tbuckley/cabot-search huggingface dataset:
OP0230 Predictors of hypogammaglobulinemia during rituximab maintenance therapy in rheumatoid arthritis: a 12-year longitudinal multi-centre study
Authors: G Boleto, J. Avouac, J. Wipff, M. Forien, M. Dougados, C. Roux, A. Kahan, P. Dieudé, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rituximab (RTX) is an anti-CD20 monoclonal antibody that selectively depletes B-cell population. One of the drawbacks of a prolonged peripheral B-cell depletion is the suppression of protective antibodies and an increased risk for infectious events. However, few long-term data are available on predictors for the development of low levels of serum immunoglobulins in patients receiving repeated courses of RTX. <h3>Objectives</h3> We aimed at the identification of predictors for hypogammaglobulinemia occurrence in RA patients long-term treated with RTX in a 'real-life' setting. <h3>Methods</h3> Multicenter longitudinal observational usual care study including RA patients according to <sup><sup>ACR 1987</sup></sup> and/or ACR/<sup><sup>EULAR 2010</sup></sup> classification criteria followed and treated with RTX. A previous study assessing the safety profile of RTX in patients with RA reported a median follow-up of 30 months.<sup><sup>1</sup></sup> Therefore, we decided to include RA patients on RTX maintenance therapy, after a minimal exposition of 30 months. Serum protein electrophoresis was performed before each RTX infusion. Hypogammaglobulinemia and severe hypogammaglobulinemia were defined as total gammaglobulin &lt;6 g/L and &lt;4 g/L, respectively. Safety monitoring included the collection of all adverse events (AE) in particular severe infections. <h3>Results</h3> 134 patients met inclusion criteria: 113 female subjects (84.3%); mean age 52.1±11.4 years. Mean follow-up was 79.5±24.6 months and analysis was based on 854.9 patient-years (pt-yrs). Mean RTX cumulative dose was 12.0±4.9 g. Hypogammaglobulinemia (&lt;6 g/L) occurred during the follow-up period in 23 patients (2.7 events per 100 pt-yrs), leading to an incidence of 17.1%. The mean time to development of hypogammaglobulinemia was 64±23 months. A total of 9.7% of patients had severe infections (1.5 events per 100 pt-yrs). Patients who developed hypogammaglobulinemia were more likely to experience severe infections (26.1% vs 6.3%, p=0.033). Univariate Cox analysis identified age over 65 years (HR 4.28 [95% CI: 0.92 to 19.97], p&lt;0.001), low gammaglobulin levels prior the first RTX infusion (&lt;8 g/L) (HR 7.35 [95% CI: 1.82 to 29.68], p&lt;0.001) as predictors of protective factor (HR 0.26 [95% CI: 0.08 to 0.87], p=0.03). <h3>Conclusions</h3> Our results show that gammaglobulin levels of less than 8 g/L at baseline is a strong independent risk factor for developing subsequent hypogammaglobulinemia, whereas concomitant MTX therapy seems to be a protective factor in RA patients treated long-term with RTX. Identifying such predictors will raise clinicians' awareness and allow more tailored monitoring of RA patients long-term treated with RTX. <h3>Reference</h3> [1] Isvy, et al. Joint Bone Spine2012. <h3>Disclosure of Interest</h3> None declared
Novel Approaches to Acute Myeloid Leukemia Immunotherapy
Authors: Ofrat Beyar-Katz, Saar Gill
Journal: Clinical Cancer Research (2018)

Acute myeloid leukemia (AML) is a rapidly progressive, poor-prognosis malignancy arising from hematopoietic stem/progenitor cells. The long history of successful use of allogeneic hematopoietic cell transplantation (alloHCT) in AML indicates that this disease is immunoresponsive, leading to optimism that novel immunotherapies such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors will generate meaningful disease control. However, emerging data on the immunoevasive tactics employed by AML blasts at diagnosis and at relapse indicate that optimism must be tempered by an understanding of this essential paradox. Furthermore, AML has a low mutational burden, thus presenting few neoantigens for attack by autologous T cells, even after attempted reversal of inhibitory receptor/ligand interactions. In this review, we outline the known AML targets, explore immune evasion mechanisms, and describe recent data and current clinical trials of single and combination immunotherapies. Clin Cancer Res; 24(22); 5502-15. ©2018 AACR.
Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study)
Authors: Paul Didden, Agnes Reijm, Nicole Erler, Leonieke Wolters, Thjon Tang, Pieter ter Borg, Ivonne Leeuwenburgh, Marco Bruno, Manon Spaander
Journal: Endoscopy (2018)

Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis.In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first.Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs (P = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively (P = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events.Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia.
