tbuckley/cabot-search huggingface dataset:
A7.16 Characterisation of changes in lymphocyte subsets in baricitinib-treated patients with rheumatoid arthritis in two phase 3 studies
Authors: P Emery, I McInnes, MC Genovese, JS Smolen, J Kremer, M Dougados, DE Schlichting, T Rooney, M Issa, S de Bono, WL Macias, V Rogai, SH Zuckerman, PC Taylor
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Baricitinib is an oral, reversible inhibitor of Janus kinase (JAK)1/JAK2 being developed as treatment for patients with RA. Previous studies have shown transient increases in total lymphocyte count within hours of dosing and return to baseline prior to the next dose. We examined changes over time in lymphocyte subsets in RA patients treated with baricitinib or placebo in the phase 3 RA-BUILD and RA-BEACON studies. <h3>Materials and methods</h3> Patients had active RA with insufficient response (IR) to conventional synthetic DMARDs (csDMARDs) (RA-BUILD; N=684) or TNF inhibitors (TNFi) (RA-BEACON; N=527). Patients were randomised 1:1:1 to placebo or 2 or 4mg baricitinib QD for 24 weeks. Lymphocyte subsets and natural killer (NK) cells were quantified by flow cytometry at baseline and Week (wk) 4, wk12, and wk24. Total lymphocyte count was measured at each visit. <h3>Results</h3> Significant improvements in disease activity were seen for baricitinib versus placebo in both studies. Total lymphocyte increases at wk4 for baricitinib were generally within normal ranges. Change in total lymphocyte count was similar at wk12 and wk24 for baricitinib versus placebo. In RA-BUILD/RA-BEACON, increased T-cells/µL (158.3/22.6 and 124.1/170.7 for 2mg and 4mg,p ≤ 0.05), B-cells/µL (66.7/36.8 and 82.9/74.3 for 2mg and 4mg,p ≤ 0.001), and NK-cells/µL (59.5/36.8 and 46.2/77.0 for 2mg and 4mg,p ≤ 0.01) versus placebo were seen at wk4. Decreased T-cells/µL (wk12= -20.9/0.7 and -87.6/-33.1 for 2mg and 4mg; wk24&nbsp;= -117.2/-128.1 and -83.4/-53.8 for 2mg and 4mg,p ≤ 0.05) and NK-cells/µL (wk12&nbsp;= -36.7/-22.0 and -57.0/-22.7 for 2mg and 4mg,p ≤ 0.001 in RA-BEACON; wk24&nbsp;= -41.2/-45.0 and -53.4/-40.9 for 2mg and 4mg, p ≤ 0.05 in RA-BEACON) and increased B-cells/µL (wk12&nbsp;= 65.0/49.3 and 75.1/70.2 for 2mg and 4mg, p ≤ 0.001; wk24= 24.3/22.6 and 55.2/65.0 for 2mg and 4mg,p ≤ 0.001 for 4mg) were seen later for baricitinib groups. Changes in other T- and B-cell populations were variable, but generally reflected these patterns. Decreased NK-cell count did not appear to be associated with an increased incidence of infection. <h3>Conclusions</h3> Baricitinib produced significant clinical improvements in disease activity in csDMARD-IR and TNFi-IR RA patients. Improvements were accompanied by a variety of changes in lymphocyte counts, predominantly within normal ranges. Similar lymphocyte subset assessments will be available in a long-term extension study.
