tbuckley/cabot-search huggingface dataset:
Cytotoxic T Cells and their Activation Status are Independent Prognostic Markers in Meningiomas
Authors: Carmen Rapp, Steffen Dettling, Fang Liu, Anna Theresa Ull, Rolf Warta, Christine Jungk, Saskia Roesch, Andreas Mock, Felix Sahm, Melissa Schmidt, Gerhard Jungwirth, Klaus Zweckberger, Katrin Lamszus, Konstaninos Gousias, Almuth F. Kessler, Niels Grabe, Mario Loehr, Ralf Ketter, Steffi Urbschat, Christian Senft, Manfred Westphal, Amir Abdollahi, Juergen Debus, Andreas von Deimling, Andreas Unterberg, Matthias Simon, Christel C. Herold-Mende
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Clinically aggressive meningiomas (MGMs) are rare but treatment-resistant tumors in need for more effective therapies. Because tumor-infiltrating T lymphocytes (TILs) are essential for successful immunotherapy, we assessed TIL numbers and their activation status in primary (p-) and recurrent (r-) meningiomas and their impact on survival. Experimental Design: Presence of TILs was analyzed in 202 clinically well-annotated cases (n = 123 pMGMs and n = 79 rMGMs) focusing on higher-grade meningiomas [n = 97 World Health Organization (WHO) °II, n = 62 WHO°III]. TILs were quantified by a semiautomated analysis on whole-tissue sections stained by multicolor immunofluorescence for CD3, CD8, FOXP3, and programmed cell death protein 1 (PD-1). Results: Median T-cell infiltration accounted for 0.59% TILs per total cell count. Although there were no significant WHO°-dependent changes regarding helper (CD3+CD8−FOXP3−) and cytotoxic (CD3+CD8+FOXP3−) TILs in pMGMs, higher number of cytotoxic TILs were associated with an improved progression-free survival (PFS) independent of prognostic confounders. rMGMs were characterized by lower numbers of TILs in general, helper, and cytotoxic TILs. The additional analysis of their activation status revealed that a proportion of PD-1+CD8+ TILs within the TIL population was significantly decreased with higher WHO grade and in rMGMs. Furthermore, lower proportions of PD-1+CD8+ TILs were associated with inferior PFS in multivariate analyses, arguing for PD-1 as activation rather than exhaustion marker. Conclusions: We identified higher numbers of CD3+CD8+FOXP3− TILs and proportions of PD-1–expressing CD3+CD8+FOXP3− TILs as novel biomarkers for better survival. These findings might facilitate the selection of patients who may benefit from immunotherapy and argue in favor of an intervention in primary rather than recurrent tumors.
Alemtuzumab for Immune-Related Myocarditis Due to PD-1 Therapy
Authors: Khashayar Esfahani, Najwa Buhlaiga, Paméla Thébault, Réjean Lapointe, Nathalie A Johnson, Wilson H Miller
Journal: New England Journal of Medicine (2019)

Alemtuzumab for Immune-Related Myocarditis Myocarditis after the use of immune checkpoint inhibitors is a potentially fatal complication. Immune suppression with glucocorticoids is often effective ...
