tbuckley/cabot-search huggingface dataset:
THU0059 Reduction of inflammation with abatacept and tocilizumab results in lower N-terminal pro brain natriuretic peptide levels in patients with rheumatoid arthritis: Results from two prospective cohort studies:
Authors: I.V.D. Oever, M.T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) patients are at increased risk of heart failure (HF). The chronic inflammatory state in RA is associated with increased levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker for HF. Recently, a study demonstrated that NT-proBNP levels in RA patients decreased under TNF-blocking therapy. It is unknown whether this is also observed in biologics with another mode of action. <h3>Objectives</h3> To evaluate the effects of abatacept and tocilizumab therapy on NT-proBNP levels. <h3>Methods</h3> In 34 RA consecutive patients starting with abatacept (10 mg/kg every 4 weeks) and 14 consecutive RA patients starting with tocilizumab (8 mg/kg every 4 weeks), disease activity parameters and serum samples were collected at baseline and after 12 weeks of therapy. Clinical response was assessed using EULAR response criteria. Responding patients comprised both good and moderate EULAR responders. NT-proBNP levels were measured by the Elecsys 2010 electrochemiluminescence method (Roche diagnostics). For statistical analyses t-tests and linear regression were used. <h3>Results</h3> NT-proBNP levels did not change significantly after 12 weeks (p=0.6) and there were no significant differences in NT-proBNP levels at baseline or after 12 weeks of treatment between the tocilizumab and abatacept group (p=0.16 and p=0.3 resp.). 34 patients (71%) were EULAR responders, (6=12% good, 28=88% moderate) and 14 patients (29%) were non-responders. Baseline DAS28, CRP and BSE were higher, though not significantly, in responders compared to non-responders (table). Baseline NT-proBNP levels were higher in responders versus non-responders (p=0.044). Change in NT-proBNP levels after 12 weeks of treatment was significantly different between responders and non-responders (p=0.002), with decreasing NT-proBNP levels in responders and increasing levels in non-responders. <h3>Conclusions</h3> There was a remarkable difference in the course of NT-proBNP levels between EULAR responders and non-responders, as responders started with higher baseline levels which decreased significantly under both abatacept and tocilizumab treatment, while in contrast the NT-proBNP levels of non-responding patients increased. These findings indicate favourable effects of abatacept and tocilizumab on cardiac function in RA patients responding to treatment and underscore the importance of tight control of systemic inflammation in order to decrease CV risk. <h3>Disclosure of Interest</h3> None Declared
A comparison of outcome in adolescent- and later-onset bipolar manic- depressive illness
Authors: G A Carlson, Y B Davenport, K Jamison
Journal: American Journal of Psychiatry (1977)

The authors hypothesized that childhood-and adolescent-onset bipolar manic-depressive patients might have a more severe or a different type of affective disorder; early-onset patients were therefore compared with patients whose illness onset was after the age of 45. The results indicate that early age of onset is not a factor in the variable course and prognosis of manic-depressive illness.
Dosimetric Analyses of Kidneys, Liver, Spleen, Pituitary Gland, and Neuroendocrine Tumors of Patients Treated With 177Lu-DOTATATE
Authors: Santosh Kumar Gupta, Suhas Singla, Parul Thakral, Chandrasekhar Bal
Journal: Clinical Nuclear Medicine (2013)