Abstract 853: Prognostic significance of VEGF mRNA in pN0 patients with colorectal cancer
Authors: SC Cesar Wong, Money YY Lam, Brigette BY Ma, Thomas CC Au, Charles ML Chan, Edwin P Hui, John KC Chan, Anthony TC Chan
Journal: Cancer Research (2010)

Abstract Objectives: Recently, we discovered isolated cytokeratin 20 (CK20) positive cells in pN0 lymph nodes (LN) from patients with colorectal cancer (CRC) and molecular dissection of this micrometastasis pathway is essential for us to understand which metastasis-related mRNA genes are involved. Using tumor metastasis quantitative polymerase chain reaction (QPCR) arrays, vascular endothelial growth factor (VEGF) mRNA has the highest median fold change in CK20 positive pN0 LN when compared to CK20 negative pN0 LN from patients with CRC (AACR Infection and Cancer abstract number B47). In this study, we validate the QPCR array results by measuring VEGF mRNA concentration in an independent set of pN0 patients with CRC and examine the prognostic significance of VEGF mRNA in the same cohort of patients. Materials and Methods: Twenty-nine paraffin-embedded pN0 LN specimens with CK20 positive cells and the same number of specimens without CK20 positive cells from patients with CRC detected by immunostaining were retrospectively retrieved from the Department of Pathology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region. Total RNA was extracted from each sample for the quantification of VEGF mRNA using primers and a Taqman minor groove binder probe which labeled with a carboxyfluorescein reporter dye at the 5′-end and a nonfluorescent quencher at the 3′-end (Applied Biosystems, Foster City, USA). All 58 pN0 patients with CRC were follow-up for 48 months from their respective diagnosis for recurrent or metastatic CRC and a recurrent/metastatic curve was plotted using the median copy number of VEGF mRNA as the cut-off point. Results: The median concentration of VEGF mRNA in CK20 positive pN0 LN (35710 copy numbers, range: 5189-51240 copy numbers) was significantly higher than those in CK20 negative pN0 LN (1654 copy numbers, range: 210-4450 copy numbers) (p &amp;lt; 0.0001, Mann Whitney test). Using the median VEGF mRNA copy number (35710) of 29 CK20 positive pN0 patients with CRC as the cut-off point to plot the recurrent/metastatic curves, the time to recurrence or metastasis was significantly shorter for 14 patients with VEGF mRNA concentration &amp;gt; 35710 copy numbers (median recurrence/metastasis = 29.5 months) than for 15 patients with VEGF mRNA concentration ≤ 35710 copy numbers (p &amp;lt; 0.05, log-rank test). Conclusions: VEGF mRNA concentration is significantly correlated to the time of recurrence/metastasis and it may be able to predict the risk of recurrence/metastasis in pN0 patients with CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 853.
Abstract 5164: Using metabolomic flux to uncover new targets for the modulation of breast cancer metastasis
Authors: Lauren D. Van Wassenhove, Michelle L. Wynn, Sepideh Ashrafzadeh, Sofia D. Merajver
Journal: Cancer Research (2012)

Abstract Inflammatory breast cancer (IBC) is the most deadly breast cancer because of its ability to rapidly metastasize, often before the primary lesion is detected. To better understand what drives this highly aggressive form of cancer, we studied central carbon metabolism in IBC. The Warburg effect, which is characterized by high rates of glucose uptake and glycolysis even under aerobic conditions, occurs in most cancer cells and plays an important role in the tumorigenic capacity of breast cancer. Specifically, we examined metabolic changes that occur when breast cancer cells switch from a proliferating phenotype to a highly motile phenotype. In primary tumor formation rapid proliferation is crucial, while in metastasis motility to new sites is critical. We hypothesize that alterations in the regulation of metabolic pathways leads to the direction of energy from proliferation to motility, and that this change is important in the progression of breast cancer towards metastases. Understanding if a coincident metabolic shift occurs when malignant cells switch from a proliferative to a more aggressive motile form may help identify new therapeutics for highly aggressive breast cancers. For our studies, we are using “normal-like” MCF-10A breast cells, which proliferate quickly and move slower than cancer cells, and two highly metastatic breast cancer cell lines (MDA-MB-231 and the IBC-derived line SUM 149), which have the ability to move quickly and proliferate relatively slowly. Using these cell lines as a model, we have examined metabolic changes as cancer progresses. We are conducting targeted metabolomic studies to determine relative concentrations of metabolites in the glycolysis, tricarboxylic acid (TCA) cycle, and mevalonate pathway. In addition, we are using 13C-labeled pyruvate and glucose to measure the transient and steady state flux through these metabolic pathways. Our preliminary results indicate interesting and unexpected changes in both the transient and steady state metabolic fluxes across the different cell lines. In addition, the metabolic flux through the TCA cycle is very active in the metastatic cancer cells despite an increase in glycolysis. In agreement with flux studies of other cancer cell lines, our results suggest that the cancer cells are likely using intermediates from the TCA cycle to generate nucleotides and fatty acids needed for replication. The results from this work, once validated, can be used to identify new therapeutic metabolic targets to modulate breast cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5164. doi:1538-7445.AM2012-5164
Perception versus action: The computations may be the same but the direction of fit differs
Authors: Nicholas Shea
Journal: Behavioral and Brain Sciences (2013)

Abstract Although predictive coding may offer a computational principle that unifies perception and action, states with different directions of fit are involved (with indicative and imperative contents, respectively). Predictive states are adjusted to fit the world in the course of perception, but in the case of action, the corresponding states act as a fixed target towards which the agent adjusts the world. This well-recognised distinction helps side-step some problems discussed in the target article.