AB0697 LOW DOSE CYCLOPHOSPHAMIDE AND PIRFENIDONE MIGHT WORK IN SYNERGY TO RELIEVE INTERSTITIAL LUNG DISEASE WITH CONNECTIVE TISSUE DISEASE: A PRELIMINARY OBSERVATIONAL STUDY
Authors: Qingran Yan, Lichong Shen, Xiaoxiang Chen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> There are anti-inflammation and anti-fibrosis agents available for connective tissue disease associated interstitial lung disease (CTD-ILD). A clinical study has been initiated to assess the combination of the two (NCT03221257), but whether they can spare dose for each other is unknown. <h3>Objectives</h3> This preliminary study is aimed to observe outcomes of CTD-ILD patients receiving cyclophosphamide plus pirfenidone as a rescue therapy, with each agent at about one third of routine dosage. <h3>Methods</h3> We enrolled CTD-ILD patients who did not improve their symptoms (dyspnea or cough) after at least one-month steroids treatment (prednisone≥1mg/kg daily). Patients who had adjusted immunosuppressive agents other than steroids or had received anti-fibrotic medications within three months before enrollment were ruled out. We switched the treatment into pulse cyclophosphamide (0.4g/m2 monthly) combined with pirfenidone (300mg twice per day). Besides, we reduced the steroids to prednisone 0.5mg/kg daily and then tapered routinely. All the patients were followed up for 12 months. <h3>Results</h3> We enrolled seven patients, of whom two had anti-synthetase syndrome, two had Sjögren syndrome, two had scleroderma and one had mixed connective tissue disease. The media DLCO was 51% of prediction (range47.7% to 63%) and media FVC was 72.3% of prediction (range 39% to 81%). The media 6MWD was 275m (range202 to 324m). At the end of 12-month follow-up, all the patients regained functional independence with a media 52.7% increase of 6-minute walk distance (range34.4% - 86.3%). Pulmonary function tests showed improved forced vital capacity (median improvement 13.4%, range 0-35.9%) and DLCO (median improvement 6.3%, range 1.7%-16%). The HRCT score had a median decrease of 20.1% (range 11.7% to 29.6%). For quality of life assessment, the SGRQ total score had a median improvement of 53.3% (range 19.5% to 61.7%). Of note, no adverse events were observed during the 12-month follow-up. <h3>Conclusion</h3> Our Study provided preliminary but promising clinical evidence for a new strategy in treating CTD-ILD, that cyclophosphamide and pirfenidone might work in synergy and spare dose for each other. A well-designed controlled study is needed to further establish its safety and efficacy. <h3>References</h3> None. <h3>Disclosure of interests</h3> None declared
Letter to the editor: Chlamydia trachomatis samples testing falsely negative in the Aptima Combo 2 test in Finland, 2019
Authors: Magnus Unemo, Damon Getman, Ronza Hadad, Michelle Cole, Nicholas Thomson, Mirja Puolakkainen, Gianfranco Spiteri
Journal: Eurosurveillance (2019)

Preview this article: Letter to the editor: Chlamydia trachomatis samples testing falsely negative in the Aptima Combo 2 test in Finland, 2019, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/24/eurosurv-24-24-4-1.gif
PS949 INOTUZUMAB OZOGAMICIN (INO) TREATMENT IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA (R/R ALL): OUTCOMES OF PATIENTS TREATED IN SALVAGE ONE WITH A LONG DURATION OF FIRST REMISSION
Authors: M. Stelljes, E. Jabbour, A. Advani, D.J. DeAngelo, D.I. Marks, W. Stock, S. O’Brien, R.D. Cassaday, T. Wang, A. Neuhof, E. Vandendries, H. Kantarjian
Journal: HemaSphere (2019)

Background: In R/R ALL, data are limited supporting targeted therapies like InO as first salvage in patients (pts) who achieved a long duration of first complete remission (CR1). InO, a calicheamicin‐conjugated antibody, targets CD22 on ALL blasts. Aims: Here we report outcomes in pts with ALL in first salvage (S1) who had a long CR1 before receiving InO vs standard of care chemotherapy (SC). image Methods: Adults with CD22+ R/R ALL, stratified by salvage and length of remission (CR1 ≥ or &lt;12 mos), were randomized to receive InO (n = 164) or SC (n = 162). Methods were previously described (Kantarjian et al, NEJM 2016), with data shown up to the last patient last visit (January 4, 2017). Outcomes including complete remission (CR)/CR with incomplete hematologic recovery (CRi) and overall survival (OS) were determined for S1 pts who achieved CR1 ≥ 12 mos and CR1 ≥ 18 mos. Results: For S1 pts with CR1 ≥ 12 mos or CR1 ≥ 18 mos, InO and SC arms had generally comparable baseline characteristics. For S1 pts with CR1 ≥ 12 mos and CR1 ≥ 18 mos, fewer pts had received a prior stem cell transplant in the InO vs SC arm (10.4% vs 25.0% and 9.7% vs 21.4%). For S1 pts with CR1 ≥ 12 mos and CR1 ≥ 18 mos respectively, InO vs SC treatment led to a higher CR/CRi rate (85.4% vs 27.5% [ P &lt; 0.0001] and 83.9% vs 32.1% [ P &lt; 0.0001]) and improved OS (HR = 0.547 [ P = 0.0086] and 0.504 [ P = 0.0163]), with veno‐occlusive liver disease reported in 12.5% and 12.9% of InO pts. Summary/Conclusion: Improved outcomes were seen with InO vs SC among S1 pts who had a long first complete remission (CR1 ≥ 12 mos or CR1 ≥ 18 mos), supporting the benefit of InO vs SC in this population.