Objectives The aim of this work was to calculate the radiation absorbed dose to kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors (NETs) of patients treated with 177Lu-DOTATATE. Methods We enrolled 61 patients (male/female patients, 40/21) with mean age of 48.1 ± 15.3 years affected by different types of NETs diagnosed with 68Ga-DOTANOC PET-CT and biochemical markers. For radiation protection of kidneys, amino acid mixture (lysine and arginine) was coinfused; 3.7 to 7.4 GBq (100–200 mCi) of 177Lu-DOTATATE was infused to each patient over 30 minutes. Each patient underwent a series of 9 whole-body scans at 30 minutes (prevoid) and 4, 8, 12, 24, 48, 96, 144, and 168 h. The organs included in dosimetric calculation were kidney, liver, spleen, pituitary gland, and NETs. All dosimetric calculations were done using the OLINDA/EXM 1.0 software. Results Physiological uptake of 177Lu-DOTATATE was seen in all patients in kidneys, liver, spleen, and pituitary gland. Radiation absorbed doses were calculated: 0.57 ± 0.09 mGy/MBq for kidneys, 0.27 ± 0.05 mGy/MBq for liver, 1.17 ± 0.14 mGy/MBq for spleen, 0.058 ± 0.011 mGy/MBq for pituitary gland, and 3.41 ± 0.68 mGy/MBq for NETs. Conclusions The maximum cumulative activity of 177Lu-DOTATATE that can be safely administered to a patient within permissible renal threshold in our study was found to be 40 GBq (1100 mCi). However, there are considerable interpatient differences in absorbed doses of all organs requiring individualized dosimetry for optimizing tumor dose.
FRI0112 Ethnic minority rheumatoid arthritis consortium (EMRAC): A prospective clinical database:
Authors: G. Kerr, Y. Yazici, Y. Sherrer, R. Nair, E. Treadwell, A. Mosley-Williams, L. Espinoza, I. Garcia-Valladares, A. Ince, J. Huang, C. Nunziato, W.A. McCracken, C. Swearingen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sparse data exist regarding minority ethnic groups with RA. EMRAC was developed to accrue prospective RA related clinical data in "real-world" settings serving ethnic minority patients in the United States. <h3>Methods</h3> RA of self-reported ethnicity, and seen at 9 US sites are enrolled. Patient demographics, comorbidities, disease-related characteristics are collected. Analyses of overall differences in clinical variables between racial groups was performed using Kruskal-Wallis for continuous variables and exact tests for qualitative variables; post-hoc pairwise comparisons between racial groups were made with the Wilcoxon rank sum test and were adjusted using the Bonferonni correction (p&lt;0.008 for significance). <h3>Results</h3> To date, 502 RA patients have been enrolled (Table 1). Significant differences amongst ethnic groups were observed in age, education, RAPID3, DMARD use, biologics use, and the comorbidities of hypertension, diabetes, and cigarette use ever. African Americans were on the least amount of biologics, whereas Caucasians had least amount of disease activity compared to African Americans and Hispanics. All comorbid conditions were more common among minorities compared to Caucasians. <h3>Conclusions</h3> EMRAC provides important clinical data in an underrepresented population, the results of which may help address differences in medication use and potential challenges in access and guide interventions that improve outcomes. <h3>Disclosure of Interest</h3> G. Kerr Grant/Research support from: Genentech and Biogen IDEC, Inc, Y. Yazici Grant/Research support from: Abbott, BMS, Centocor, Genentech, Consultant for: Abbott, BMS, Genentech, Celgene, UCB, Y. Sherrer Grant/Research support from: AstraZeneca, Mercke, UCB, Sanofi Adventis, Celgene, Lily, Roche, Amgen, Wyeth, Pfizer, Novartis, Speakers Bureau: AstraZeneca, Human Genome Science, Amgen, Pfizer, Wyeth, R. Nair: None Declared, E. Treadwell: None Declared, A. Mosley-Williams: None Declared, L. Espinoza: None Declared, I. Garcia-Valladares: None Declared, A. Ince: None Declared, J. Huang: None Declared, C. Nunziato: None Declared, W. McCracken: None Declared, C. Swearingen: None Declared
AB1316 Higher functional disability was the key element leading to substantial difference between the EQ-5D and the SF-6D utility measures in early arthritis: Results from the ESPOIR cohort:
Authors: C. Gaujoux-Viala, B. Fautrel, K. Hosseini, R.-M. Flipo, F. Guillemin, A.-C. Rat
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The EQ-5D, a 5-dimensional multi-attribute questionnaire, and the SF-6D, derived from the SF36, are 2 indirect utility measures widely used to calculate Quality-adjusted life-years (QALYs) in order to assess health benefits. <h3>Objectives</h3> 1) To assess which variables at baseline are associated with EQ-5D and SF-6D in early arthritis 2) To assess which variables at baseline are associated with substantial utility difference between EQ-5D and SF-6D <h3>Methods</h3> - <i>Patients:</i> included in the French nationwide cohort of early arthritis ESPOIR (at least 2 swollen joints for less than 6 months and suspicion of RA). - <i>Data available:</i> EQ-5D and SF-6D utility measures were assessed in 813 patients with EA. Bio-clinical variables and X-rays were also recorded. - <i>Analysis:</i> The determinants of EQ-5D and SF-6D at baseline were assessed by multivariate linear regression. Multivariate linear and logistic regressions were used to determine which specific aspects of early arthritis were independently associated with the difference between the 2 utility measures (continuous and dichotomous: |SF-6D – EQ5D|&gt;0.03, minimal important difference, MID) [ref]. <h3>Results</h3> At baseline, mean values were 0.50±0.32 (range -0.53 to 1) for EQ-5D and 0.58±0.11 (range 0.30 to 0.92) for SF-6D. In the multivariate linear regression model, higher HAQ, lower mental component of the SF-36 (MCS), higher CRP, higher patient global assessment and be employed were significant determinants of a lower EQ-5D. HAQ and MCS scores explained 56 and 4% of the variance respectively. In the multivariate linear regression model, higher HAQ, lower MCS, higher DAS28, higher pain at rest, higher patient global evaluation, and be employed were significantly associated with lower SF-6D. HAQ and MCS scores explained 49 and 22% of the variance respectively. Higher difference between the 2 utility values (mean 0.083 [range -0.469 to 0.891]) was explained by higher HAQ, lower number of swollen joint count, and higher CRP. The majority of patients presented a difference between the 2 utility values&gt;0.03=MID (88%). In the logistic regression model, only higher disability was associated with |SF-6D –EQ5D|&gt;0.03: OR=1.68 [1.13;2.50]. <h3>Conclusions</h3> there is systematic disagreement between EQ-5D and SF-6D in EA, especially in patients with worse clinical outcomes. Higher functional disability was the key element leading to substantial difference between the 2 utility measures in EA patients. <h3>References</h3> Marra CA, et al. Soc.Sci.Med. 2005;60:1571-1582 <h3>Disclosure of Interest</h3> None Declared
Kentucky Scientists Combine Reading and Cancer Prevention For Low-Literate Women
Authors: J. Siegfried
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Kentucky Scientists Combine Reading and Cancer Prevention For Low-Literate Women Get access Juliette Siegfried Juliette Siegfried Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 19, 2 October 1991, Pages 1374–1375, https://doi.org/10.1093/jnci/83.19.1374 Published: 02 October 1991
Stimulated Salivary Pertechnetate Clearance Revisited
Authors: ROMAIN DEMANGEAT, D. D. S, ANNE DIDON-PONCELET, JEAN CHERFAN, JEAN-LOUIS DEMANGEAT
Journal: Clinical Nuclear Medicine (2000)

