tbuckley/cabot-search huggingface dataset:
A multicenter phase II study of bevacizumab (B) and temsirolimus (T) in women with recurrent epithelial ovarian cancer (OC): A study of the Mayo, Chicago, California, New York, Southeast, and Princess Margaret Phase II Consortia.
Authors: Robert Morgan, Amit M. Oza, Rui Qin, Briant Fruth, Hal Hirte, Helen Mackay, Daliah Tsoref, Elizabeth Laureen Strevel, Stephen Welch, Daniel Sullivan, Robert M. Wenham, Gini F. Fleming, Molly Brewer, Helen X. Chen, L. Austin Doyle, David R. Gandara, Joseph A. Sparano, Mark H. Einstein, Charles Erlichman
Journal: Journal of Clinical Oncology (2013)

5517 Background: Anti-angiogenic therapy is active in OC; the combination of VEGF and mTOR inhibitors is hypothesized to further improve activity. This report is the OC cohort of a multi-histology phase II study assessing the activity and toxicity of B/T. Methods: Patients (Pts) with recurrent epithelial OC who had received ≤ 2 chemotherapy regimens and no prior treatment with a VEGF or mTOR inhibitor were eligible. A two-stage design was used with second stage accrual if &gt;6 pts had objective responses (OR) or &gt;10 pts of the first 25 remained progression-free (PF) at six months (mo). Pre-defined end-points for a recommendation for further clinical trial evaluation included at least 15/50 with OR or 26/50 PF at six mo. Treatment included T 25 mg IV wkly and B 10 mg/kg IV q14 days on 28 day cycles. Results: 58 pts were enrolled (the first 50 pts are used to determine a final recommendation). Median age=62 (range 35-82). A median of 4 (range 1-23) cycles were administered. 24 were platinum-sensitive, 34 resistant. Off-study reasons included 13 adverse events and disease progression in 38. 3 refused further therapy due to toxicity. 14 of the first 50 pts had partial response (PR) (9 platinum-resistant); 25/50 remained PF (8 PR, 15 SD, 2 non-progressing) at 6 mo. Grade (gr) 3/4 toxicities occurring &gt;2 events include: fatigue (4), stomatitis (7), hypertension (5), neutropenia (4), thrombocytopenia (4), hypokalemia (3). One rectal and one vaginal fistula, and two colonic perforations (one gr 2 and one gr 3 during cycles 3 and 1 respectively) were observed. Episodes of gr 1/2 oral, nasal, pulmonary, vaginal and gastrointestinal hemorrhage were also observed. Conclusions: Although the OR and PFS did not reach pre-defined standards, the numbers of OR and 6 mo PFS suggest potential enhanced activity with a combination of mTOR inhibitor with anti-angiogenic therapy. Other combinations of these targeted agents may result in more satisfactory activity with less toxicity. N01-CM-62203 (PMH) N01-CM-62208 (Southeast Phase 2) N01 CM-62209 (CCCP) N01-CM-62204 (NYCC) N01-CM-2011-0071C (Chicago) N01-CM62205 (Mayo) Clinical trial information: NCT01010126.
Is Shouldice the best NON-MESH inguinal hernia repair technique? A systematic review and network metanalysis of randomized controlled trials comparing Shouldice and Desarda
Authors: Umberto Bracale, Paolo Melillo, Davide Piaggio, Leandro Pecchia, Diego Cuccurullo, Marco Milone, Giovanni Domenico De Palma, Giuseppe Cavallaro, Giampiero Campanelli, Giovanni Merola, Cesare Stabilini
Journal: International Journal of Surgery (2019)
PC<sub>20</sub> versus PD<sub>20</sub>: Why Change a Scientifically Well-Established and Clinically Relevant Test?
Authors: Israel Amirav, Michael T. Newhouse
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

In summary, RR measurement studies would benefit from an uncertainty (probabilistic) approach to the reference standard, including procedures to measure and reduce this uncertainty (5).Continuous RR measurements, rather than single-threshold values, should be used to assess clinical uncertainty and corrections considered for other known covariates such as core body temperature.
