tbuckley/cabot-search huggingface dataset:
P203 Addressing low surgical resection rates for Non Small Cell Lung Cancer: local intervention to address high levels of emergency presentations at late stage should be effective.
Authors: EM Hadley
Journal: Thorax (2012)

<h3>Introduction</h3> The National Lung Cancer Audit is a benchmarking tool for cancer networks and individual MDT’s. The national average resection rate for all lung cancer patients is 13.7%. The NLCA recommend that all MDTs with a resection rate for NSCLC below 14%, and for stage 1a–2b below 52% should be reviewed to ensure that patients are being offered appropriate access to thoracic surgical expertise. In the 2011 report our MDT had a resection rate for NSCLC of 7.8%. In light of this a review of all cancer patients was carried out. <h3>Results and discussion</h3> The resection rate for stage 1a-2b NSCLC patients was 48% which is similar to the national average. However the number of patients presenting with operable stage 1a-2b disease was unusually low at 12%. An in depth review of 18 patients with operable NSCLC showed that there were four patients that did not have a curative resection. Two were performance stage 3–4 at presentation, one had a tumour in an inoperable location and the fourth had significant co-morbidities precluding surgery. The opportunity for patients to be offered surgical treatment of stage 1a-2b NSCLC at this MDT is within national targets. However the low figure on the LUCADA data is due to an unusually high proportion of patients (88%) presenting with stage 3–4 disease. This is refected locally where we also have very high rates of lung cancer presenting via emergency admissions, around 70%. The national average is around 30–40%, a figure which is already considered unacceptable. <h3>Conclusion</h3> In order to improve the rate of curative resection and improves survival for our population the key intervention is to diagnose more NSCLC at an early stage. We need to target the local population to present early, and empower primary care to refer early. We will study the impact of the 2012 National Lung Cancer Awareness Programme with interest, although it is likely that a further local campaign targeted at our specific community may be needed if we are to turn around local resection rates.
AB0193 IL-2 therapy in murine lupus nephritis leads to an expansion of intrarenal FOXP3+ regulatory T cells
Authors: A. Rose, J.Y. Humrich, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an acquired IL-2 deficiency, which leads to a homeostatic imbalance between regulatory T cells (Treg) and effector T cells. Recently, we have shown that compensation of the IL-2 deficiency in diseased lupus mice by treatment with recombinant IL-2 (IL-2) ameliorates already established disease by promoting the homeostatic proliferation of regulatory T cell (Treg) in the lymphoid organs (Humrich et al, PNAS 2010). <h3>Objectives</h3> The aim of this study was to investigate the impact of IL-2 therapy on intrarenal Foxp3+ Treg and kidney infiltrating CD4+ T cells in (NZBxNZW) F1 mouse model of lupus nephritis. <h3>Methods</h3> Aged-matched (NZBxNZW) F1 mice were treated with recombinant IL-2 either over period of 24h or over a long-term period of 20 days with PBS treated mice as a control group. Phenotyping of intrarenal T cell were done by flow cytometry analyses. <h3>Results</h3> Our preliminary data of short term IL-2 treated (NZBxNZW) F1 mice showed an increase in numbers and frequency of CD4+Foxp3+ Tregwithin IL-2 treated mice compared to control mice and also increased the proliferation of FoxP3+ regulatory T cells. However, long-term IL-2 treatment mice over a period of 20 days showed a consistent percentage of CD4+FoxP3+ cells. Also the total numbers of kidney infiltrating CD4+ T cells were reduced during long-term experiment with reduced signs of cellular activation. <h3>Conclusions</h3> This preliminary data could show that a supplementary short-term IL-2 treatment expands the number and frequency of the intrarenal Treg pool. On the other hand, long term IL-2 treatment diminishes the numbers of kidney infiltrating CD4+ Tcon and their cellular activity. These results points out the important role of intrarenal Treg for the suppression of kidney disease in lupus mice and may in part explain the delay of disease progression induced by treatment with IL-2 and might give additional rationales for an IL-2 based immunotherapy of human disease. <h3>References</h3> Humrich, JY et al. (2010). Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci USA 107, 204-9 <h3>Disclosure of Interest</h3> None Declared
Abstract 5738: Spectrum of malignancies in patients with end-stage renal disease
Authors: Fatma M. Shebl, Eric A. Engels
Journal: Cancer Research (2010)