Epiphora After Radioactive Iodine Therapy in a Low-Risk Patient
Authors: Heesung Song, Jinho Jeong, Myeong Ju Koh
Journal: Clinical Nuclear Medicine (2015)

It has been demonstrated that radioactive iodine therapy (RIT) is very useful for ablating remnant thyroid tissue or metastatic lesions after total thyroidectomy in well-differentiated thyroid cancer. Epiphora as a result of lacrimal drainage system obstruction is a rare complication of RIT. Previous studies have shown that most patients with epiphora after RIT are old ages, females, and with high cumulative radioactive iodine dose. Here, we report on a case of epiphora with low-risk factors including young ages, male, and 5.5-GBq (150-mCi) dose in the first RIT.
SP0010 Igg4-Related Disease: A Clinical and Therapeutic Overview
Authors: J. Zwerina
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Autoimmune pancreatitis was found to be associated with highy elevated serum immunoglubin G4 (IgG4) levels in 2001. Since then, the disease was recognized as a systemic condition with frequent occurrence of extrapancreatic manifestations. In the following years, IgG4 - Related Disease (IgG4-RD), a fibroinflammatory disorder characterized by tumefactive lesions, dense lymphoplasmacytic infiltrates with IgG4-positive plasma cells, storiform fibrosis and elevated IgG4 serum levels, was defined. Manifestations have been described for nearly every organ system now, and diseases, that have been confined to single organs for a long time, have been charactarized as part of IgG4-RD. The pathophysiology and origin of this rare disease is largely unknown. IgG4RD can affect single or multiple organs, resulting in either diffuse or localized lesions. Clinical presentation is usually subacutely and most patients do not have consitutional symptoms or systemic signs of inflammation. However, life- threatening events such as aortic rupture or liver failure do occur and therefore timely diagnosis and therapy is important. Many, but not all, patients present with strongly elevated serum IgG4 levels. In most organs, a typical histological picture as described above can be found. Currently, there is a lack of data from randomized, controlled trials regarding the treatment of IgG4-RD. Watchful waiting might be adequate for asymptomatic organ involvement. The mainstay of therapy is glucocorticoids, but relapses are common upon GC tapering. Azathioprine, methotrexate and other immunosuppressive drugs are currently used for relapsing disease. Refractory disease has been successfully treated with rituximab. Immunosuppression seems to be more effective during inflammatory stages of the disease than in patients with established fibrosis. <h3>Disclosure of Interest</h3> J. Zwerina Grant/Research support from: Roche, Consultant for: Roche, Conflict with: Roche <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6235
Distinct genomic events in the myeloid and lymphoid lineages in simultaneous presentation of chronic myeloid leukemia and B-chronic lymphocytic leukemia
Authors: B Crescenzi, S Sacchi, R Marasca, P Temperani, R La Starza, C Matteucci, G Bonacorsi, S Romoli, MF Martelli, C Mecucci, G Emilia
Journal: Leukemia (2002)
THU0438 Predictive value of ultrasound on the response to steroid infiltrations in the painful shoulder: A prospective controlled single-blind study of 70 patients:
Authors: P. Zufferey, E. Naredo, Y. Henchoz, A. So