The stimulated salivary clearance of Tc-99m pertechnetate (SSCP) introduced in 1985 by Blue and Jackson is revisited here in patients with known or possible salivary disorders and correlated with most commonly cited and up-to-date quantitative indices obtained from standard dynamic salivary scintigraphy.An SSCP test was performed after dynamic salivary scintigraphy in 19 patients with oral or ocular dryness, among whom 7 had Sjögren's syndrome. Many scintigraphic indices were calculated: salivary to background ratio (S/B[t]), background-corrected uptake U[t]), maximal uptake (Umax), cumulative gland uptake (CGU), initial slope of the uptake curve (IS), stimulated excretion velocity (SEV), stimulated excretion fraction (SEF), and excreted activity (EA).The SSCP test was well tolerated, except in two patients in whom it had to be interrupted. Clearance values ranged from 5 to 40 ml/minute, with a clear-cut bimodal distribution centered around 15 to 20 ml/ minute. Six of the seven patients with Sjögren's syndrome had values less than 15 ml/minute. SSCP was closely correlated with all uptake indices (S/B, U, Umax, CGU, and IS) and uptake-related indices (EA, ISxSEF) (P < 0.01). A poor correlation was found with the excretion index SEV (P = 0.06) and none with SEF.SSCP is a quick and objective means to investigate the sicca syndrome that may be useful in most clinical situations. It reflects the parenchymatous salivary gland function and will provide a means to assess and predict salivary gland involvement. Dynamic salivary scintigraphy remains necessary in very early stages because of its high sensitivity rate and ability to locate the impaired gland, or in severe stages in which lemon juice could be deleterious.
Putting humanity back into medicine.
Journal: Canadian Medical Association journal (1972)

I read with interest the article by the HRH, The Prince of Wales1 and find his concept of healthcare refreshingly warm. What he calls as ‘an integrated approach to medicine and health’ is nothing more than the real essence of medicine: caring. The principles he outlines are broad and will be useful for not only UK but the entire international medical community. What he advocates is essentially nothing more than putting up a humane side to medicine and healthcare. When medical students enter the profession everyone has just one aspiration – to treat patients, take care of the sick, relieve humanity of pain and suffering. However, in the course of their profession which currently relies on ‘mechanistic and technological aspects’ they do start having the ‘notion of the body as a machine’. We need doctors to feel like the way they felt the first day in medical college, restoring in them the reason they joined medicine for.

