tbuckley/cabot-search huggingface dataset:
Quantitative Microscopy of Epidermoid Lung Carcinoma: Correlation With Survival Time 2
Authors: B. Gerstl, S. Wong, R. Yesner
Journal: JNCI Journal of the National Cancer Institute (1976)

Quantitative microscopy, including morphometry of tumor, stroma, and necrosis was used for the prognostication of pulmonary carcinoma. This was supplemented by the mitosis: necrobiosis ratio, reciprocal of cell count, and number of “apoptosis” bodies. Data for 15 short-term (4–19 mo) and 8 long-term (32–132 mo) survivors with epidermoid carcinoma were expressed as indexes. The morphometric index averaged 106.8 for short-term and 156.1 for long-term survivors, respectively. Addition of the other three indexes resulted in an average of 171.4 for short-term and 318.5 for long-term survivors. Morphometric index and the necrobiosis: mitosis ratio were of greater significance than the other two indexes. Discriminatory function analysis based on the weighted sum of the logarithms of the four indexes demonstrated their usefulness in classifying patients as shortterm or long-term survivors. The error rate for the discriminant analysis was 3.5%.
PTH-165 Hexane extracts of calophyllum brasiliense inhibit the development of gastric preneoplasia in helicobacter felis infected ins-gas mice
Authors: L Lemos, F Miyajima, D Tabajara de Oliveira Martins, DM Pritchard, MD Burkitt
Journal: Gut (2015)

<h3>Introduction</h3> <i>Calophyllum brasiliense</i>is a tropical hardwood tree native to Latin America. Indigenous populations have used extracts from the stem bark of this tree to treat gastrointestinal symptoms for generations. In previous studies we demonstrated that a hexane extract of <i>Calophyllum brasiliense </i>stem bark (HECb) protects against an acidified ethanol model of gastric ulceration in Swiss-Webster mice. We hypothesised that HECb would also inhibit the gastric epithelial pathology, including gastric preneoplasia that is induced by <i>Helicobacter</i>infection. To investigate this we have used the established hypergastrinaemic INS-Gas, <i>H. felis</i>infection model. <h3>Method</h3> Groups of 6 male, 6 week old INS-Gas mice were colonised with <i>H. felis</i>by oral gavage. Between 2 weeks after colonisation and the end of the procedure their drinking water was supplemented with 2% Tween 20, HECb 83.3 mg/L (lHECb) or HECb 333.3mg/L (hHECb). Equivalent uninfected control groups were also studied. Animals were culled 6 weeks after <i>H. felis </i>colonisation. Gastric mucosal samples were taken for histology and protein extraction. Preneoplastic pathology was quantified using established histological criteria. Gastric epithelial cell turnover was quantified by immunohistochemistry for Ki67 and active-caspase 3. Cytokines were quantified using electrochemiluminescence assays. <h3>Results</h3> <i>H. felis </i>infected mice treated with Tween 20 exhibited increased gastric atrophy scores than uninfected mice treated with Tween 20 (mean atrophy score 5.6+/-0.87 SEM vs 2.2+/-0.58<i>, </i>p &lt; 0.01). The same pattern was observed following lHECb. Following hHECb, atrophy scores were lower in infected mice, and no significant difference was observed between these infected and uninfected mice (4.0+/-0.45 vs 1.8+/-0.86). Gastric epithelial apoptosis was not altered by <i>H. felis </i>or HECb administration. Compared to uninfected mice, gastric epithelial cell proliferation was increased 2.8 fold in infected, Tween 20 treated mice (p &lt; 0.01). Administration of either lHECb or hHECb reduced proliferation indices to similar levels seen in uninfected mice. Cytokine evaluation demonstrated a T<sub>h</sub>17 polarised response to <i>H. felis</i>infection and decreased abundance of IFN-γ, IL-6 and TNF in the infected mice administered hHECb (70% (p &lt; .01), 67% (p &lt; .01) and 41% (p &lt; 0.05) reduction <i>vs </i>Tween 20 respectively). <h3>Conclusion</h3> HECb modulates gastric epithelial pathology following <i>H. felis </i>infection in INS-Gas mice. The extract influences both epithelial cell turnover and cytokine production. Further studies are indicated to dissect the mechanisms underlying these observations, and to identify the biologically active constituents of HECb. <h3>Disclosure of interest</h3> None Declared.