Authors’ reply to Skovenborg and Manfredini and colleagues
Authors: Zhilei Shan, Shilpa N Bhupathiraju
Journal: BMJ (2019)

We appreciate the thoughtful comments from Skovenborg and Manfredini and colleagues on our study about shift work, unhealthy lifestyle, and type 2 diabetes.11011

We did not include alcohol intake as a lifestyle factor, but we adjusted for categories of alcohol intake in our multivariable models. The inverse associations between alcohol consumption and risk of type 2 diabetes …
AB0531 Decision to initiate immunosuppression in patients with primary sjogren’s syndrome
Authors: S. Daia-Iliescu, C. Buzatu, T. Gudu, D. Zaharia, C. Purice, A. Borangiu, I. Saulescu, L. Groseanu, C. Constantinescu, M.M. Negru, V. Vlad, V. Bojinca, F. Berghea, A. Balanescu, D. Predeteanu, R. Ionescu, D. Opris-Belinski
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> There is limited data available (case series, small clinical trials and expert opinion) regarding the need to initiate immunosuppressive therapy in patients with primary Sjogren syndrome (pSS). <h3>Objectives</h3> The aim of this study is to determine the factors that correlate with physician's decision to start immunosuppressive therapy in pSS patients. <h3>Methods</h3> Subjects with pSS diagnosed according to the classification criteria in use at the time of their first presentation, were included in a monocentric cohort. A retrospective analysis was performed. The EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) at onset and Sjogren Syndrome Damage Index(SSDI) at the last evaluation were calculated. Treatment was given according to the physician's decision. Laboratory tests and Ultrasonography(US) of major salivary glands were performed in all cases. The data was analysed using Windows Excel/SPSS20.0. <h3>Results</h3> Corticotherapy was prescribed in 26/30 cases (86.6%), mean duration 50.65 months. Immunomodulatory treatment with hydroxychloroquine was given in 26/30 cases (86.6%). Immunosuppressive treatment was required in 10/30 patients (33.3%)- azathioprine 7 (23.3%) cases, methotrexate 3 (10%)cases. The mean ESSDAI score was 6.83±SD 1.8. In 19 (63.3%)cases disease activity was moderate or high (ESSDAI &gt;5). The mean damage score value (SSDI) was 3.1±SD1.2. There was a moderate correlation between the activity score ESSDAI and the damage score SDDI (r=0.41, p&lt;0,05). The physician's decision to start immunosuppression corelated significantly with the presence of hypergammaglobulinemia (r=0.4, p&lt;0,05). The duration of immunosuppressive treatment corelated moderately with specific Sjogren's US pattern of salivary glands (r=0.40, p&lt;0.05). In contrast, immunosuppressive treatment duration did not corelate with the activity and damage scores (ESSDAI and SSDI). <h3>Conclusions</h3> An important number of patients received corticotherapy, immunomodulatory agents and immunosuppressive therapy. The decision to initiate and maintain immunosuppressive therapy correlated with hypergammaglobulinemia and specific Sjogren's US changes. The damage score(SSDI) does not correlate with immunosuppressive therapy duration. <h3>References</h3> [1] Rischmueller M, Tieu J, Lester S. Primary Sjögren's syndrome. Best Pract Res Clin Rheumatol2016Feb 30. [2] Seror R, Bootsma H, Saraux A, et al. Defining disease activity states and clinically meaningful improvement in primary Sjögren's syndrome with EULAR primary Sjögren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann Rheum Dis2016. <h3>Disclosure of Interest</h3> None declared
Corrigendum re “Prospective Randomised Controlled Trial of Transobturator Tapes in Management of Urodynamic Stress Incontinence in Women: 3-Year Outcomes from the Evaluation of Transobturator Tapes Study” [Eur Urol 2012;62:843–51]
Authors: Mohamed Abdel-fattah, Alyaa Mostafa, Akinbowale Familusi, Ian Ramsay, James N’Dow
Journal: European Urology (2019)
Oral Gavage of Ginger Nanoparticle-Derived Lipid Vectors Carrying Dmt1 siRNA Blunts Iron Loading in Murine Hereditary Hemochromatosis
Authors: Xiaoyu Wang, Mingzhen Zhang, Shireen R.L. Flores, Regina R. Woloshun, Chunhua Yang, Liangjie Yin, Ping Xiang, Xiaodong Xu, Michael D. Garrick, Sadasivan Vidyasagar, Didier Merlin, James F. Collins
Journal: Molecular Therapy (2019)