Abstract Background: Patients with end-stage renal disease (ESRD) are prone to many complications and high mortality. Overall, ESRD patients are at modestly increased cancer risk. Potential mechanisms by which ESRD might induce cancer include underlying medical conditions, altered immune status due to uremia, and medical treatments. Associations with specific cancers have not been widely studied. Methods: We conducted a population-based case-control study among elderly U.S. adults using Surveillance, Epidemiology, and End Results (SEER) Medicare linked data. After excluding individuals with HIV or history of organ transplant, the study included 1,029,695 cancer cases (identified in SEER) and 99,610 controls, frequency matched by gender, race, age, and calendar year (1992-2007). ESRD was defined by presence of Medicare claims for dialysis in each of the 3 months prior to selection. Logistic regression was used to calculate odds ratios (ORs) adjusted for matching factors. Results: ESRD was present in 0.33% of cancer cases vs. 0.31% of controls (OR 1.13; 95%CI 1.0-1.27, p=0.04). We observed significant excess risk of cancers of the stomach (OR 1.67; 95%CI 1.34-2.08), small intestine (2.02; 1.31-3.12), colon (1.29; 1.11-1.51), liver (1.72; 1.38-2.15), pancreas (1.35; 1.09-1.68), lung (1.30; 1.13-1.49), cervix (1.94; 1.25-3.00), vagina (3.08; 1.43-6.64), penis (4.81; 2.60-8.91), bladder (1.37; 1.14-1.65), and kidney (2.58; 2.14-3.11), as well as multiple myeloma (1.92; 1.51-2.44), and chronic myeloid leukemia (2.04; 1.26-3.29). Significantly decreased risk was observed for prostate cancer (OR 0.49, 95%CI 0.41-0.59). Of note, risk of cancer of the colon, liver, vagina, penis, and kidney, and chronic myeloid leukemia increased with duration of dialysis (p-trend&amp;lt;0.01). Additional analyses for histologic subtype will be presented. Conclusions: ESRD was associated with a slight overall elevation in cancer risk but much stronger increases for specific cancers. Increased risks for infection-related cancers (anogenital, liver, and stomach cancers) may reflect immunodeficiency. Excess risks were observed for malignancies (bladder and kidney cancers, myeloma) that could directly lead to ESRD or are related to such conditions. Associations with prostate and colon cancers could reflect cancer screening patterns. Further investigation of the biological pathways underlying the development of cancer in ESRD is needed. 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 5738.
Anterograde Degeneration of the Nigrostriatal Pathway Visualized by 123I-FP-CIT SPECT in a Patient With Artery of Percheron Infarction
Authors: Masashi Nakadate, Norikazu Miyamoto, Jay Starkey, Akira Toriihara, Ukihide Tateishi
Journal: Clinical Nuclear Medicine (2016)

123I-FP-CIT SPECT is widely used for diagnosis in patients with parkinsonism. Vascular parkinsonism usually has nonspecific findings from normal uptake to radiotracer decrease in the infarcted region. Infarction of the substantia nigra has been reported as a rare cause of vascular parkinsonism. We present a case of artery of Percheron infarction involving the substantia nigra unilaterally with ipsilateral reduction of striatal uptake on 123I-FP-CIT SPECT, suggesting anterograde degeneration of the nigrostriatal pathway. Infarction of the substantia nigra should be considered in cases of decreased striatal uptake with marked laterality on 123I-FP-CIT SPECT.
Isolation of<i>Blastomyces dermatitidis</i>in Soil Associated with a Large Outbreak of Blastomycosis in Wisconsin
Authors: Bruce S. Klein, James M. Vergeront, Robert J. Weeks, U. Nanda Kumar, George Mathai, Basil Varkey, Leo Kaufman, Robert W. Bradsher, James F. Stoebig, Jeffrey P. Davis
Journal: New England Journal of Medicine (1986)

In investigating six cases of blastomycosis in two school groups that had separately visited an environmental camp in northern Wisconsin in June 1984, we identified a large outbreak of the disease and isolated Blastomyces dermatitidis from soil at a beaver pond near the camp. Of 89 elementary-school children and 10 adults from the two groups, 48 (51 percent) of the 95 evaluated in September had blastomycosis. Of the cases, 26 (54 percent) were symptomatic (the median incubation period was 45 days; range, 21 to 106 days). No cases were identified in 10 groups that visited the camp two weeks before or after these two groups. A review of camp itineraries, a questionnaire survey, and environmental investigation showed that blastomycosis occurred in two of four groups that visited a beaver pond and in none of eight groups that did not. Walking on the beaver lodge (P = 0.008) and picking up items from its soil (P = 0.05) were associated with illness. Cultures of soil from the beaver lodge and decomposed wood near the beaver dam yielded B. dermatitidis. We conclude that B. dermatitidis in the soil can be a reservoir for human infection.