Clinical Pharmacokinetics
Authors: David J. Greenblatt, Jan Koch-Weser
Journal: New England Journal of Medicine (1975)

Modes of AdministrationAlthough drugs such as aminophylline, diazoxide, furosemide and lidocaine are actually administered by rapid intravenous injection, other modes of drug administration are obviously more common. All present special pharmacokinetic challenges and opportunities.Continuous Intravenous InfusionMany clinically important drugs are often given by intravenous infusion. They include aminophylline, isoproterenol, lidocaine, nitroprusside, norepinephrine, trimethaphan, and sometimes heparin. The pharmacokinetics of a constant-rate infusion12,13 can be described by modification of Equation 1 to include the rate of drug infusion (Q) into the central compartment: Solving the two simultaneous differential equations (Equations 2 and 13) . . .
AB0263 Clinical Onset and Squeezing Test Positivity Influence the Probability to Achieve Clinical Remission at 12 Months in Patients with Early Arthritis
Authors: G. Crepaldi, C.A. Scirè, G. Sakellariou, S. Bugatti, F. Benaglio, R. Caporali, C. Montecucco
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Early diagnosis and prognostic stratification are central issues in the management of early arthritis and rheumatoid arthritis (RA), with several baseline features affecting relevant outcomes <sup>1,2</sup>. <h3>Objectives</h3> To evaluate the influence of referral criteria and pattern of joint involvement on the achievement of DAS28 remission at 12 months in patients with early arthritis. <h3>Methods</h3> Consecutive patients attending an early arthritis clinic between 2005 and 2013 were enrolled. Referral criteria included joint stiffness&gt;30 minutes, joint swelling and positive squeezing test (ST) at metacarpophalangeal or metatarsophalangeal joints. Baseline demographic features, disease activity, symptom duration and pattern of symptom onset (inflammatory pain, joint stiffness, monoarthritis, oligoarthiritis or polyarthritis) were recorded. Patients classified as RA were treated with methotrexate, while patients with undifferentiated arthritis with hydroxichloroquine. Low-dose oral prednisone could be given. Patients were subsequently treated according to a DAS28 driven step-up protocol in order to achieve low disease activity<sup>3</sup>, they were seen every 2 months in the first six months and every 3 afterwards, DAS28 was recorded at each evaluation. The outcome of interest was clinical remission (DAS28&lt;2.6) occurring within the first 12 months of follow-up. Analyses on remission were done using a Cox proportional hazard regression analysis, results presented as crude hazard ratios (HR) and 95% confidence intervals (CI) and adjusted for age, gender, symptom duration at presentation, rheumatoid factor and/or ACPA positivity, baseline DAS28, use of steroids and MTX dose. <h3>Results</h3> A total of 772 patients were included. Mean age (SD) was 57.78 (14.94) years, 73.06% were female, 36.9% had positive rheumatoid factor, 68.6% fulfilled the 2010 criteria for RA, mean DAS28 was 4.60 (1.23) median (IQR) symptom duration was 15.1 (8.8-28.8) weeks (IQR). 72.7% were referred for positive ST, 66.7% for joint effusion, 56.5% for stiffness. 56.7% of patients presented with polyarthritis, 17.3% with inflammatory pain, 15.3% with oligoarthritis, 4.8% monoarthritis, 3.8% stiffness, 1.8% other presentation. The influence of referral criteria and clinical onset on remission achievement at 12 months is collected in Table 1. <h3>Conclusions</h3> Patients referred for ST positivity are less likely to achieve remission at 12 months than patients referred for swelling or stiffness. Similarly patients with oligoarticular or polyarticular onset achieve remission less frequently. <h3>References</h3> Symmons DP et al, J Rheumatol. 1998;25(6):1072-7. Machold KP et al, Rheumatology 2007;46:342–349. Sakellariou G. et al, Ann Rheum Dis 2013;72:245-9. <h3>Disclosure of Interest</h3> None declared
PTU-115 What is required for control and elimination of hepatitis B globally?
