tbuckley/cabot-search huggingface dataset:
Combination Cancer Immunotherapy with Molecular Targeted Agents/Anti-CTLA-4 Antibody for Hepatocellular Carcinoma
Authors: Masatoshi Kudo
Journal: Liver Cancer (2019)

The recent development of immunotherapy has advanced the treatment of various cancers. The anti-PD-1 antibody nivolumab was designated by the FDA as a breakthrough therapy in September 2014. Subsequently, the anti-PD-1 antibody pembrolizumab received the same designation. Nivolumab is currently approved as a drug with good efficacy against a range of specific malignancies including malignant melanoma, non-small cell lung cancer, kidney cancer, stomach cancer, Hodgkin's lymphoma, and urothelial carcinoma. In addition, it is being investigated for the treatment of other types of cancer in promising clinical studies. Pembrolizumab was also approved by the FDA for similar indications in addition to the microsatellite instability-high or mismatch repair-deficient solid tumors.






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Prof. M. Kudo Editor Liver Cancer
FRI0105 Concomitant use of corticosteroids at the baseline does not affect the drug survival of abatacept in rheumatoid arthritis
Authors: S.S. KOCA, B. Öz, A. Karatas, H.E. Dalkılıç, G. Can, Y. Pehlivan, S. Senel, A. Yazıcı, N. İnanç, A. Çefle, Z. Ertürk, S. Akar, B. Yagiz, B. Göker, A.M. Birlik, F. Önen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to deformities and disabilities. in the treatment of RA glucocorticoids are selected sometimes to relief symptoms and to increase compliance for treatment. <h3>Objectives</h3> The purpose of our study is to investigate whether concomitant glucocorticoid treatment at the baseline affects drug survival for abatacept treatment in RA. <h3>Methods</h3> Data on patient characteristics, diagnosis, previous treatment and outcomes have been collected since 2011 in Turkish Biologic (TURKBIO) Registry. By the end of December 2017, 338 RA patients, received abatacept from the TURKBIO registry, were included in the analysis. Patients were divided into groups according to the use of glucocorticoid when abatacept therapy was started. Demographic and clinical data including age, sex, disease type, disease duration, and previous or current treatment with DMARDs and biological drug durations are recorded in the database. Kaplan-Meier survival analysis was performed to estimate the drug survival. Subgroups were compared by log-rank. <h3>Results</h3> There were no significant differences in age, gender, seropositivity, tender and swollen joint counts at baseline in the study groups. The disease duration was higher in the glucocorticoid users (p=0.001). Abatacept was the first choice bDMARDs in the 44.5% of glucocorticoid users while it was 68.6% in the glucocorticoid non-users (p&lt;0.001). In addition to abatacept, use of sDMARDs were 96.7% and 53.8% in the glucocorticoid users and non-users, respectively. Baseline VAS-pain and ESR were higher in the glucocorticoid non-users (p=0.047, p=0.009, respectively), but other baseline parameters were similar in glucocorticoid users and non-users. There was no difference between groups in terms of drug survival rates for abatacept (figure 1). <h3>Conclusions</h3> When abatacept treatment started, concomitant use of glucocorticoid at the baseline could not significantly alter drug survival for abatacept in the RA. <h3>Disclosure of Interest</h3> None declared
Report of simultaneous measles outbreaks in two different health regions in Portugal, February to May 2017: lessons learnt and upcoming challenges
Authors: Gonçalo Figueiredo Augusto, Andreia Silva, Natália Pereira, Teresa Fernandes, Ana Leça, Paula Valente, Etelvina Calé, Bárbara Andreia Aguiar, António Martins, Paula Palminha, Elsa Vinagre, Rita Cordeiro, Sílvia Lopo, Paulo Jorge Nogueira
Journal: Eurosurveillance (2019)

In Portugal, measles vaccination coverage and population immunity are high, and no endemic measles cases had been reported since 2004. The World Health Organization classified measles as eliminated in the country in 2015 and 2016, based on data from the previous 3 years. However, in a context of increasing incidence in several European countries in 2016 and 2017, Portugal experienced two simultaneous measles outbreaks with a total of 27 laboratory-confirmed cases (0.3 cases/100,000 population) in two health regions between February and May 2017. Nineteen cases (70.1%) were adults, of whom 12 were healthcare workers. Overall, 17 cases (63.0%) were not vaccinated, of whom five were infants younger than 12 months of age. One unvaccinated teenager died. Genotype B3 was identified in 14 cases from both regions. Measles virus sequencing identified different possible origins of the virus in each region affected. Although measles transmission was stopped in less than 2 months from the first case being notified, these outbreaks represent an opportunity to reinforce awareness of measles diagnosis. We highlight the intensity of the control measures taken and their impact on the rapid control of the outbreaks and also the fact that high vaccination coverage was crucial to stop transmission.
Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer
Authors: Gillian Vandekerkhove, Werner J. Struss, Matti Annala, Heini M.L. Kallio, Daniel Khalaf, Evan W. Warner, Cameron Herberts, Elie Ritch, Kevin Beja, Yulia Loktionova, Antonio Hurtado-Coll, Ladan Fazli, Alan So, Peter C. Black, Matti Nykter, Teuvo Tammela, Kim N. Chi, Martin E. Gleave, Alexander W. Wyatt
Journal: European Urology (2019)
THU0180 Should we include ultrasound in the 1987 acr and 2010 acr/eular classification criteria for rheumatoid arthritis?
Authors: W. Hamdi, M. Sellami, H. Riahi, K. Maatallah, D. Kaffel, M. Chelli-Bouaziz, M.F. Ladeb, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ultrasound imaging (US) is actually considered as a crucial element of the diagnostic process in rheumatic diseases and could be the method of choice in imaging peripheral synovitis, typical feature during rheumatoid arthritis (RA). The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria focused on early-stage RA, and were designed to remedy the deficiencies in the 1987 ACR criteria, but still lacking sensitivity. <h3>Objectives</h3> We undertook this study to investigate whether including the ultra-sonographic data in calculating the 1987 ACR and 2010 ACR/EULAR criteria is useful in diagnosing RA. <h3>Methods</h3> We performed a cross-sectional study of one hundred patients with inflammatory joint pain or synovitis for more than 6 weeks and less than 2 years. An experienced radiologist performed the MSUS scan of 22 joints (2 wrists, 10 metacarpophalangeal joints MCP and 10 proximal interphalangeal joints PIP) unaware of clinical and biological findings. After US assessment, patients were classified as having RA according to ACR/ EULAR 2010 criteria using clinical, biologic and radiographic data (clinical ACR87 or clinical ACR/EULAR2010). Then we calculate those criteria using US data: US-ACR87 including erosion detected in US as a criterion and US-ACR/EULAR2010 including the number of synovitis detected in US as a criterion. <h3>Results</h3> One hundred RA patients were included (77 women and 23 men) with a mean age of 51.8 years.<sup>16–77</sup> The mean disease duration was 10.96.<sup>2 24</sup> Rheumatoid factor and antibodies against cyclic citrullinated peptides were positive in 53% and 25% cases respectively. Sixty-five patients (65%) accomplished the clinical ACR87 criteria and 55 patients (55%) fulfilled the clinical ACR/EULAR2010 criteria for the diagnosis of RA. Using US data eighty patients (80%) accomplished the US-ACR87 criteria and 68 patients (68%) fulfilled the US-ACR/EULAR2010 criteria for the diagnosis of RA. A good correlation was found between clinical and US ACR/EULAR criteria (k=0,684, p=0,000). US score showed a very good sensitivity of 100%, specificity of 67,5%, positive predictive value of 76,9% and negative predictive value of 100% compared to clinical score. In table 1 we summarise correlation between clinical and US ACR/EULAR criteria. <h3>Conclusions</h3> Our study showed that including US data in the classification criteria of RA, will improve diagnostic impact of those criteria during RA management. <h3>Disclosure of Interest</h3> None declared
4D Printing: 3D‐Printed Hydrogel Composites for Predictive Temporal (4D) Cellular Organizations and Patterned Biogenic Mineralization (Adv. Healthcare Mater. 1/2019)
Authors: Joselle M. McCracken, Brittany M. Rauzan, Jacob C. E. Kjellman, Mikhail E. Kandel, Yu Hao Liu, Adina Badea, Lou Ann Miller, Simon A. Rogers, Gabriel Popescu, Ralph G. Nuzzo
Journal: Advanced Healthcare Materials (2019)

In article number 1800788, Ralph G. Nuzzo and co-workers show micro-scaffold hydrogels that are fabricated using the additive manufacturing technique of direct-ink writing (DIW). The hydrogel compositions are optimized for multilayer printing and are used to tune growth compliance by directing the temporal dynamics and spatial distribution of cell attachment without the use of surface-modifying treatments. Image courtesy of Joselle M. McCracken.
