptosis and surface markers of UC MSCs were observed. UC MSCs functional molecules were assessed by real-time PCR and the signaling pathways were analyzed by western blot. Different recombinant cytokines were used to stimulate UC MSCs <i>in vitro</i> and the functional factors were determined by real-time PCR. In the last, twenty-six patients with SLE, refractory to conventional therapies, were given UC MSCs transplantation. The clinical effect was followed-up for one year to classify responder and non-responder groups, and baseline serum cytokines were analyzed by ELISA. <h3>Results</h3> The co-culture of lupus patients PBMC had no effect on UC MSCs surface markers and apoptosis, but promoted MSCs proliferation. Lupus PBMC were more prone to stimulate UC MSCs to secret VEGF as well as CXCL-12, compared to PBMC from normal controls. Furthermore, lupus PBMC activated Akt, IκB and Stat5 signaling pathways in UC MSCs but not affect Erk1/2 and Smad1/5/8 pathways. When stimulated by different cytokines, we found that interferon γ (IFN-γ) was still the most important cytokine to induce IDO1 as well as IDO2 productions in UC MSCs; both had dose-dependent manners. Moreover, our clinical study showed that baseline higher levels IFN-γ might predict a good response to MSCs transplantation in active lupus patients. <h3>Conclusions</h3> Baseline IFN-γ levels may predict clinical response to MSCs therapy for active lupus patients, which will help us to choose appropriate patient for clinical transplantation. <h3>Disclosure of Interest</h3> None declared
Assessment of Hospital Emergency Department Response to Potentially Infectious Diseases Using Unannounced Mystery Patient Drills — New York City, 2016
Authors: Mary M.K. Foote, Timothy S. Styles, Celia L. Quinn
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Every September, CDC, private and public health institutions, and approximately 3,000 government organizations support preparedness efforts and encourage Americans to take action before, during, and after an emergency.Every community in the United States should be ready to respond to an infectious disease outbreak, chemical or radiological release, or natural disaster (1).Public health systems should have the capacity to scale up and respond to the varying demands of public health emergencies (2).Many emergencies happen without warning; it is important for all persons to take steps ahead of time to keep themselves and their loved ones safe and healthy.Research shows that only 46% of persons think a natural disaster is likely to occur in their community (3).It is vital to take immediate and appropriate actions in the event of an emergency.This year, CDC's Office of Public Health Preparedness and Response focuses on empowering individuals to better prepare for public health emergencies.The 2017 theme "The Power of Preparedness" highlights the importance of building and updating an emergency kit, having and reviewing an emergency plan, inspiring others to prepare, and taking immediate action to save lives.This issue of MMWR includes a report describing a series of unannounced mystery patient drills that were conducted in New York City emergency departments to assess response to potential infectious disease threats.Individual and community preparedness resources are available at https://www.cdc.gov/phpr/preparedness_month.htm.
AB0336 Magnetic resonance imaging-assessed synovial and bone changes in hand and wrist joints of rheumatoid arthritis patients
Authors: KA Lee, S-H Min, T-H Kim, S-H Lee, H-R Kim
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Magnetic resonance imaging (MRI) is a sensitive and useful method for the detection of synovitis and joint destruction in rheumatoid arthritis (RA) patients. However, the patterns of MRI-detected bone erosion, bone marrow edema (BME), synovitis, and tenosynovitis have received insufficient attention. <h3>Objectives</h3> Therefore, this study evaluated the patterns of bone erosion, BME, synovitis, and tenosynovitis, and calculated the RA-MRI score (RAMRIS) of patients with RA at the carpal and metacarpophalangeal (MCP) joints using MRI. <h3>Methods</h3> MRI datasets from 43 RA patients were analyzed. All patients had undergone MRI of one wrist. In addition, 36 patients had MCP joint images taken, and 3 had also received MRI of the contralateral wrist and MCP joints. The MR images were evaluated for bone erosion, BME, and synovitis in consensus by 2 blinded readers according to the OMERACT RA-MRI score (RAMRIS). The MRI-detected tenosynovitis was evaluated based on Haavardsholm9s tenosynovitis score. <h3>Results</h3> The capitate, lunate, triquetrum, and hamate bones were the most common sites of erosion and BME and