Abstract 1553: Down-expression of ATM gene and protein associated with canine breast tumors.
Authors: Talita Mariana Morata Raposo, Renata C. Bueno, Márcio de Carvalho, Carlos E. Fonseca-Alves, Mirela Tinucci-Costa, Andrigo B. De Nardi, Silvia R. Rogatto, Renée Laufer-Amorim
Journal: Cancer Research (2013)

Abstract Background: Ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair that plays an important role in the maintenance of genome integrity. ATM transcript and protein down-regulation have been reported in sporadic breast carcinomas and the absence of ATM protein expression was also significantly associated with distant metastasis in women, but the mechanisms involved in the ATM deregulation are not well established. Aim: Due to the fact that mammary tumor biological behavior is similar between canine and humans, we evaluate ATM gene and protein expression in canine breast cancer and compared with normal mammary gland from dogs. Patients and methods: Fresh samples of non-metastatic (n=23) and metastatic mammary carcinomas (n=11) and normal breasts (n=10) were evaluated for ATM gene expression by RT-qPCR and from the same animals, another sample of tumor was collected, formalin-fixed and paraffin-embedded to assess ATM protein expression by immunohistochemistry. Evaluation of ATM protein expression was performed by the distribution of positively-immunostained tumor cells in scores: 1 (&amp;lt;25% cells positive), 2 (26% to 50% cells positive) and 3 (&amp;gt;51% cells positive). Results: Down expression of ATM was detected in tumors samples (non-metastatic and metastatic mammary carcinomas) when compared to normal breast samples (P= 0,0414). Additionally, scores 1 and 2 of ATM protein expression were exclusively observed in metastatic tumors presenting score 1: 18% (2 out of 11), score 2: 55% (6 out to 11) and non metastatic tumors presenting the same score 1 and 2: 17% (4 out to 23) while all normal breast tissues showed score 3 (P=0,0087). Conclusions: Down expression of ATM transcript was confirmed by ATM protein expression. Low levels of ATM suggest an involvement of DNA damage repair transcript and protein in tumorigenesis process of canine mammary tumors, as in women, corroborating for the use of dogs as a natural comparative model to study mammary gland tumors in humans. Citation Format: Talita Mariana Morata Raposo, Renata C. Bueno, Márcio de Carvalho, Carlos E. Fonseca-Alves, Mirela Tinucci-Costa, Andrigo B. De Nardi, Silvia R. Rogatto, Renée Laufer-Amorim. Down-expression of ATM gene and protein associated with canine breast tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1553. doi:10.1158/1538-7445.AM2013-1553
AB1329 Current and previous use of biologics in rheumatoid arthritis patients. Data from the norwegian biorheuma project:
Authors: G. Haugeberg, L. Bader, E. Rødevand, K. Haaland, C. Gjesdal, B. Storesund, H.C. Gulseth, E. Haavardsholm, K. Mikkelsen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Norway (4.9 million inhabitants) is among the countries with the highest proportion of patients with inflammatory joint disorders treated with biologic drugs (1). The total cost for biologic treatment in Norway has been estimated to be ∼800 million Nkr (∼105 million Euro) for rheumatoid arthritis (RA). In 1999 the first biologic drug, the TNF inhibitor Infliximab, became available for clinical use in Norway. In the following years other TNF inhibitors has become available (etanercept (2000), adalimumab (2004), certolizumab pegol (2010) and golilumumab (2010)) and other biologic treatments which includes IL-6 inhibition (tocilizumab 2009), T-cell inhibition (abatacept 2007) and B-cell depletion (rituximab 2006). <h3>Objectives</h3> To explore which biologic drugs RA patients were currently using, or had been using, assessed by the end of 2011 in Norway. <h3>Methods</h3> In 2009 the BIORHEUMA project (BIOlogic treatment of patients suffering from inflammatory RHEUMAtic disorders in Norway) was established. The aim was 1. To implement the use of outcome measures and the T2T recommendations in daily clinical practice by the use of a designated computerized system. 