Nanoparticles (NPs) have been utilized to deliver drugs to the intestinal epithelium in vivo. Moreover, NPs derived from edible plants are less toxic than synthetic NPs. Here, we utilized ginger NP-derived lipid vectors (GDLVs) in a proof-of-concept investigation to test the hypothesis that inhibiting expression of divalent metal-ion transporter 1 (Dmt1) would attenuate iron loading in a mouse model of hereditary hemochromatosis (HH). Initial experiments using duodenal epithelial organ cultures from intestine-specific Dmt1 knockout (KO) (Dmt1int/int) mice in the Ussing chamber established that Dmt1 is the only active iron importer during iron-deficiency anemia. Further, when Dmt1int/int mice were crossed with mice lacking the iron-regulatory hormone, hepcidin (Hepc−/−), iron loading was abolished. Hence, intestinal Dmt1 is required for the excessive iron absorption that typifies HH. Additional experiments established a protocol to produce GDLVs carrying functional Dmt1 small interfering RNAs (siRNAs) and to target these gene delivery vehicles to the duodenal epithelium in vivo (by incorporating folic acid [FA]). When FA-GDLVs carrying Dmt1 siRNA were administered to weanling Hepc−/− mice for 16 days, intestinal Dmt1 mRNA expression was attenuated and tissue iron accumulation was blunted. Oral delivery of functional siRNAs by FA-GDLVs is a suitable therapeutic approach to mitigate iron loading in murine HH.Graphical abstract
Abstract 16870: The Prognostic Impact of Appropriate Implantable Cardioverter Defibrillator Shock Based on Implant Indication: Insights From a Prospective, Population-based Registry in Ontario, Canada
Authors: Fahad Almehmadi, Andreu Porta-Sanchez, Hadas Fisher, Xuesong Wang, Andrew Ha, Peter C Austin, Douglas S Lee, Kumaraswamy Nanthakumar
Journal: Circulation (2016)

Introduction: There are compelling data on the negative impact of appropriate implantable cardioverter defibrillator (ICD) shock on survival based on trials data. It is not known if this increased ...
THU0194 Cd4+ t cells, immunoglobulins and risk of infection in patients with rheumatoid arthritis over multiple cycles of rituximab
Authors: F. Martins, A. Bensalem, T. Bejan-Angoulvant, A. Lhommas, J. Mélet, S. Mammou, G. Thibault, L. Bernard, P. Goupille, D. Mulleman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rituximab (RTX) may be responsible for infectious event in RA patients. Immunological markers may be associated with the occurrence of infections. <h3>Objectives</h3> To evaluate lymphocyte counts and immunoglobulin concentrations over multiple cycles of RTX in RA patients, and to analyse the relationship between these markers and the occurrence of infections. <h3>Methods</h3> Retrospective monocentric study on 94 RA patients treated with RTX. At baseline and during follow up, lymphocyte phenotyping (CD4+, CD3+, CD19 +cells), gammaglobulin, IgG, IgM and IgA concentration were assessed. Patients were dichotomized according to the absence or presence of infectious events. A student's test was used to compare the continuous variables and a Chi2 test or the Fisher test was used for the dichotomous variables. <h3>Results</h3> A total of 119 infectious events occurred during follow-up, of which only 11 were serious, with respective incidences of 65 per 100 patient-years and 6 per 100 patient-years. Low IgM concentration at RTX initiation and low IgG concentration (&lt;5 g/L) throughout follow-up were associated with an increased risk of infection. Both gammaglobulin and IgG concentrations decreased along with successive cycles of RTX in patients with infection, while they remained stable in patients without infection. Twelve patients had a CD4 +cell count&lt;200/mm<sup>3</sup> during follow up, of which one with a CD4 +cell count 233/mm<sup>3</sup> at baseline, who subsequently presented an opportunistic infection. <h3>Conclusions</h3> Gammaglobulin, IgM and IgG concentrations and CD4 +cell count are valuable before RTX initiation in RA patients. IgG or gammaglobulin concentration should also be monitored before each cycle. CD4 +lymphocytes monitoring should be considered in patients with low value at initiation. <h3>Disclosure of Interest</h3> F. Martins: None declared, A. Bensalem: None declared, T. Bejan-Angoulvant: None declared, A. Lhommas: None declared, J. Mélet: None declared, S. Mammou: None declared, G. Thibault: None declared, L. Bernard: None declared, P. Goupille Consultant for: Abbvie, Biogaran, BMS, Hospira, Janssen-Cilag, MSD, Pfizer, Sanofi-Genzyme and UCB, D. Mulleman Grant/research support from: Abbvie and Nordic Pharma, Consultant for: MSD, Novartis, UCB and Pfizer
Abstract 16339: Dose Dependent Effect of Caffeine on Adenosine Induced Myocardial Stress Perfusion by Rubidium-82 PET/CT
Authors: Christina Byrne, Andreas Kjaer, Mads Wissenberg, Preetee K Hurry, Philip Hasbak
Journal: Circulation (2017)

Introduction: Caffeine is a non-selective competitive antagonist of the A2A adenosine receptor that mediates coronary vasodilation. Studies show that caffeine may mask perfusion defects by inhibiti...