Abstract 15875: Zebrafish as a High-Throughput System for Long QT Syndrome
Authors: Chuanchau J Jou, Rachelle K Smith, Martin Tristani-Firouzi
Journal: Circulation (2011)

Introduction: Since the advent of commercial Long QT Syndrome (LQTS) screening, majority of novel hERG (KCNH2) mutations are not functionally characterized. A high-throughput system for functional ...
SILK studies — capturing the turnover of proteins linked to neurodegenerative diseases
Authors: Ross W. Paterson, Audrey Gabelle, Brendan P. Lucey, Nicolas R. Barthélemy, Claire A. Leckey, Christophe Hirtz, Sylvain Lehmann, Chihiro Sato, Bruce W. Patterson, Tim West, Kevin Yarasheski, Jonathan D. Rohrer, Norelle C. Wildburger, Jonathan M. Schott, Celeste M. Karch, Selina Wray, Timothy M. Miller, Donald L. Elbert, Henrik Zetterberg, Nick C. Fox, Randall J. Bateman
Journal: Nature Reviews Neurology (2019)
Letter to the Editor: Hepatocellular Carcinoma Surveillance in High‐Risk Patients With Cirrhosis: Contrast‐Enhanced Ultrasound May Be a Choice
Authors: Jiangfa Li, Jiming Wang, Shuiping Yu, Guandou Yuan, Songqing He
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the study by Kim et al.,1 who compare the cost‐effectiveness of semi‐annual surveillance using magnetic resonance imaging (MRI) versus ultrasonography (US) in patients with compensated cirrhosis. The results showed that semiannual surveillance using liver‐specific contrast‐enhanced MRI may be more cost‐effective than US in patients with virus‐associated compensated cirrhosis at sufficiently high hepatocellular carcinoma (HCC) risk, despite the higher test cost of MRI. We completely agree with these valuable and interesting findings. After reading the article carefully, some issues may need to be discussed. This study compared the detection sensitivity of MRI with liver‐specific contrast with US for early‐stage HCC in patients with compensated cirrhosis and incremental cost‐effectiveness ratio for these patients. Although the single‐item price of MRI with liver‐specific contrast is significantly higher than that of US, the diagnostic accuracy of MRI for early‐stage HCC is also significantly higher than that of US.1 MRI with liver‐specific contrast can detect smaller HCC lesions, which is beneficial to early treatment, improve prognosis, and prolong life expectancy.3 However, the sensitivity and specificity of contrast‐enhanced US (CEUS), which is also recommended by various HCC guidelines for surveillance, for the detection of HCC was much higher than that of regular US. CEUS has similar diagnostic performance for detection of liver lesions to that of liver‐specific contrast‐enhanced MRI, but the price is significantly lower than that of MRI.4 In addition, CEUS has many other advantages, such as high temporal and spatial resolution, high patient tolerance, the ability to perform multiple contrast injections over a short interval, and the ability to perform at bedside.5 Taken together, CEUS could also be a good surveillance option for patients with compensated cirrhosis at high risk of HCC.