showed the highest RAMRIS erosion and BME scores. Moreover, MRI-detected tenosynovitis was present in 78.3% of all patients with RA, and the extensor compartment 4 and flexor digitorum profundus and superficialis were frequently affected. <h3>Conclusions</h3> This study identified the distribution and prevalence of MRI-detected bone erosion, BME, synovitis, and tenosynovitis of the wrist and MCP joints in RA patients. The patterns of the MRI-detected abnormalities may help to select sites for the application of MRI protocols in clinical trials and practice. <h3>References</h3> Ejbjerg B, McQueen F, Lassere M, Haavardsholm E, Conaghan P, O9Connor P, et al. The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint. Annals of the rheumatic diseases. 2005;64 Suppl 1:i23–47. Ostergaard M, Edmonds J, McQueen F, Peterfy C, Lassere M, Ejbjerg B, et al. An introduction to the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Annals of the rheumatic diseases. 2005;64 Suppl 1:i3–7. Conaghan P, Bird P, Ejbjerg B, O9Connor P, Peterfy C, McQueen F, et al. The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the metacarpophalangeal joints. Annals of the rheumatic diseases. 2005;64 Suppl 1:i11–21. Haavardsholm EA, Ostergaard M, Ejbjerg BJ, Kvan NP, Kvien TK. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Annals of the rheumatic diseases. 2007;66(9):1216–20. <h3>Acknowledgements</h3> The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. <h3>Disclosure of Interest</h3> None declared
THU0280 Comparison of classification criteria for sjÖgren's syndrome from 2002 and 2016 in an incident cohort diagnosed 2007 to 2011 from stockholm county sweden
Authors: M Kvarnström, M Wahren-Herlenius
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The current American-European Consensus Criteria (AECC) from 2002 has been the most widely used and applied all over the world. New classification criteria for Sjögren9s syndrome was published in 2016, designed in a collaboration between ACR and EULAR. They are made up of a scoring system in which 4 points are required for classification. The weight/score is as follows: Labial salivary gland biopsy with focal lymphocytic sialadenitis and focus score of ≥1 foci/4 mm<sup>2</sup> – 3 Anti-SSA/Ro positive – 3 Ocular Staining Score ≥5 (or van Bijsterveld score ≥4) in at least 1 eye – 1 Schirmer9s test ≤5 mm/5 minutes in at least 1 eye – 1 Unstimulated whole saliva flow rate ≤0.1 ml/minute – 1. <h3>Objectives</h3> Comparison of classification criteria for Sjögren9s syndrome from 2002 and 2016 in a 5 year cohort of incident patients diagnosed 2007 to 2011 from Karolinska University Hospital, Stockholm County, Sweden. We wanted to examine the consistency between the different classification criteria. <h3>Methods</h3> We compared a cohort of all diagnosed patients with primary Sjögren9s syndrome during the years 2007 to 2011 at the Dep. of Rheumatology at Karolinska University Hospital in Stockholm Sweden. Data on the item Ocular Staining Score ≥5 was not available since it is not included in AECC. The cohort consisted of 199 patients all fulfilling the 2002 AECC. Another eight patients did not fulfill the criteria but were regarded as possible Sjögren9s syndrome under development by the rheumatologist who investigated them. <h3>Results</h3> 196 of the 199 pSS patients also fulfilled the new criteria from 2016. The three patients who did not only had SSB autoantibodies and no positive biopsy. Of eight patients with suspicion of Sjögren9s syndrome under development, three fulfilled the new criteria. <h3>Conclusions</h3> The classification criteria for Sjögren9s syndrome from 2002 and 2016 are consistent. This study indicates a possibility that the new criteria may be more sensitive early in the disease development, as long as the classification is not based on autoantibody positivity against SSB. <h3>Disclosure of Interest</h3> None declared
SAT0481 The relationship between the patient acceptable symptom state (PASS) and disease activity in patients with psoriatic arthritis (PSA)
Authors: JZ Fei, A Perruccio, Y Ye, DD Gladman, V Chandran