AB1061 Multifocal spondylodiscitis in immunocompetent patients
Authors: W. Hamdi, S. bouden, H. riahi, K. Maatallah, M.D. Kaffel, M. bouaziz, M. ladeb, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The prevalence of Infectious spondylodiscitis (SPD) has decreased recentlywith the development of effective means of prevention. Multifocal forms are more common in immunocompromised persons, but may be seen in immunocompetent ones. They are severe, and fortunately remain rare. <h3>Objectives</h3> The aim of our study was to report the clinical, biological, radiological and therapeutic features of multifocal SPD in immunocompetent patients. <h3>Methods</h3> A retrospective study was performed including patients hospitalised in the department of rheumatology between <sup>January 2007</sup> and December 2017. Clinical data, laboratory findings and radiologic features were evaluated. <h3>Results</h3> Six patients were included. Theirmean age was 53 years.<sup>34–81</sup> No comorbidities were found in all patients. The interval between the beginning of the symptomatology and the diagnosis was 3 to 6 months. Fever was noticed in 4 cases. All the patients had inflammatory spinal pain. Two patients had neurologic deficiency: one spinal compression and one root compression. The localization of the infection was lumbar and thoracic in 3 cases, cervical in 1 case and lumbar in 2 cases. MRI showed epiduritis in 3cases and paravertebral abscess in 1 case. The infectious agent was identified by blood cultures in 1 case (Staphylococcus Aureus), by disco vertebral biopsy in 3 cases (tuberculosis) and by brucella serology in 2 cases. All patients underwent antibiotic therapy and immobilisation with a goodoutcome, only one patient needed surgery aiming to decompress the spinal cord. Investigation for immunodeficiency was negative in all patients. <h3>Conclusions</h3> Multifocal SPD in immunocompetent patients remains rare. Its etiology is dominated by tuberculosis. The most frequent localizations are lumbar and thoracic spine. <h3>Disclosure of Interest</h3> None declared
SAT0427 Predictive value of fetal umbilical artery doppler in adverse pregnancy outcomes in patients with lupus nephritis
Authors: D. Chen, Z. Zhan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Compared with the general population, patients with lupus nephritis (LN) are still at high risk of adverse pregnancy outcomes (APOs), including fetal loss, preterm birth and intrauterine growth retardation (IUGR). Umbilical artery is particularly important for placental perfusion and fetal development. Increased umbilical artery resistance could be traced by Doppler velocimetry, which could be used as a screening tool for placenta-related diseases. However, the predictive value in HDP of lupus pregnancies has not been widely assessed. <h3>Objectives</h3> To examine the predictive value of the fetal umbilical artery Doppler on adverse pregnancy outcomes (APOs) in pregnant women with lupus nephritis (LN). <h3>Methods</h3> The clinical data of 158 LN pregnant patients from the First Affiliated Hospital of Sun Yat-sen University were analysed retrospectively. <h3>Results</h3> Totally, 119 were diagnosed before pregnancy and 39 were newly diagnosed during pregnancy. One or more APOs occurred in 74.7% of patients with LN and 40 (25.3%) were without any APOs. Fifty-four of pregnancies (12.2%) resulted in fetal loss. A total of 55 pregnancies were preterm birth, 24 were IUGR, 14 were fetal distress and 9 were neonatal lupus. Doppler pulsatility index (PI), resistance index (RI) as well as S/D value were significantly higher in the APOs groups than in the patients without APOs (p&lt;0.05). The area below the receiver operating characteristic (ROC) curve for PI, RI and S/D all was 0.7 (95%<i>CI</i> 0.6~0.8). PI with cut-off value of 0.9 indicated the highest risk of APOs, with sensitivity of 28.3% and specificity of 97.2%. Regarding 0.6 as the cut-off value for RI to predict APOs, the sensitivity was 45.7% and the specificity was 80.6%. The optimal cut-off value for S/D was 2.5, at which sensitivity (39.1%) and specificity (90.0%) had the best combination. <h3>Conclusions</h3> Pregnancies in LN were more prone to pregnancy loss and preterm birth. Umbilical artery Doppler was a useful monitoring measure for APOs in pregnancies of LN. <h3>Disclosure of Interest</h3> None declared