Medicine's glory does not lie in making diseases go kaput but in alleviating the pain and suffering of the sick and the afflicted.
Presentation with gastrointestinal symptoms and high case fatality associated with group W meningococcal disease (MenW) in teenagers, England, July 2015 to January 2016
Authors: Helen Campbell, Sydel R Parikh, Ray Borrow, Ed Kaczmarski, Mary E Ramsay, Shamez N Ladhani
Journal: Eurosurveillance (2016)

Atypical clinical presentations associated with group W meningococcal disease (MenW) are well-described and include pneumonia, septic arthritis, endocarditis and epiglottitis/supraglottitis. Following anecdotal reports of teenagers presenting with predominantly gastrointestinal symptoms, we undertook a case review of MenW cases in 15 to 19 year-olds diagnosed in England between July 2015 and January 2016. Of the 15 cases, seven presented with a short history of nausea, vomiting and diarrhoea; five of these seven cases died within 24 hours of presentation to hospital.
Progression of Diabetic Retinopathy after Pancreas Transplantation for Insulin-Dependent Diabetes Mellitus
Authors: Robert C. Ramsay, Frederick C. Goetz, David E.R. Sutherland, S. Michael Mauer, Leslie L. Robison, Herbert L. Cantrill, William H. Knobloch, John S. Najarian
Journal: New England Journal of Medicine (1988)

We studied the effect of successful pancreas transplantation and consequent normoglycemia (mean total hemoglobin A1, 7.0 percent; range, 5.8 to 8.3) on visual function and diabetic retinopathy in 22 patients with Type I diabetes mellitus (study group). Sixteen similar patients in whom pancreas transplantation had been unsuccessful (mean total hemoglobin A1, 12.0 percent; range, 8.0 to 18.0) served as a control group. The majority of patients in both groups had advanced proliferative retinopathy. At a mean follow-up of 24 months we found no significant difference between the groups in the rate of progression of retinopathy, expressed as a score. Success of the transplantation did not prevent progression of retinopathy across the range of retinopathy studied. Progressive retinopathy was observed more commonly in patients with low retinopathy scores (nonproliferative or mild proliferative retinopathy) at base line in both the study group (13 of 17 eyes, or 76 percent) and the control group (7 of 12 eyes, or 58 percent). Further analysis suggested the possibility that after three years of euglycemia, the study group had less deterioration than the control group, particularly in eyes with advanced retinopathy. We observed no difference in the rate of loss of vision between the two groups. This study provides evidence that pancreas transplantation and subsequent normoglycemia neither reverse nor prevent the progression of diabetic retinopathy. (N Engl J Med 1988; 318:208–14.)
Halothane–Morphine Compared with High-Dose Sufentanil for Anesthesia and Postoperative Analgesia in Neonatal Cardiac Surgery
Authors: K.J.S. Anand, P.R. Hickey
Journal: New England Journal of Medicine (1992)

Extreme hormonal and metabolic responses to stress are associated with increased morbidity and mortality in sick adults. We hypothesized that administering deep opioid anesthesia to critically ill neonates undergoing cardiac surgery would blunt their responses to stress and might improve clinical outcomes.
Abstract 2998: BRG1 (SMARCA4) protein loss has profound effects on the transcriptome of non-small cell lung cancer (NSCLC) cell lines
Authors: Wei Zhang, Yibing Yao, Jingsheng Yan, Yu-An Zhang, Jonathan Rios, Luc Girard, Alexander Pertsemlidis, Ward Wakeland, Yang Xie, Luisa M. Solis, Ignacio I. Wistuba, Samir M. Hanash, John D. Minna, Adi F. Gazdar
Journal: Cancer Research (2012)