AB0676 Efficacy of rituximab therapy against anti-neutrophil cytoplasmic antibody-related hypertrophic pachymeningitis: a case series
Authors: K. Kobayashi, D. Nakagomi, S. Hanai, M. Yamagata, T. Sugiyama, H. Kawashima, M. Hiraguri, T. Kasuya, S. Furuta, K. Ikeda, H. Nakajima, K. Kitamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis presents with various symptoms. ANCA-associated hypertrophic pachymeningitis (HP) is a very rare pathology. <h3>Objectives</h3> This study aimed to investigate the efficacy of rituximab (RTX) against patients with ANCA-related HP. <h3>Methods</h3> Seven patients were identified by retrospective chart review from local registries at four Hospitals in Japan. All patients met Chapel Hill 2012 Consensus Conference definitions of ANCA–associated vasculitis and were complicated with HP. We assessed the dose of prednisolone, CRP, and MRI findings of HP before and after RTX administration. <h3>Results</h3> Three female and 4 male were evaluated. Median age was 66 years-old. Four cases had HP at the onset of vasculitis. Relapse of HP before RTX administration was found in 2 cases. RTX was used as an initial treatment in one patient. Daily dose of prednisolone and CRP were significantly decreased from baseline levels 24 weeks after RTX treatment. Evaluation of HP by contrast MRI showed improvement in six of seven cases. No relapse after RTX treatment was observed during the follow-up period of 24 weeks. Severe adverse effects were not found in any patients. <h3>Conclusions</h3> Our case series highlight the efficacy of RTX against patients with difficult-to-treat ANCA-related HP. Future studies in this context in a prospective manner are definitely required to establish the B-cell depletion therapy by RTX as a treatment option for ANCA-related HP. <h3>References</h3> [1] Shimojima Y, Kishida D, Hineno A, et al. Hypertrophic pachymeningitis is a characteristic manifestation of granulomatosis with polyangiitis: A retrospective study of anti-neutrophil cytoplasmic antibody-associated vasculitis. Int J Rheum Dis2017;20:489–496. [2] Aman S, Susheel K, Ajay W, et al. Successful treatment of hypertrophic pachymeningitis in refractory Wegener's granulomatosis with rituximab. Clin Rheumatol2010;29:107–110. <h3>Disclosure of Interest</h3> None declared
SP0041 Win session: what is new in the treatment of myositis?
Authors: H. Chinoy
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Much progress has been made over the last decade in the understanding of the inflammatory myopathies. It is heartening to see some of these developments now in clinical practice which is hopefully increasing the quality of care for myositis patients. This talk will summary the new upcoming treatments in myositis. However, treatment of a rare disease not only involves administering pharmacotherapeutic agents, but recognising when to treat and which poor prognostic groups required intensification. Antibody testing of the spectrum of newly identified myositis serology now allows for better stratification of patients and assists the physician with treatment, monitoring and prognosis. New EULAR/ACR criteria are available for classification to assist inclusion into clinical trials, as well as agreed definitions for minimal, moderate and major response. A better understanding of the pathogenesis has now led to randomised controlled trials now being conducted in the inflammatory myopathies, including targeting the innate immune pathway that will hopefully lead to a licensed treatment for this difficult orphan disease. <h3>Disclosure of Interest</h3> H. Chinoy Grant/research support from: UCB, Novartis, MedImmune – grant to University of Manchester, travel bursary – Abbvie, Janssen, Consultant for: Lilly, UCB, Janssen, Momenta, Novartis
FRI0490 Mortality and early severe infection in patients with anca-associated vasculitis
Authors: D. Waki, K. Nishimura, K. Kadoba, H. Mukoyama, R. Saito, T. Yokota