2. To obtain unselected real life data on clinical status and treatment practices in patient with inflammatory rheumatic joint disorders. All participating centers had to use the GoTreatIT Rheuma computer software system (www.diagraphit.com) to monitor their patients on biologic treatment. By the end of 2011 nine out of the ten participating centers reported to have implemented the clinical standard of monitoring RA patients on biologics. <h3>Results</h3> In 2011 a total of 7206 RA patients had been assessed at the participating centers and registered in the computer system. Among them 2745 (38.1%) RA patients were registered as current users and a total of 3286 (45.5%) as ever users of biologic drugs. The distribution of current and previous use of the biologic drugs among ever users of biologics is shown in the table. Ever use of 1 biologic drug was seen in 56.9%, 2 biologics in 23.5%, 3 biologics in 11.3% and 4 or more biologics in 8.3%. <h3>Conclusions</h3> As expected TNF inhibitors are the most frequent used biologic drugs for treatment of RA patients in Norway, with etanercept being the most frequently used. Among the other modes of action Rituximab is the most frequently used biologic drug. <h3>References</h3> Jonsson Bet al. Eur J Health Econ. 2008 Jan;8 Suppl 2:S61-86. <h3>Disclosure of Interest</h3> G. Haugeberg Shareholder of: DiaGraphIT, Grant/Research support from: Supported by Roche, Pfizer, Abbott, L. Bader: None Declared, E. Rødevand: None Declared, K. Haaland: None Declared, C. Gjesdal: None Declared, B. Storesund: None Declared, H. C. Gulseth: None Declared, E. Haavardsholm: None Declared, K. Mikkelsen: None Declared
AB0659 Serum levels of high mobility group box 1 protein and its association with quality of life and psychological and functional status in patients with fibromyalgia.
Authors: P. Oktayoglu, M. Caglayan, M. Bozkurt, S. Em, D. Ucar, L. Yazmalar, N. Mete, K. Nas, O. Gezer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> High mobility group box 1 protein (HMGB1) is a proinflammatory cytokine. Previous studies have suggested that HMGB1 can play an important role in the pathogenesis of many rheumatic diseases. [1-3] <h3>Objectives</h3> The aim of the present study was to investigate the serum levels of high mobility group box 1 protein in patients with fibromyalgia (FM) and its association with quality of life, psychological and functional status in these patients. <h3>Methods</h3> Twenty-nine patients who met the 1990 American College of Rheumatology (ACR) criteria for the classification of FM and twenty-nine healthy controls (HC) were enrolled to the study. Serum samples of patients and HC were collected and HMGB1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Fibromyalgia Impact Questionnaire (FIQ) was used to assess disease severity and functional status of patients with FM. The quality of life of the all subjects were assessed by Nottingham Health Profile (NHP) and depression and anxiety symptoms were evaluated by using the Hospital Anxiety and Depression Scale (HADS). <h3>Results</h3> HMGB1 protein levels were positively correlated with FIQ scores in patients with FM (p=0.002). However mean serum HMGB1 levels in patients with FM (0.711±0.391 ng/ml) were higher than HC (0.651±0.390 ng/ml), no significant difference was seen between two groups (p=0.474). <h3>Conclusions</h3> HMGB1 protein may be a good laboratory sourced candidate for the assessment of functional status and disease severity in patients with FM. <h3>References</h3> -Taniguchi N, Kawahara K, Yone K et al. High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum. 2003; 48, 971-981 -Chun yun ma Ma C, Jiao Y, Zhang J et al. Elevated plasma level of HMGB1 is associated with disease activity and combined alterations with IFN-alpha and TNF-alpha in systemic lupus erythematosus. Rheumatol Int 2012; 32, 395-402 -Ek M, Popovic K, Harris HE, Naucler CS, Wahren-Herlenius M. Increased extracellular levels of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in minor salivary glands of patients with Sjogren’s syndrome. Arthritis Rheum 2006; 54, 2289-2294. <h3>Disclosure of Interest</h3> None Declared
Abstract SY12-03: Multi-tumor analysis of TCGA data identifies expression commonalities across tumor types.