Remember Me? The Bone Marrow in Pulmonary Fibrosis
Authors: Sunad Rangarajan, Victor J. Thannickal
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

s population lives in areas that exceed the current ozone standard (6).As healthcare providers and scientists, the members of the American Thoracic Society should urge the EPA to carefully consider the increasingly strong epidemiologic evidence that long-term exposure increases the risk of cardiopulmonary mortality when the agency next evaluates the current NAAQS for ozone.
Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence
Authors: Jakob M. Goldmann, Vladimir B. Seplyarskiy, Wendy S. W. Wong, Thierry Vilboux, Pieter B. Neerincx, Dale L. Bodian, Benjamin D. Solomon, Joris A. Veltman, John F. Deeken, Christian Gilissen, John E. Niederhuber
Journal: Nature Genetics (2018)
Abstract 18639: Protective Function of MiRNA-495 in Cardiomyocyte Ischemia-Reperfusion Injury Through Apoptosis Regulation
Authors: Zaman Afrasiabi, Michael A Kuliszewski, Pratiek N Matkar, Hao H Chen, Howard Leong-Poi
Journal: Circulation (2017)

Introduction: Noncoding RNAs have emerged as important regulators of cardiac development and cardiovascular diseases. The Runt-related transcription factor 3 (RUNX3) is downregulated in cancer cell...
UGT1A1 Polymorphism and Mortality Outcome after Allogeneic Stem Cell Transplantation with Busulfan Based Regimen
Authors: Patrizia Chiusolo, Angelo Minucci, Metafuni Elisabetta, Sabrina Giammarco, Monica Rossi, Gessica Minnella, Cecilia Zuppi, Andrea Urbani, Andrea Bacigalupo, Ettore Capoluongo, Simona Sica
Journal: Blood (2017)
FRI0501 EVALUATION OF BONE QUALITY BY TRABECULAR BONE SCORE (TBS) IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS
Authors: Andrea Casabella, Sabrina Paolino, Elisa Alessandri, Vanessa Smith, Barbara Ruaro, Carmen Pizzorni, Alberto Sulli, Maurizio Cutolo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic lupus erythematosus (SLE) patients shown an increased risk of low bone mass as a result of multifactorial events: physical inactivity, persistent inflammation, low vitamin D levels (photosensitivity) and glucocorticoid treatment. Trabecular Bone Score (TBS), is an index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get information about bone quality in several rheumatic diseases (1-4). <h3>Objectives</h3> The aims of this study were to examine the prevalence and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in female patients affected by SLE and to compare with matched healthy subjects (CNT). <h3>Methods</h3> 40 female patients (mean age 47±14 years) affected by SLE and 40 age- matched CNT (mean age 49±8 years) were enrolled. Bone Mineral Density (BMD, g/cm<sup>2</sup>) of the lumbar spine (L1-L4) was analyzed using a DXA scan (GE, Lunar Prodigy) Lumbar spine TBS was derived for each spine DXA examination using the TBS index (TBS iNsight Medimaps). <h3>Results</h3> The mean BMD±SD was 0.85±0.22 g/cm<sup>2</sup> at the lumbar spine and 0.64 ± 0.32 g/cm<sup>2</sup> at the hip in SLE patients. The prevalence of osteopenia was 39.0% and 16.4% of osteoporosis in SLE patients. Most of SLE patients (70%) presented a bone loss that was significantly lower when compared with control group (p&lt;0.001). Likewise, lumbar spine TBS score was found significantly lower in SLE patients compared with CNT (0.868±0.227 vs 1.482±0.113,p&lt;0.001, respectively). An history of high-dose oral glucocorticoids (&gt; 10 mg/day) was associated with the preservation of BMD at the lumbar spine but not in spinal trabecular bone as observed by TBS analysis. <h3>Conclusion</h3> SLE is associated with significant trabecular bone loss, which could not be caused by glucocorticoid therapy. This study confirms the role of TBS as new and safe diagnostic tool for the quantification of the bone quality in chronic and systemic inflammatory rheumatic diseases, such as SLE. <h3>References</h3> [1] Cutolo M, et al. Ann Rheum Dis.2009;68 446-7; 2 Dey M, et al. Lupus. 