FRI0109 Drug immunogenicity and the development of paradoxical adverse events with biologic therapies
Authors: C. Ancuta, C. Pomirleanu, R. Paiu, G. Strugariu, L. Petrariu, E. Ancuta, A. Chiriac, R. Chirieac
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Defined as <i>de novo</i> or exacerbation of pathologies that usually responds to biologic agents, paradoxical reactions encompass for a wide spectrum of manifestations (cutaneous, intestinal, ocular) reported during biological therapy (TNF and non-TNF medications) regardless of the underlying rheumatic or non-rheumatic disorder. <h3>Objectives</h3> To assess drug levels (DL) and anti-drug antibodies (ADA) in patients with paradoxical reactions (<i>de novo</i> or exacerbation of psoriasis, uveitis, Crohn's disease) induced by biological drugs (bDMARS) in Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). <h3>Methods</h3> We performed a retrospective observational study in cohorts of consecutive RA (267), PSA (65) and AS (145) undergoing TNF (i-TNF) or non-TNF biologics according to the local recommendations for initiation and monitoring, attending a single academic rheumatology department. All patients were assessed at every 24 weeks months for disease activity and outcomes; supplementary, drug immunogenicity (ADA and DL) was systematically evaluated in patients developing paradoxical adverse events. DL and ADA were measured with an ELISA assay and antibody binding test, respectively. Serum drug levels were considered positive for infliximab if &gt;0.035 µg/mL, for adalimumab &gt;0.024 µg/mL, for etanercept &gt;0.035 µg/mL, rituximab &gt;0.75 µg/mL, while the cut-offs for ADA positivity to infliximab was established at 5AU/ml, for adalimumab at 10AU/mL, etanercept at 142 AU/mL, rituximab 140 AU/mL (ELISA, Progenika) <h3>Results</h3> 42 patients with paradoxical psoriasis (30 with <i>de novo</i> lesions, 18 with palmo-plantar pustulosis, 12 with exacerbation of pre-existent lesions), 12 with paradoxical uveitis (5 with a new onset uveitis) and 3 with paradoxical Crohn's were included in the final analysis. Paradoxical events related to abatacept, certolizumab (one <i>de novo</i> psoriasis per agent) or golimumab (2 new onset uveitis, one flare of Chron's disease) were excluded from the final analysis as no immunogenicity lab tests were provided. Drug induced paradoxical events were described not only with all TNF inhibitors but also with rituximab. DL was in normal range in all these patients; in addition, ADA were either negative, or, if present, had no impact on drug concentration. Furthermore, we found no significant differences in drug levels of TNF inhibitors for RA, PsA and AS. Moreover, no statistical significant differences were observed in the detection of ADA between the three groups. <h3>Conclusions</h3> Patients who develop either true or borderline paradoxical AE have adequate drug levels, with normal ADA concentrations. <h3>Disclosure of Interest</h3> None declared
AB1363 Are you able to cut your meat? – exploring the challenges during the cultural adaptation of the health assessment questionnaire disability index (HAQ-DI) into 130 languages
Authors: C. Acquadro, C. Anfray, P. Bindi, V. Uzun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The disability assessment component of the Health Assessment Questionnaire, the HAQ-DI,<sup>1</sup> developed in US English, assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities – dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asks over the past week "Are you able to …" perform a particular task. The patient's responses are made on a scale from zero (no disability) to three (completely disabled). <h3>Objectives</h3> To explore the challenges faced during the cultural adaptation of the HAQ-DI, focusing on one simple task, i.e., "Are you able to cut your meat?" in the eating category. <h3>Methods</h3> The archives of Mapi Language Services were searched and 130 translations were retrieved, representing 13 language families. The translation methods followed either the standard linguistic validation process [i.e., conceptual analysis, dual translation process (forward, backward translation into English), test with patients and clinician review] or the adjusted process in case of countries using national variants of the same language (i.e., Australian English or English used in India).