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Acute shoulder pain is a common rheumatologic symptom. Although there are multiple causes, it usually responds well to local steroid infiltration. Ultrasound (US), a simple non-invasive and accessible imaging modality is increasingly used to evaluate a wide spectrum of shoulder lesions in painful shoulder and has also been proposed to guide local steroid injection <h3>Objectives</h3> To investigate the relation between pathological finding on ultrasound and the clinical response to steroid injection in terms of pain (i.e. assessed as rest pain and pain during daily activity) in patients with acute shoulder pain. <h3>Methods</h3> 70 consecutive patients with acute shoulder pain were assessed clinically and by US. US findings were categorized, and an individual patient can have pathologies fulfilling &gt;1 category. Patients were randomized to receive either a standard "blind" subacromial injection of 7mg of betamethasone or a US-guided injection directed toward the structure more susceptible to be the cause of pain. Follow-up evaluations were performed by an independent assessor who was not aware of the results of the initial US and clinical assessments. Initial US diagnoses were compared with respect to changes in the VAS pain score at 2, 6 and 12 weeks after the injection. We performed single and multiple regression analysis on each US diagnosis, in order to find one or more predictors of response. <h3>Results</h3> The US findings and changes in night visual analogue scale (VAS) pain scores for each category are summarized in the following table. At 2 and 6 weeks, all US diagnostic categories showed significantly reduced VAS pain scores compared to baseline. There was a clear trend toward reappearance of pain by 12 weeks in most categories. Single and multiple regression analyses showed that the presence of calcification was the only significant predictor of a better response compared to other US diagnoses. This was valid only at 2 weeks post injection, for activity pain (p: 0.003) as well as rest pain (p: 0.05). The method of infiltration did not influence the results. <h3>Conclusions</h3> Steroid injection significantly reduced pain in patients with acute shoulder pain whatever the initial US diagnosis. The presence of periarticular calcification is the only individual predictor of a better response, but only up to 2 weeks. <h3>Disclosure of Interest</h3> None Declared
Radioactive Isotopes in a Community Hospital
Authors: John W. Turner
Journal: New England Journal of Medicine (1955)

THIS year is the twentieth anniversary of the first elaboration of labeled or tagged radioactive isotopes. In May, 1938, Hertz and his associates1 presented a summary of studies in which radioactive iodine was used as an indicator of thyroid function, soon followed by a paper2 on the application of radioactive iodine in the therapy of Graves's disease. Thirteen years ago Dr. John Lawrence3 gave the Caldwell Lecture of the American Roentgen Ray Society, in which he recited numerous biologic and medical applications of various radioactive isotopes already accomplished. Many other physicians and medical nuclear physicists were exploring new possibilities of . . .
FRI0142 Patient-Reported Disease Activity and Outcome in Male versus Female Patients of the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) Cohort: Table 1.