Authors: S Nayagam, M Thursz, S Wiktor, D Low-Beer, T Hallett
Journal: Gut (2015)

<h3>Introduction</h3> Despite the availability of a safe and effective vaccine and treatment against hepatitis B, variability of coverage means that HBV still accounts for up to one million deaths annually worldwide. Our aim was to evaluate and support the potential impact of scaling up interventions against HBV, set realistic targets for elimination of transmission and mortality due to HBV and identify key developments needed to achieve them. <h3>Method</h3> A dynamic, age, sex and region-structured mathematical model of the worldwide HBV epidemic was constructed incorporating data on epidemiology, vaccination coverage, treatment, regional demography and the natural history of HBV. The model was used to generate predictions regarding incidence of new chronic HBV infections, prevalence and HBV related mortality under assumptions that interventions remain at current levels (‘status quo’). We then used the model to estimate the impact of scaling up of both prevention and treatment interventions, to establish what would be sufficient to bring HBV to the threshold of control and elimination by 2030. <h3>Results</h3> The scale-up of infant HBV vaccination to date, is already driving a decrease in new infections, and if maintained at current levels, will have averted 1.2 M deaths by 2030. This will also result in a greater proportion of transmission being mother-to-child. Without further intervention, the number of persons living with HBV will remain at the same current high levels for the next 40–50 years and there will be 20 M HBV-related deaths by 2030. However, a 90% reduction in incidence of new chronic infections and 65% reduction in mortality could be achieved by 2030 with the scale-up of existing interventions: &gt;95% coverage of infant vaccination, 80% coverage of birth dose vaccine and 73% coverage of treatment for all those eligible (implemented from c. 2020). This would amount to 13 M deaths averted worldwide by 2030, including 6 M cases of cancer. The global cost is forecast to peak at $7.5 B annually but decline rapidly after 2030, and could be accelerated if a cure is developed. <h3>Conclusion</h3> The fight against HBV through universal infant vaccination has scored major victories in reducing new infections in some settings but, without further intervention, prevalence and mortality will remain high for decades. However, expansion of vaccination and treatment could reduce deaths by 65% and transmission by 90%. Although the costs are high, they peak at lower values and decline more rapidly than those projected for other infectious diseases with similar burden. <h3>Disclosure of interest</h3> None Declared.
Treatment of Familial Hemophagocytic Lymphohistiocytosis With Bone Marrow Transplantation From HLA Genetically Nonidentical Donors
Authors: Nada Jabado, Elizabeth R. de Graeff-Meeder, Marina Cavazzana-Calvo, Elie Haddad, Françoise Le Deist, Malika Benkerrou, Rémi Dufourcq, Sophie Caillat, Stephane Blanche, Alain Fischer
Journal: Blood (1997)
SAT0358 Pregnancy Outcomes Among Women with Chronic Inflammatory Arthritis or Psoriasis Treated and Not Treated with Etanercept (ENBREL) During Pregnancy: Table 1.
Authors: N.A. Accortt, W.J. Carman, C. Enger, J. Iles, M.S. Anthony
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Limited population-based data are available regarding the safety of etanercept (ETN) use during pregnancy. <h3>Objectives</h3> The purpose of this study was to describe the prevalence of pregnancy outcomes among women with chronic inflammatory arthritis (cIA) or psoriasis (PsO) with or without ETN exposure during pregnancy and among a non-disease, non-ETN control group. <h3>Methods</h3> Using administrative claims data from 1995 through June 2012, we identified pregnant women with cIA (defined using ICD-9 codes as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis or ankylosing spondylitis) or PsO treated with ETN or not treated with any tumor necrosis factor inhibitor (TNFi) during pregnancy. A general population control group with no evidence of cIA or PsO and no TNFi treatment during pregnancy was frequency matched (5:1 ratio) to the ETN cIA or PsO groups for age and year of pregnancy. The prevalence of pregnancy outcomes (live birth, stillbirth, spontaneous abortion (SA), premature delivery) was calculated among 6 cohorts. A sample of medical charts was abstracted to verify the pregnancy outcome data identified by the claim. <h3>Results</h3> We identified 4,883 pregnancies leading to 3,523 (72.1%) live births. There were 896 (18.3%) women with claims for miscarriages, ectopic pregnancies or spontaneous abortion, 433 (8.9%) with claims for non-spontaneous, therapeutic, elective, or unspecified (TEU) abortions and 45 (0.9%) with claims for stillbirths. The prevalence of these outcomes varied little between cohorts (Table). The prevalence of premature delivery was similar among