Risk Factors Associated With Accelerated Rubella IgG Antibody Loss in Previously Vaccinated, Treatment‐Naive Patients With Juvenile Systemic Lupus Erythematosus: A Prospective Study
Authors: Despoina N. Maritsi, Irene Eleftheriou, George Vartzelis, Nikos Spyridis, Maria N. Tsolia
Journal: Arthritis & Rheumatology (2019)
FRI0260 Polymorphisms of stat4 and mir146a predict the achievement of 5 years remission in patients with systemic lupus erythematosus
Authors: C. Perricone, C. Ciccacci, F. Ceccarelli, G. Mettola, I. Leccese, F.R. Spinelli, C. Alessandri, C. Politi, A. Latini, G. Novelli, G. Valesini, P. Borgiani, F. Conti
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex pathogenesis in which genes and environmental factors interact leading to a protean clinical picture. Treat-to-target recommendations have identified 'remission' as a target in SLE, since achievement of remission improves the outcome and is associated with decreased damage progression. Nonetheless, predicting factors for the achievement of remission are lacking. It is likely that genes associated with SLE pathogenesis may influence the disease course. <h3>Objectives</h3> Thus, our aim was to analyse previously identified loci associated with SLE in a cohort of SLE patients to evaluate their influence on remission achievement. <h3>Methods</h3> We recruited 117 Italian SLE patients. A panel of 34 SNPs in 19 genes involved in immune response, autophagy and inflammation, was selected. SNPs genotyping was performed by allelic discrimination assay by TaqMan assays (Applied Biosystems, Foster City, CA, USA) and ABI PRISM 7000. The main clinical/laboratory features (including injury index and disease activity) were collected on an electronic platform. Remission was defined according to Zen et al.<sup>1</sup> and evaluated over 5 years. A genotype/phenotype correlation analysis was performed. <h3>Results</h3> The variant alleles of rs7574965 (STAT4) (p&lt;0.001) and rs2910164 (MIR146a) (p=0.031) were significantly associated with lack of achievement of 5 years remission in SLE. Specifically, patients carrying the C allele of MIR146a were less likely to achieve 5 years remission (p=0.01, OR 0.235, 95% CI 0.074–0.752) as well as to achieve remission after 1, 2 and 3 years of evaluation (p=0.002, p=0.001, p=0.002, respectively). Among the clinical and laboratory features, 5 years remission was less likely to be achieved by patients who had arthritis in their clinical history (p=0.007), and who tested positive for anti-dsDNA (p=0.005). In a multinomial logistic regression analysis, arthritis (p=0.022, Exp(B)=0.255, 95% CI 0.079–0.820), anti-dsDNA (p=0.003, Exp(B)=0.166, 95% CI 0.051–0.537) and MIR146a rs2910164 gene variant (p=0.046, Exp(B)=0.250, 95% CI 0.064–0.974) were confirmed to be independent risk factors for unreached 5 years remission (table 1). <h3>Conclusions</h3> We describe for the first time the contribution of STAT4 and MIR146a SNPs as predicting factors for the achievement of 5 years remission in SLE. No genetic study has been performed so far in SLE, while a genetic profile of patients may be useful to predict the disease outcome. <h3>Reference</h3> [1] Zen, et al. Ann Rheum Dis. 2017Mar;76(3):562–565. <h3>Disclosure of Interest</h3> None declared
Risk factors for incident heart failure in age‐ and sex‐specific strata: a population‐based cohort using linked electronic health records
Authors: Alicia Uijl, Stefan Koudstaal, Kenan Direk, Spiros Denaxas, Rolf H. H. Groenwold, Amitava Banerjee, Arno W. Hoes, Harry Hemingway, Folkert W. Asselbergs
Journal: European Journal of Heart Failure (2019)