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> PASS is the highest level of symptoms beyond which patients consider themselves well. Psoriatic Arthritis Disease Activity Score (PASDAS) is a recently developed composite disease activity measure that summarizes a patient9s disease in a single 0–10 score. <h3>Objectives</h3> In this study, we aimed to identify the PASDAS cut-off points for PASS, and to examine the agreement between PASS and the PASDAS thresholds for low (&lt;3.2), moderate (3.2–5.4), and high disease activity (&gt;5.4). <h3>Methods</h3> Patients were prospectively recruited from the University of Toronto PsA clinic. A standard protocol including physician assessment and patient-reported outcomes was used to record variables required to calculate PASDAS. In addition, each patient was asked to "think about all the ways your PsA has affected you during the last 48 hours. If you were to remain in the next few months as you were during the last 48 hours, would this be acceptable to you?" to assess PASS. For analysis, the PASDAS threshold for PASS was identified with the ROC analysis to maximize specificity and sensitivity. Furthermore, the agreement between PASS and low, moderate, and high PASDAS disease activity cut-offs were evaluated. <h3>Results</h3> 169 patients [61% male, mean age 56.1, mean disease duration 16.9 years, mean (SD) PASDAS 3.25 (1.1)] were recruited. The PASDAS threshold for the patient acceptable symptoms state (PASS+) was identified to be 3.84 (AUC – 0.88, sensitivity 0.82, specificity 0.94) using ROC curve analysis. 91% of patients with low disease activity (PASDAS &lt;3.2) considered their symptoms state acceptable (PASS+), and 100% of the patients with high disease activity (PASDAS &gt;5.4) considered their symptom state as unacceptable (PASS-). Furthermore, the mean (SD) PASDAS was 4.5 (1.0) in the PASS- group and 2.8 (1.1) in the PASS+ group. <h3>Conclusions</h3> The PASDAS threshold for patient acceptable symptoms state is 3.84, which is within the moderate disease activity range. Thus with a PASDAS of 3.84 or lower, PsA patients consider their symptom state acceptable for the next few months. This cut-off should be considered for shared decision making regarding treatments in PsA patients. <h3>Disclosure of Interest</h3> None declared
ACC/AHA/ACR/ASE/ASNC/HRS/NASCI/RSNA/SAIP/SCAI/ SCCT/SCMR/SIR 2008 Key Data Elements and Definitions for Cardiac Imaging
Authors: Robert C. Hendel, Matthew J. Budoff, John F. Cardella, Charles E. Chambers, John M. Dent, David M. Fitzgerald, John McB. Hodgson, Elizabeth Klodas, Christopher M. Kramer, Arthur E. Stillman, Peter L. Tilkemeier, R. Parker Ward, Wm. Guy Weigold, Richard D. White, Pamela K. Woodard
Journal: Circulation (2008)
Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease
Authors: Ian D. Pavord, Pascal Chanez, Gerard J. Criner, Huib A.M. Kerstjens, Stephanie Korn, Njira Lugogo, Jean-Benoit Martinot, Hironori Sagara, Frank C. Albers, Eric S. Bradford, Stephanie S. Harris, Bhabita Mayer, David B. Rubin, Steven W. Yancey, Frank C. Sciurba
Journal: New England Journal of Medicine (2017)

Patients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin-5.We performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy. In METREX, unselected patients in the modified intention-to-treat population with an eosinophilic phenotype were stratified according to blood eosinophil count (≥150 per cubic millimeter at screening or ≥300 per cubic millimeter during the previous year). In METREO, all patients had a blood eosinophil count of at least 150 per cubic millimeter at screening or at least 300 per cubic millimeter during the previous year. The primary end point was the annual rate of moderate or severe exacerbations. Safety was also assessed.In METREX, the mean annual rate of moderate or severe exacerbations in the modified intention-to-treat population with an eosinophilic phenotype (462 patients) was 1.40 per year in the mepolizumab group versus 1.71 per year in the placebo group (rate ratio, 0.82; 95% confidence interval [CI], 0.68 to 0.98; adjusted P=0.04); no significant between-group differences were found in the overall modified intention-to-treat population (836 patients) (rate ratio, 0.98; 95% CI, 0.85 to 1.12; adjusted P>0.99). In METREO, the mean annual rate of moderate or severe exacerbations was 1.19 per year in the 100-mg mepolizumab group, 1.27 per year in the 300-mg mepolizumab group, and 1.49 per year in the placebo group. The rate ratios for exacerbations in the 100-mg and 300-mg mepolizumab groups versus the placebo group were 0.80 (95% CI, 0.65 to 0.98; adjusted P=0.07) and 0.86 (95% CI, 0.70 to 1.05; adjusted P=0.14), respectively. A greater effect of mepolizumab, as compared with placebo, on the annual rate of moderate or severe exacerbations was found among patients with higher blood eosinophil counts at screening. The safety profile of mepolizumab was similar to that of placebo.Mepolizumab at a dose of 100 mg was associated with a lower annual rate of moderate or severe exacerbations than placebo among patients with COPD and an eosinophilic phenotype. This finding suggests that eosinophilic airway inflammation contributes to COPD exacerbations. (Funded by GlaxoSmithKline; METREX and METREO ClinicalTrials.gov numbers, NCT02105948 and NCT02105961 .).