Authors: S. Arends, F. Maas, E. van der Veer, R. Bos, M. Efde, M.K. Leijsma, H. Bootsma, E. Brouwer, A. Spoorenberg
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> There are differences in clinical presentation of ankylosing spondylitis (AS). Women tend to have milder disease and may therefore be underdiagnosed. Male AS patients are more likely to develop spinal radiographic damage. <h3>Objectives</h3> The aim of the present study was to investigate whether there are differences in patient-reported assessments of disease activity, physical function, and quality of life between male and female patients with axial spondyloarthritis (SpA). <h3>Methods</h3> All consecutive patients from the Groningen Leeuwarden Axial SpA (GLAS) cohort who visited the outpatient clinic between January 2011 and December 2012 were included in this cross-sectional analysis. All patients fulfilled the modified New York criteria for AS (&gt;90%) or the ASAS criteria for axial SpA. Disease activity was assessed using Bath AS disease activity index (BASDAI), AS disease activity score (ASDAS; calculated from BASDAI questions 2, 3 and 6, patient global assessment of disease activity (GDA), and C-reactive protein (CRP)), swollen joint index (range 0-44), and tender joint index (range 0-46). Physical function was assessed using Bath AS functional index (BASFI) and quality of life using AS quality of life (ASQoL) questionnaire. <h3>Results</h3> Of the 469 included patients, mean age was 45 years (SD ±13), mean duration of symptoms was 17 years (range 0-61), 66% were male, and 80% were HLA-B27+. Males were significantly older, had longer disease duration, and were more frequently HLA-B27+ compared to females. Extra-articular manifestations, comorbidity, and current use of NSAID, DMARD, and anti-TNF were comparable between both groups. Patient-reported measures of disease activity (BASDAI, patient GDA, and tender joints) and outcome (BASFI and ASQoL) were significantly higher in female compared to male patients. ASDAS, capturing both subjective and objective aspects of disease activity, was also significantly higher in females. This difference can be explained by patient-reported aspects of the ASDAS, since CRP levels were comparable between male and female patients (Table 1). Differences remained statistically significant after correcting for age, disease duration, and HLA-B27 status. <h3>Conclusions</h3> This cross-sectional study shows that patient-reported measures of disease activity and outcome as well as ASDAS were significantly worse in female axial SpA patients. We recommend to be aware of these differences when interpreting patient-reported measures in research and clinical practice. <h3>Acknowledgements</h3> The GLAS cohort was supported by an unrestricted grant from Pfizer. Pfizer had no role in the design, conduct, interpretation, or publication of this study. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4330
Auricular Fibrillation in Normal Hearts
Authors: Hugh H. Hanson, David I. Rutledge
Journal: New England Journal of Medicine (1949)

AURICULAR fibrillation is not always associated with organic heart disease, and its presence may be the only sign attracting the examiner's attention to the heart. All cases of auricular fibrillation are fairly readily separated into two significant clinical groups — a minor group occurring in anatomically normal hearts and a major group occurring in damaged and diseased hearts. Emphasis should be placed on auricular fibrillation occurring in normal hearts because of its excellent prognosis, since this arrhythmia is most frequently observed in gravely damaged and decompensated hearts in which the prognosis is rather ominous.Auricular fibrillation occurring in normal hearts . . .
Serum Antibodies to L-Type Calcium Channels in Patients with Amyotrophic Lateral Sclerosis
Authors: R. Glenn Smith, Susan Hamilton, Franz Hofmann, Toni Schneider, Wolfgang Nastainczyk, Lutz Birnbaumer, Enrico Stefani, Stanley H. Appel
Journal: New England Journal of Medicine (1992)

Sporadic amyotrophic lateral sclerosis is a chronic, progressive degenerative disease of the motor neurons of the spinal cord and motor cortex. The cause is unknown. Recent electrophysiologic studies in animals indicate that immunoglobulins from patients with this disease alter presynaptic voltage-dependent calcium currents and calcium-dependent release of neurotransmitters. To determine whether similar interactions might be identified biochemically, we used an enzyme-linked immunosorbent assay (ELISA) to detect the reaction of serum IgG with purified complexes of L-type voltage-gated calcium channels from rabbit skeletal muscle. The results from patients with amyotrophic lateral sclerosis were compared with those obtained from patients with other types of motor neuron disease, patients with autoimmune and non-autoimmune neurologic diseases, and normal subjects.Serum samples from 36 of 48 patients with sporadic amyotrophic lateral sclerosis (75 percent) contained IgG that reacted with L-type calcium-channel protein, and serum reactivity on ELISA correlated with the rate of disease progression (Spearman rank-correlation coefficient, 0.62). Reactive serum was present in only 1 of 25 normal subjects and 1 of 35 control patients with no motor neuron disease. Antibodies to L-type voltage-gated calcium channels were identified in 6 of 9 patients with Lambert-Eaton syndrome, and in 3 of 15 patients with Guillain-Barré syndrome.Antibodies to L-type voltage-gated calcium channels are present in the serum of patients with amyotrophic lateral sclerosis, and antibody titers correlate with the rate of disease progression. Together with previous data, these results suggest a role for autoimmune mechanisms in the pathogenesis of sporadic amyotrophic lateral sclerosis.