Aims Several risk factors for incident heart failure (HF) have been previously identified, however large electronic health records (EHR) datasets may provide the opportunity to examine the consistency of risk factors across different subgroups from the general population. Methods and results We used linked EHR data from 2000 to 2010 as part of the UK‐based CALIBER resource to select a cohort of 871 687 individuals 55 years or older and free of HF at baseline. The primary endpoint was the first record of HF from primary or secondary care. Cox proportional hazards analysis was used to estimate hazard ratios for associations between risk factors and incident HF, separately for men and women and by age category: 55–64, 65–74, and &gt; 75 years. During 5.8 years of median follow‐up, a total of 47 987 incident HF cases were recorded. Age, social deprivation, smoking, sedentary lifestyle, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, body mass index, haemoglobin, total white blood cell count and creatinine were associated with HF. Smoking, atrial fibrillation and diabetes showed stronger associations with incident HF in women compared to men. Conclusion We confirmed associations of several risk factors with HF in this large population‐based cohort across age and sex subgroups. Mainly modifiable risk factors and comorbidities are strongly associated with incident HF, highlighting the importance of preventive strategies targeting such risk factors for HF.
FRI0708-HPR The use of technology for symptom measurement in rheumatoid arthritis: a qualitative investigation
Authors: F. Matcham, R. Williams, E. Foncel, H.-Y. Tung, S. Norton, J. Galloway, M. Hotopf
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Rheumatoid Arthritis (RA) outcome measurement is limited by infrequent appointments, triggered by symptom flares, linking blood test data with retrospective recall of symptoms. Remote measurement technologies (RMT), such as wearable sensors or smartphone apps, provide opportunity for ongoing measurement of symptoms such as pain, fatigue, and depression, which may vary throughout the day, offering new insight into the lived experience of chronic illness [1]. However, implementation of such data collection strategies requires careful development with the service-user an integral part of co-design to maximise real-world acceptability [2]. <h3>Objectives:</h3> This study aimed to gather qualitative information about service-user priorities for using RMT for symptom measurement. <h3>Methods:</h3> Two focus groups were conducted in people with RA, using a semi-structured topic guide designed to elicit thoughts about RA symptoms considered important and acceptable for measurement via RMT. The focus groups were moderated by an expert service user (RW) and research lead (FM). A systematic thematic analysis was applied to the data, using a coding framework to extract themes and sub-themes by two researchers independently. <h3>Results:</h3> A total of 9 participants attended the two focus groups. Participants were aged 23–77 (mean=55.8, SD=18.1), with a mean disease duration of 20.2 (SD=15.2). All 9 were female, with 44.4% identifying as White British. Symptoms prioritisations and the perceived benefits and risks of technology were categorised into several themes including: personal empowerment; communication with healthcare teams; routine/convenience; and under-prioritised symptom experiences. <h3>Conclusions:</h3> The results of these focus groups highlight several areas to focus RMT development in this area, including identifying the symptoms patients feel are under-prioritised by healthcare providers, and establishing methods to ensure RMT can be embedded in daily activities despite fluctuating symptom severity. Future work testing specific app prototypes and wearable usability can ensure RMT projects are developed with optimised user experience. <h3>References</h3> 1. Lee YG, Jeong WS, Yoon G. Smartphone-based mobile health monitoring. Telemedicine and E-Health2012;18:585–90. 2. Grainger R, Townsley H, White B, Langlotz T, Taylor WJ. Apps for people with rheumatoid arthritis to monitor their disease activity: A review of app for best practice and quality. JMIR mHealth and uHealth2017;2:e7. <h3>Acknowledgements:</h3> We thank Radka Chura for her assistance with recruitment and all participants for their contribution. <h3>Disclosure of Interest:</h3> None declared