Authors: Katherine A. Hoadley, Cheng Fan, Matthew D. Wilkerson, Lisle E. Mose, Stuart R. Jefferys, J. Todd Auman, Joel S. Parker, D. Neil Hayes, Charles M. Perou
Journal: Cancer Research (2013)

Abstract High dimensional assays, such as DNA microarrays for gene expression, have helped delineate the complexity and diversity of most major cancer types. The Cancer Genome Atlas (TCGA), with its goal to comprehensively genomically characterize over twenty different types of tumors, gives us a wealth of data to start looking at similarities across tumor types. Much of the current data is now generated using Massively Parallel Sequencing (MPS) approaches, which yields tens of millions of “reads” per sample. Illumina Hiseq-based mRNA-sequencing data for twelve tumor types representing over 3,500 samples were analyzed for patterns unique to each tumors, and patterns present across multiple tumor types. Tumor types tested included rectal adenocarcinoma, colon adenocarcinoma, lung squamous cell carcinoma and adenocarcinoma, uterine corpus endometrial carcinoma, ovarian serous cystadenocarcinoma, kidney clear cell, breast ductal and lobular carcinoma, glioblastoma multiforme, bladder carcinomas, acute myeloid leukemia, and head and neck squamous cell carcinoma. Tissue-specific expression was the dominant signature; however, there were similarities across sets of tumors including a common “squamous” pattern that was populated by tumors from three distinct anatomic sites. Pathway or Module-based analysis also provided methods to comparisons across tissues. Cross tissue analysis of mRNA-seq data provides interesting observations of common tumor biology with potential insights into treatment. Citation Format: Katherine A. Hoadley, Cheng Fan, Matthew D. Wilkerson, Lisle E. Mose, Stuart R. Jefferys, J. Todd Auman, Joel S. Parker, D. Neil Hayes, Charles M. Perou. Multi-tumor analysis of TCGA data identifies expression commonalities across tumor types. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY12-03. doi:10.1158/1538-7445.AM2013-SY12-03
Single- versus double-balloon enteroscopy: the evidence base: Comment on Endoscopy essentials, Small-bowel endoscopy
Authors: P. Lenz, D. Domagk, P. Mensink, H. Aktas, M. Bretthauer
Journal: Endoscopy (2012)

Since the introduction of single-balloon enteroscopy (SBE) there has been an ongoing debate about its diagnostic yield and clinical impact in comparison with double-balloon enteroscopy (DBE). In the Endoscopy Essentials series, Andrea May recently published her interpretation of the current literature on small-bowel enteroscopy [1]. Her paper contains a number of statements that we would like to comment on.
Selection of a phase 3 dose regimen for denosumab based on pharmacokinetic (PK), pharmacodynamic (PD), and safety data from multiple subcutaneous (SC) dosing regimens in breast cancer patients (pts) with bone metastases (BM)
Authors: M. C. Peterson, G. Jang, W. Kim, E. Gurrola, A. Kinsey, R. Dansey
Journal: Journal of Clinical Oncology (2006)

3086 Background: Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation, function, and survival. PK and PD of denosumab (AMG 162), a fully human monoclonal IgG 2 antibody to RANKL, from a randomized, double-blind, active-controlled, multidose study in breast cancer pts with BM were evaluated and modeled to assist in dose selection for the pivotal phase 3 study. Methods: Five dosing cohorts (∼40/cohort) received 30-, 120-, or 180-mg denosumab SC Q4W; 60- or 180-mg denosumab SC Q12W. Data through 12 weeks were used for PK/PD modeling and dose decisions. Validated methods were used to quantify all serum and urine analytes. The bone resorption marker uNTx (reported as uNTx/Cr ratio) was used as the PD endpoint, and population PK/PD model parameters were estimated using nonlinear mixed effects modeling methods (NONMEM). A combination of PK/PD trial simulation (TS), clinical chemistries, and safety profiles was utilized for phase 3 dose selection. Results: Exposure to denosumab increased approximately dose-proportionally for both the Q4W and Q12W schedules, and accumulation (3 rd vs 1 st Q4W dose) ranged from 2.37- to 2.56-fold. The population typical half-maximal inhibitory concentration (IC 50 ) for denosumab to affect uNTx and the typical maximum suppression were estimated to be 12.2 ng/mL and 77.8%, respectively. While denosumab in all cohorts caused rapid and sustained suppression of uNTx from baseline (&gt;60%), TS showed that for a dose of 120 mg Q4W, 97% of subjects would be expected to attain denosumab serum concentrations above their individual IC 90 at steady state. TS did not suggest that higher doses (180 mg Q4W) would result in further uNTx suppression, and more asymptomatic decreases in calcium were noted in pts dosed above 120 mg Q4W. Conclusions: The PK and PD of denosumab in pts with BM are consistent with those in other pt populations and demonstrate rapid and substantial suppression of uNTx. Population PK/PD analysis and TS suggests a dose of 120mg Q4W is appropriate for use in a phase 3 program in this study population. [Table: see text]