Abstract Purpose: To study the gene expression profile of NSCLC cell lines with BRG1 protein loss. Background: BRG1 is the major catalytic subunit of the SWI/SNF chromatin remodeling complex and provides ATPase activity necessary for transcriptional regulation of multiple cellular pathways. BRG1 is frequently inactivated in lung cancers and loss of BRG1 is correlated with poor prognosis. Methods: Sixty eight NSCLC cell lines were analyzed. BRG1 protein was detected by western blotting using nuclear extracts. SMARCA4 deletions or mutations were identified by NextGen sequencing and/or Sanger sequencing using genomic DNA or cDNA. Published reports and SNP analysis were also used to verify our results. Gene expression profiles were determined by Illumina human WG-6 V3 beadchip. Microarray expression data was analyzed by Significance Analysis of Microarray (SAM) and Hierarchical clustering analysis. Results: Twenty five NSCLC cell lines had lost BRG1 protein expression. Sequencing analysis found homozygous mutations (deletions, nonsense, splicing site) in twenty two of the lines. Among forty three NSCLC cell lines with BRG1 protein expression, five had homozygous missense mutations, four had heterozygous mutations. Gene expression profiling demonstrated that nearly 1500 transcripts were differentially up or down regulated (false discovery rate &amp;lt;5%) among the cell lines without BRG1 protein compared to the ones with WT BRG1. These transcripts are involved in many important cellular functions including proliferation, adhesion, epithelial-mesenchymal transition, signaling pathway, steroid receptor and oncogene expression. Hierarchical clustering analysis using these transcripts distinguished NSCLC cell lines without BRG1 protein as a group, different from other NSCLC cells as well as immortalized respiratory epithelial cells, while NSCLC cell lines with BRG1 missense mutations showed heterogeneity of expression patterns. Conclusions: BRG1 protein loss is frequent in lung cancer cells and has a distinct signature and profound effects on the transcriptome of NSCLC cell lines. Our findings support the concept that BRG1 functions as a “master regulator of master regulators.” 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 2998. doi:1538-7445.AM2012-2998
<i>PTEN</i>— Linking Metabolism, Cell Growth, and Cancer
Authors: Ulf Smith
Journal: New England Journal of Medicine (2012)

Both obesity and type 2 diabetes are characterized by a state of insulin resistance, usually defined as a reduction in the ability of insulin to exert its metabolic effects in key target tissues. Insulin resistance is also thought to confer an increased risk of a variety of cancers.1,2 The putative mechanisms by which insulin resistance would increase the risk of oncogenesis involve hyperinsulinemia and elevated levels of insulin-like growth factor I (IGF-I), adipokines, and other growth factors.1,3 Insulin is both a growth factor and a metabolic hormone, and cancer cells often express insulin receptors, IGF-I receptors, and chimeric . . .
AB0272 Rheumatoid factor determines structural progression of rheumatoid arthritis also independently of disease activity:
Authors: D. Aletaha, F. Alasti, J.S. Smolen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The presence of rheumatoid factor (RF) is prototypic for rheumatoid arthritis (RA) and serves diagnostic and prognostic purposes. RF is associated with joint damage, but it is not clear if this is only due to its effects on disease activity or whether there are also independent effects. <h3>Objectives</h3> We investigated whether the higher radiographic progression (change in total Sharp score, ΔTSS) seen in RF positive patients is dependent or independent of higher levels of disease activity, or both. <h3>Methods</h3> We used methotrexate treatment arms from five different RA trials and compared ΔTSS in RF negative and RF high positive patients before and after matching for other prognostically important variables. The high positive positive group was selected to achieve a clear contrast in RF levels despite matching for other variables, and was defined as being above the median of all positives. We used Wilcoxon test for statistical comparison, and a number of sensitivity analyses to see if the results were robust. <h3>Results</h3> Among 687 patients, 124 (18.1%) were RF negative, 562 (81.9%) RF positive, and 343 (50.0%) high positive (RF&gt;160 U/ml). One year ΔTSS was 1.03±5.83, 3.23±8.10 and 3.58±8.18 (p&lt;0.0001), respectively. Aside from RF, progression was associated with duration of RA, baseline damage, CRP and ESR. After matching for these variables, duration of RA, baseline disease activity indices, functional scores, and TSS were essentially identical in the matched 61 RF negative and 61 RF high positive patients. Nevertheless, the ΔTSS was significantly lower in the RF negative compared to their matched RF high positive counterparts (0.52±2.47 vs 3.09±8.28, respectively; p=0.029; table), and was seen particularly for erosions (0.31±1.88 vs. 2.07±5.62; p=0.035), but numerically also for joint space narrowing (0.21±1.26 vs. 1.02±3.31; p=0.162). Sensitivity analyses looking at the area under the curve of risk factors instead of baseline values only, as well as looking at the second year progression, supported the findings in the main analysis; no effect of RF on progression was seen in methotrexate plus TNF-inhibitor treated patients; the level of RF also appeared to be of relevance in an analysis of 29 matched triplets, which also included low positive patients (RF negatives: 0.19±2.47; low positive: 1.15±3.72; and high positive: 3.77±10.8; p=0.19 by Kruskal-Wallis test). <h3>Conclusions</h3> Our data indicate that damage progression in seropositive RA patients is partly related to higher levels of disease activity, but partly also to independent effects of RF, particularly on bone damage. This identifies RF as an important independent risk factor for structural damage, and calls for an even more consequent pursuit of disease activity targets in seropositive RA patients. <h3>Disclosure of Interest</h3> None Declared