the cIA cohorts (exposed and unexposed) but higher than the general population. In our sample of 300 medical charts, outcome data were available for 236 (64 received charts had no pregnancy outcome data) and confirmed 98% of the live birth claims and 100% of the non-live birth claims. <h3>Conclusions</h3> Pregnancy outcomes were comparable among cIA and PsO cohorts of women exposed to ETN or not exposed to any TNFi during pregnancy and general population controls. <h3>Acknowledgements</h3> Study funded by Immunex, a wholly owned subsidiary of Amgen Inc. and through a research contract between Amgen, Inc and Optum, Epidemiology <h3>Disclosure of Interest</h3> N. Accortt Shareholder of: Amgen, Employee of: Amgen, W. Carman Shareholder of: United Health Group, Employee of: Optum, C. Enger Shareholder of: United Health Group, Employee of: Optum, J. Iles Shareholder of: Amgen, Employee of: Amgen, M. Anthony Shareholder of: Amgen
Surveying the new Allergic and hypersensitivity conditions chapter of the International Classification of Diseases (<scp>ICD</scp>)‐11
Authors: L. K. Tanno, M. A. Calderon, N. G. Papadopoulos, M. Sanchez‐Borges, H.‐B. Moon, J. C. Sisul, E. J. Jares, J. L. Sublett, T. Casale, P. Demoly
Journal: Allergy (2016)

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FRI0228 Paradoxical Articular Manifestations in Inflammatory Bowel Diseases Patients Treated by Anti-TNF
Authors: P. Lasselin, H. Thiebault, V. Goeb, Jean-Louis Dupas, Mathurin Fumery
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Articular manifestations are the most common extra-intestinal manifestations associated to inflammatory bowel diseases (IBD). They are named "paradoxical" when they occur during treatment, notably anti-TNF drugs, that are expected to prevent or at least treat them. <h3>Objectives</h3> The aim of this study was to assess the frequency, the characteristics and the associated factors of paradoxical articular manifestations during anti-TNF treatment for IBD. <h3>Methods</h3> In this prospective single-center study, a rheumatological examination was systematically proposed to all IBD patients treated with infliximab (IFX) or adalimumab (ADA) to assess the prevalence of articular manifestations and distinguish those related to IBD treatment of those associated with IBD. Paradoxical manifestations were defined by the occurrence of articular manifestations (excluding induced-lupus and hypersensitivity reaction) during anti-TNF therapy in a patient in IBD intestinal remission. Dosage of biological inflammatory (WBC, ESR,CRP) immunological markers (immunoglobulins, anti-nuclear antibody (Ab), anti-DNA Ab, anti-CCP Ab, complement factor, rheumatoid factor, ASCA) and HLA-B27 allele and through serum IFX and anti-IFX Ab were systematically performed. <h3>Results</h3> Between May 2013 to April 2014, 79 patients with Crohn9s disease (CD) and 20 ulcerative colitis (UC) treated with IFX (n=80) or ADA (n=19) were included. Immunosuppressors (azathioprine/methotrexate) were associated in 12% of cases. Articular manifestations were observed in 50 (62%) patients treated by IFX and 12 (63%) patients treated by ADA. Twelve percent (n=12) were considered associated to IBD and 16% (n=16) associated to anti-TNF therapy. Among patients with articular manifestations associated to anti-TNF therapy, we identified 12% (n=12) of paradoxical effects, 2% (n=2) of induced lupus and 2% (n=2) of hypersensitivity reaction. Among the 12 patients with paradoxical effects during IFX (n=9) or ADA (n=3) therapy, 11 were treated for CD and presented peripheral arthritis; 3 patients presented a spondyloarthropathy. Paradoxical cutaneous manifestations (psoriasis) were associated in 25% of cases. The median duration of anti-TNF therapy was 47 months (Q1=30-Q3=77). No patient has discontinued anti-TNF because of the articular manifestations. Three patients were treated with methotrexate. No clinical or biological factors were associated with the occurrence of paradoxical manifestations. <h3>Conclusions</h3> Paradoxical articular manifestations in IBD patients treated by anti-TNF are common, affecting more than 10% of patients. These events are generally mild and not followed by the discontinuation of anti-TNF drugs <h3>Disclosure of Interest</h3> None declared
Daily set up variation in patients receiving radiation with tomotherapy for lung tumors
Authors: N. Mohammed, M. P. Mehta, S. M. Bentzen, D. Khuntia, W. A. Tome
Journal: Journal of Clinical Oncology (2006)