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The introduction of treatment regimens comprising of cyclophosphamide or rituximab combined with corticosteroids has brought about dramatic improvements in the prognosis of ANCA-associated vasculitis.<sup>1</sup> Severe infectious events, especially in the early phase of treatment, associated with risk of death have been reported in the past several studies.<sup>2,3</sup> <h3>Objectives</h3> We retrospectively investigated the association between mortality and early severe infection in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), and we also attempted to identify the potential predictors for early severe infection. <h3>Methods</h3> We recruited 182 consecutive hospitalised patients newly diagnosed with AAV at our hospital, from January 2000 to June 2017, in this retrospective cohort study. All cause mortality, relapse, and severe infections within six months after starting treatment (early severe infection) were analysed. <h3>Results</h3> The mean age was 70 years at diagnosis, and the classification according to the Chapel Hill Conference definition were microscopic polyangiitis (MPA) in 82 patients (45.1%), granulomatosis with polyangiitis (GPA) in 36 patients (19.8%), eosinophilic granulomatosis with polyangiitis (EGPA) in 24 patients (13.2%), and renal-limited vasculitis in 32 patients (17.6%).<sup>4</sup> Median follow up was 158 weeks (range 0–182 w). Using Cox regression analysis, elderly onset (age ≥75 years) AAV (p<i>=</i>0.027) and early severe infection (p<i>≤</i>0.001) were independent predictors of all cause mortality (table 1). Early severe infection tended to increase among patients who received immunosuppressive therapy of a corticosteroid combined with cyclophosphamide or rituximab (conventional treatment), and this trend was significant in non-severe (BVAS &lt;20) AAV patients (p<i>=</i>0.030) (table 2). Treatment response rate (p=0.058) and relapse rate (p<i>=</i>0.137) were not significant between the different treatment groups. <h3>Conclusions</h3> Early severe infection is an independent predictor of death in patients with AAV, and conventional treatment has a potential risk of death due to severe infection. This study supports the current EULAR recommendation that several treatment strategies are recommended according to the disease severity of vasculitis.<sup>5</sup> AAV patients who receive conventional treatment should be carefully monitored to reduce the occurrence of severe infection, especially in early phase of treatment. <h3>References</h3> [1] Little MA, et al. Ann Rheum Dis2010;69:1036–43. [2] Lai QY, et al. J Rheumatol2014;41(9):1849–55. [3] Solans-Laque R, et al. Medicine2017;96(8):e6083. [4] Janette JC, et al. Arthritis Rheum2013;65:1–11. [5] Yates M et al. Ann Rheum Dis 2016;75(9):1583–94. <h3>Disclosure of Interest</h3> None declared
Comparing the Efficacy of CBASP with Two Versions of CBT for Depression in a Routine Care Center: A Randomized Clinical Trial
Authors: Winfried Rief, Gabi Bleichhardt, Katharina Dannehl, Frank Euteneuer, Katrin Wambach
Journal: Psychotherapy and Psychosomatics (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The cognitive-behavioral analysis system of psychotherapy (CBASP) was developed for the treatment of chronic, early-onset depression. However, it is unclear whether this approach can be recommended for depression in general (episodic and chronic), and no direct comparisons between CBASP with different versions of cognitive-behavioral therapy (CBT) exist. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A randomized controlled trial compared 3 treatment conditions (all lasting 16 sessions) with a waiting list group (WL): CBASP, CBT with a focus on physical exercise (CBT-E), and CBT with a focus on pleasurable, low-energy and mindful activities (CBT-M). We included 173 patients and involved 41 therapists. Assessments were at baseline, after session 8, and at the end of treatment. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Our primary outcome Beck Depression Inventory-II indicated a general advantage of the CBT arms compared to CBASP [&lt;i&gt;F&lt;/i&gt;(6, 154.5) = 4.2, &lt;i&gt;p&lt;/i&gt; = 0.001], with significant contrasts in particular in favor of CBT-E. Effect sizes against WL were &lt;i&gt;d&lt;/i&gt; = 0.91 (CBT-E), 0.87 (CBT-M), and 0.47 (CBASP). A triple interaction with an additional factor “chronic versus episodic depression” [&lt;i&gt;F&lt;/i&gt;(6, 142.7) = 2.2, &lt;i&gt;p&lt;/i&gt; = 0.048] indicated that the treatments resulted in different outcomes, with best results again for CBT-E in particular in episodic depression. Responder rates indicated significant improvements (56% in both CBT arms, 34% in the CBASP arm, 3.4% in WL; intention-to-treat samples). As compared to CBASP, response rates were significantly higher for CBT-E (OR = 2.48; 95% CI = 1.02–6.00) and CBT-M (OR = 2.46; 95% CI = 1.01–6.01). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; CBASP was more effective than WL, but less effective than the 2 CBT arms. This was mainly caused by an advantage of CBT interventions in episodic depression.
Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial
Authors: L. Malorni, G. Curigliano, A.M. Minisini, S. Cinieri, C.A. Tondini, K. D’Hollander, G. Arpino, A. Bernardo, A. Martignetti, C. Criscitiello, F. Puglisi, M. Pestrin, G. Sanna, E. Moretti, E. Risi, C. Biagioni, A. McCartney, L. Boni, M. Buyse, I. Migliaccio, L. Biganzoli, A. Di Leo
Journal: Annals of Oncology (2018)

The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pretreated patients. Preclinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multicenter study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in postmenopausal women with moderately pretreated, estrogen receptor-positive, HER2 negative advanced breast cancer.Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1 : 1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary end point was clinical benefit rate (CBR); secondary end points included progression-free survival (PFS).Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% [95% confidence interval (CI): 41.5-63.7] for combination therapy, and 60% (95% CI: 47.8-72.9) for monotherapy. Median PFS was 10.8 months (95% CI: 5.6-12.7) for combination therapy, and 6.5 months (95% CI: 5.4-8.5) for monotherapy [hazard ratio (HR) 0.69; 95% CI: 0.4-1.1, exploratory P-value = 0.12]. Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI: 0.3-0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months.Palbociclib has clinical activity as a single agent in women with moderately pretreated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET.NCT02549430.
Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion
Authors: Yogesh Bhattarai, Brianna B. Williams, Eric J. Battaglioli, Weston R. Whitaker, Lisa Till, Madhusudan Grover, David R. Linden, Yasutada Akiba, Karunya K. Kandimalla, Nicholas C. Zachos, Jonathan D. Kaunitz, Justin L. Sonnenburg, Michael A. Fischbach, Gianrico Farrugia, Purna C. Kashyap
Journal: Cell Host & Microbe (2018)
Srsf2 P95H initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells
Authors: Monique F. Smeets, Shuh Ying Tan, Jane Jialu Xu, Govardhan Anande, Ashwin Unnikrishnan, Alistair M. Chalk, Scott R. Taylor, John E. Pimanda, Meaghan Wall, Louise E. Purton, Carl R. Walkley
Journal: Blood (2018)
Is the time right for quantitative public health guidelines on sitting? A narrative review of sedentary behaviour research paradigms and findings
Authors: Emmanuel Stamatakis, Ulf Ekelund, Ding Ding, Mark Hamer, Adrian E Bauman, I-Min Lee
Journal: British Journal of Sports Medicine (2018)

Sedentary behaviour (SB) has been proposed as an 'independent' risk factor for chronic disease risk, attracting much research and media attention. Many countries have included generic, non-quantitative reductions in SB in their public health guidelines and calls for quantitative SB targets are increasing. The aim of this narrative review is to critically evaluate key evidence areas relating to the development of guidance on sitting for adults. We carried out a non-systematic narrative evidence synthesis across seven key areas: (1) definition of SB, (2) independence of sitting from physical activity, (3) use of television viewing as a proxy of sitting, (4) interpretation of SB evidence, (5) evidence on 'sedentary breaks', (6) evidence on objectively measured sedentary SB and mortality and (7) dose response of sitting and mortality/cardiovascular disease. Despite research progress, we still know little about the independent detrimental health effects of sitting, and the possibility that sitting is mostly the inverse of physical activity remains. Unresolved issues include an unclear definition, inconsistencies between mechanistic and epidemiological studies, over-reliance on surrogate outcomes, a very weak epidemiological evidence base to support the inclusion of 'sedentary breaks' in guidelines, reliance on self-reported sitting measures, and misinterpretation of data whereby methodologically inconsistent associations are claimed to be strong evidence. In conclusion, public health guidance requires a consistent evidence base but this is lacking for SB. The development of quantitative SB guidance, using an underdeveloped evidence base, is premature; any further recommendations for sedentary behaviour require development of the evidence base and refinement of the research paradigms used in the field.
Margaret McCartney: Getting the abstract in perspective
Authors: Margaret McCartney
Journal: BMJ (2018)

There’s a conference on! Who could have guessed? On 1 June we had the front page headline, “Cancer blood test hailed as ‘holy grail.’”1 On 2 June we had, “NHS cancer patients ‘failing to be correctly monitored.’”2 On 3 June, joy of joys: “GPs handing out too many antibiotics harms cancer survival chances.”3 In case that last one hasn’t treated my colleagues’ hypotension enough, here’s a choice quote: “People see their GP and the GP thinks, ‘Oh my goodness it’s a cancer patient, they need antibiotics.’”3

Let us regroup. This is a meeting of the American Society of Clinical Oncology (ASCO), where research is transmitted to the world through press briefings, abstracts, and talks. We …
Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial
Authors: Eric S Daar, Edwin DeJesus, Peter Ruane, Gordon Crofoot, Godson Oguchi, Catherine Creticos, Jürgen K Rockstroh, Jean-Michel Molina, Ellen Koenig, Ya-Pei Liu, Joseph Custodio, Kristen Andreatta, Hiba Graham, Andrew Cheng, Hal Martin, Erin Quirk
Journal: The Lancet HIV (2018)