018;271547-1551; 3 Ruaro B, Casabella A,et al. Rheumatology (Oxford). 2018;57:1548-1554. 4 Ruaro B, Casabella A,et al. Clin Rheumatol. 2018Nov;37(11):3057-3062. <h3>Disclosure of Interests</h3> None declared
PB2127 BORTEZOMIB-HIGH DOSE METHYLPREDNISOLONE OFFERS IMPROVED HAEMATOLOGICAL RESPONSES AND OVERALL SURVIVAL COMPARED TO BORTEZOMIB-DEXAMETHASONE IN SYSTEMIC LIGHT CHAIN AMYLOIDOSIS
Authors: A. S. Mahmood, S. Sachchithanantham, S. Harrison, R. Manwani, F. Sharpley, C. Quarta, T. Rezk, A. Martinez De Azcona Naharro, K. Yong, N. Rabin, R. Popat, C. Kyriacou, X. Papanikolaou, S. D'Sa, H. Lachmann, C. Whelan, J. Gillmore, M. Fontana, P. Hawkins, A. Wechalekar
Journal: HemaSphere (2019)

Background: Bortezomib based regimes have become the standard of care for front line treatment of systemic AL amyloidosis. Rapidity of response is one of the key factors in determining survival–patients achieving deeper responses have significantly better outcomes. Most patients are treated with cyclophosphamide (or melphalan)-bortezomib-dexamethasone based on previous reports from our and other centres. Dexamethasone, a key component of the regime, has significant toxicity and the long half-life predisposes to fluid retention. Aims: We report the use of high dose methylprednisolone as an alternative to high dose dexamethasone with better responses, survival and tolerance. Methods We report matched outcomes (matched for Mayo cardiac stage, presenting serum free light chains and use of doxycycline) of two cohorts of 26 patients each with systemic AL patients treated with weekly Velcade plus Methylprednisolone and Velcade plus Dexamethasone (+Cyclophosphamide or Thalidomide in each case) respectively. Both cohorts received oral doxycycline 100 mg BD. The doses of dexamethasone were 20-40 mg weekly orally compared to those of methylprednisolone 500-750 mg intravenously weekly. The FLC measurements were monitored monthly to assessment ongoing treatment response. Results: The median age in both groups were 69.2 and 67.3 years, all having cardiac involvement (Mayo stage 2 in 3 patients; 11.6%, Mayo stage 3A in 15 patients; 57.7%, Mayo stage 3B in 8 patients; 30.7%) in both groups and renal involvement in 50.0% and 69.2% in the Methylprednisolone and Dexamethasone cohorts respectively. Haematological responses at 1 month/2 months were as follows: CR: 11.5% and 7.7%/26.9% and 19.2, VGPR 0 and 7.7%/7.7% and 0, PR 38.5% and 30.8%/42.3% and 50%, in the Methylprednisolone and Dexamethasone groups: respectively. The median survival was not reached in the Methylprednisolone cohort and was 21.6 months in the Dexamethasone cohort. The 2 year OS in the Methylprednisolone and Dexamethasone groups were 65.4% and 43.1% with 12 and 14 deaths respectively. Methylprednislolone appeared to be better tolerated with less fluid overload and hospital admissions. Summary/Conclusion: Bortezomib based regimes with either Methylprednisolone and Dexamethasone achieve excellent good haematological responses. However, the Methylprednisolone cohort showed faster haematological responses which translated into an improved OS in comparison to the Dexamethasone cohort. This preliminary data suggests that a review of dexamethasone in AL amyloidosis with alternatives should be considered in further prospective studies.
Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination
Authors: Lisa C. Lindesmith, Jonathan R. McDaniel, Anita Changela, Raffaello Verardi, Scott A. Kerr, Veronica Costantini, Paul D. Brewer-Jensen, Michael L. Mallory, William N. Voss, Daniel R. Boutz, John J. Blazeck, Gregory C. Ippolito, Jan Vinje, Peter D. Kwong, George Georgiou, Ralph S. Baric
Journal: Immunity (2019)

Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire—pre- and post-vaccination—and select several antibody clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen.
AB0682 CIRCULATING FIBROCYTES IN LIMITED CUTANEOUS SYSTEMIC SCLEROSIS PATIENTS: CORRELATION WITH DERMAL THICKNESS
Authors: Barbara Ruaro, Stefano Soldano, Vanessa Smith, Sabrina Paolino, Carmen Pizzorni, Paola Contini, Paola Montagna, Samuele Tardito, Maurizio Cutolo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is characterized by early skin impairment (1,2) and the modified Rodnan skin score (mRSS) is the validated method to assess the severity of this impairment. Whilst skin high frequency ultrasound (US) is a relatively new technique to measure dermal thickness (DT) (2-4). Recent findings have reported the important contribution circulating fibrocytes make in the early stage of dermal repair and fibrosis. Indeed, as fibrocytes may be an important source of activated fibroblasts/myofibroblasts, it is reasonable to presume that they could be responsible for the increase in these cells observed in the tissue of SSc patients (5-7). <h3>Objectives</h3> The aim of this study was to identify any correlation between the modified Rodnan skin score (mRSS), dermal thickness (DT), measured by skin high frequency ultrasound (US) and the percentage of circulating fibrocytes in patients with limited cutaneous systemic sclerosis (lcSSc). <h3>Methods</h3> After obtaining approval and written informed consent and the Ethics Committee approval 8 lcSSc patients (7 females, 1 male) and 5 (4 females, 1 male) age-matched healthy volunteers (CNT) were enrolled. The lcSSc patients fulfilled the 2013 aCR/EULAR criteria for SSc (8). DT was evaluated by both mRSS and US (18 and 22 MHz probes), in all SSc patients and CNT, in the standard 17 skin areas evaluated by mRSS. The percentage of circulating fibrocytes was obtained by isolating them from the peripheral blood mononuclear cells (PBMCs) in all lcSSc patients and CNTs. Non-parametric tests were used for the statistical analysis. <h3>Results</h3> The percentage of circulating fibrocytes was positively correlated with DT-US, evaluated by the 22 MHz and the 18 MHz probes (p=0.04 and p=0.03, respectively) and mRSS (p=0.04) in lcSSc patients. Conversely, there was no correlation between these parameters in the CNT group (p&gt;0.05). <h3>Conclusion</h3> The study demonstrates a significant relationship between DT, evaluated by both mRSS and US and the percentage of circulating fibrocytes in lcSSc patients. This observation may well support the hypothesis that circulating fibrocytes make a crucial contribution to skin fibrosis progression. <h3>References</h3> [1] Cutolo M, et al. Best Pract Res Clin Rheumatol. 2016;30:670-87. 2. Krieg T, et al. Rheumatology 2009;48:iii14-8. 3. Clements PJ, et al. J Rheumatol 1995;22:1281-5. 4. Ruaro B, et al. Arthritis Rheumatol 2015; 67 (suppl 10). 5. Cutolo M, et al. Arthritis Res ther. 2018;20:157. 6. Brunasso aM, et al. F1000Res. 2016 apr 22;5. doi: 10.12688/f1000research.7986.1. 7. Reilkoff R, et al. Nat Rev Immunol. 2011;11:427-35. 8. van den Hoogen F, et al. Ann Rheum Dis. 2013;72:1745-55. <h3>Disclosure of interests</h3> None declared