17005 Background: The on-board megavoltage (MV) computed tomography (CT) capabilities of a Tomotherapy unit were used to obtain the daily MVCT images of lung cancer patients. For daily patient alignment, differences between the MVCT scan and planning CT were resolved by calculating the necessary couch shifts in the X = mediolateral, Y = craniocaudal, and Z = anteriorposterior directions. Daily shifts were analyzed. Methods: 583 alignments from 36 patients with lung cancer were available for analysis. The systematic (Σ) and random (σ) errors were calculated and a covariate analysis was performed with tumor size, Karnofsky Performance Score (KPS), and presence of atelectasis. Two error minimization strategies were applied to the data - 1) shifts from fraction 1 were subtracted from subsequent shifts, and 2) the average of shifts 1–3 were subtracted from shifts 4 onward. Σ and σ were calculated for each of the 3 data sets and applied to van Herk’s margin recipe 2.5 Σ + 0.7σ. The mean, standard deviation, and standard error of the magnitude shifts for 13 patients who each received 23 fractions were analyzed by Spearman’s rank correlation test for the relationship between shift magnitude and fraction number. Results: The presence of atelectasis was significantly related to a smaller σ in millimeters, 2.8 ± 0.08 vs. 3.5 ± 0.09 (p = 1.1 × 10 −8 ). The other covariates were not significantly related to set-up error. The 2 nd error minimization strategy decreased Σ in the X, Y, and Z directions from 4.7 ± 0.6, 5.8 ± 0.9, 4.9 ± 0.6 to 2.1 ± 0.1, 4.2 ± 0.5, 3.4 ± 0.3 (p = 2.0 × 10 −5 , 0.13, 0.02) respectively. Calculated margins from van Herk’s equation for all data reported as (x, y, z) in mm were (13.8, 19.6, and 15.9). For strategies 1 and 2 respectively, calculated margins were reduced by (27.2%, 11.5%, 10.6%) and (46.7%, 21.5%, 23.2%). The mean magnitude of isocenter shift and the standard deviation were found to increase with fraction number (p = 1.0 × 10 −6 and 5.0 × 10 −5 respectively). Conclusion: The error correction strategies significantly reduced Σ but did not reduce the margins dramatically. Drift in accuracy during a long treatment course and an inability to identify subgroups of patients based on our covariates who may not need daily imaging suggests that daily image verification + correction will help reduce error and margins. No significant financial relationships to disclose.
Hedgehog signaling correlates with hepatocellular carcinoma progression
Authors: J. K. Sicklick, A. Jayaraman, R. Kannangai, M. S. Torbenson, M. A. Choti, A. M. Diehl
Journal: Journal of Clinical Oncology (2005)

9610 Background: Hedgehog (Hh) pathway activation promotes foregut tumors, such as pancreatic cancer. Whether Hh activity modulates hepatocellular carcinoma (HCC) pathogenesis is unknown. Although mature hepatocytes do not express the pathway, liver development requires Hh signaling. Blocking Hh prevents hepatogenesis and promotes pancreatic differentiation, suggesting a common precursor for liver and pancreas. The Hh pathway is activated when Sonic (Shh) or Indian (Ihh) ligands bind to the receptor, Patched (Ptc). When unoccupied by ligand, Ptc is a tumor suppressor because it binds Smoothened (Smo), an oncogenic protein, preventing Smo from activating Gli1. When ligand binds to Ptc, Smo is released and activates Gli1, which induces the transcription of its target gene, Ptc. Thus, Ptc mRNA levels increase with Hh activity. Aim: Determine if mRNAs of tumor suppressor (Ptc) or oncogenic (Shh, Ihh, Smo, Gli1) Hh pathway components are altered in human HCC. Methods: Total RNA was extracted from HCC and non-cancerous livers of 12 adults with HCC and various chronic liver diseases (alcoholic 8%, viral 50%, cryptogenic cirrhosis 25%). Two-step real-time PCR was done to compare expression of Shh, Ihh, Ptc, Smo, and Gli1 in HCC and non-tumor tissue from each patient. *p<0.05. Results: HCC ranged from 1–11 cm (mean 4±3 cm). The oncogenic factor, Smo, averaged >2-fold increase in the HCCs compared to non-tumorous liver. Regression analysis demonstrated that Smo mRNA levels correlated with HCC size*. In 8/12 (67%) HCCs, expression of the tumor suppressor, Ptc, was also significantly different than that of non-cancerous liver: 6 HCC had a 3× decrease, while 2 had an 11× increase in Ptc mRNA. Tumors with decreased Ptc were larger than HCC with normal expression (5±4 v. 3±1 cm)*. Serum levels of α-fetoprotein were barely elevated in any patient (mean 6.4±4.3 ng/mL) and did not correlate with HCC size or expression of Hh signaling components. Conclusion: Human HCCs have altered expression of Hh pathway components that regulate development of the liver from endodermal precursors. Although this pathway has been implicated in carcinogenesis of other endodermally-derived tissues, this is the first evidence for altered Hh pathway activity in hepatocarcinogenesis. No significant financial relationships to disclose.
CO2 challenge of patients with panic disorder
Authors: M R Fyer, J Uy, J Martinez, R Goetz, D F Klein, A Fyer, M R Liebowitz, J Gorman
Journal: American Journal of Psychiatry (1987)

In an open trial, five of eight panic disorder patients and none of five control subjects panicked after inhalation of two breaths of 35% CO2 and 65% O2; none panicked after placebo. Using 35% CO2 to induce panic is safe, simple, and well tolerated and may provide a valuable laboratory model of panic.