<sup>2</sup> <h3>Results</h3> In most of the target languages, cutting a whole piece of meat presented in one plate was not a cultural issue. However, in vegetarian-driven cultures or countries where cutting meat was performed while cooking, the item had to be adapted and changed to comply both with the local culture and the concept explored by the item (i.e., fine movement of the upper extremity). For instance, an equivalent of "to cut meat while cooking" was chosen in Korean; "to cut meat (when eating or preparing food)," in Bahasa (Indonesia); "to cut raw vegetables," in Gujarati (India); or "make bite size pieces of your food (e.g., chapatis)" in English for India. <h3>Conclusions</h3> The close collaboration between the developer and the translation teams was essential in finding appropriate conceptual equivalents of the simple task of cutting meat in 13 different language families. <h3>References</h3> [1] Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003Jun 9;1:20. [2] Mear I, Giroudet C. Chapter 1: Linguistic Validation Procedures. In: Acquadro C, Conway K, Giroudet C, Mear I, editors. Linguistic Validation Manual for Health Outcome Assessments. Lyon, France: Mapi Institute; 2012. p. 15–117. <h3>Disclosure of Interest</h3> None declared
Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders
Authors: Bernadette Biondi, George J Kahaly, R Paul Robertson
Journal: Endocrine Reviews (2019)

Thyroid dysfunction and diabetes mellitus are closely linked. Several studies have documented the increased prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. This review critically discusses the different underlying mechanisms linking type 1 and 2 diabetes and thyroid dysfunction to demonstrate that the association of these two common disorders is unlikely a simple coincidence. We assess the current state of knowledge on the central and peripheral control of thyroid hormone on food intake and glucose and lipid metabolism in target tissues (such as liver, white and brown adipose tissue, pancreatic β cells, and skeletal muscle) to explain the mechanism linking overt and subclinical hypothyroidism to type 2 diabetes and metabolic syndrome. We also elucidate the common susceptibility genes and the pathogenetic mechanisms contributing to the autoimmune mechanism involved in the onset of type 1 diabetes mellitus and autoimmune thyroid disorders. An untreated thyroid dysfunction can impair the metabolic control of diabetic patients, and this association can have important repercussions on the outcome of both of these disorders. Therefore, we offer recommendations for the diagnosis, management, and screening of thyroid disorders in patients with diabetes mellitus, including the treatment of diabetic patients planning a pregnancy. We also discuss the major causes of failure to achieve an optimal management of thyroid dysfunction in diabetic patients and provide recommendations for assessing and treating these disorders during therapy with antidiabetic drugs. An algorithm for a correct approach of these disorders when linked is also provided.
Abstract 19842: The Association Between ST-Deviation in aVR in Anterior STEMI Patients Undergoing Primary PCI and Mortality
Authors: Samrudha Jadhav, Anand Joshi, Diane Galbraith, Danielle A Southern, Merril L Knudtson, Bryan J Har
Journal: Circulation (2017)

Introduction: In patients presenting with STEMI treated with fibrinolysis, the presence of ST-segment deviation in ECG lead aVR has been associated with increased short-term mortality. ECG lead aVR has been considered a marker for global myocardial ischemia. Primary PCI results in greater culprit vessel patency rate and is favored in high risk patients. Hypothesis: In patients with Anterior STEMI treated with primary PCI, after adjustment for other ECG and clinical features, the presence of ST-segment deviation in aVR will be associated with increased long-term mortality. Methods: From 2002-2012, we identified 1358 primary PCI cases were of Anterior STEMI without RBBB or LBBB. Of these, 1282 had ECG ST-deviation could be measured in all 12-leads. Patients were followed for up to 3 years. We used Cox proportional hazard models to assess relationship between the presence of ST-deviation in lead aVR to death. We adjusted for sum absolute ST-deviation in all other ECG leads, age, diabetes, and heart failure. ...