tbuckley/cabot-search huggingface dataset:
PWE-081 Comparison of elective and emergency cholecystectomies – a longitudinal cohort study with focus on inpatient stay
Authors: J Spence, Y Sinha, Z Zafar, F Iqbal, C Cheruvu, V Rao
Journal: Gut (2015)

<h3>Introduction</h3> Emergency cholecystectomy during index admission has become a standard of care in all major acute surgical units. However, with competing interests for emergency theatre time, the duration of inpatient stay has become a frustrating experience both for the surgical team and the patient. <h3>Method</h3> A prospective longitudinal cohort study including all consecutive patients who underwent emergency and elective cholecystectomies over a six month period in a busy tertiary centre was undertaken. Demographic data, inflammatory markers, number of inpatient days and post op complications were analysed. In addition, number of previous admissions among patients waiting for elective cholecystectomies was analysed. Statistical tests including one way ANOVA and unpaired T test were used when appropriate. <h3>Results</h3> 145 patients (Age: 50; range:16–85, M:F = 44:101) were admitted on an emergency basis and 161 patients (Age 51; range: 17–84, M:F= 36:125) were admitted to undergo elective cholecystectomies as day case procedure over a six month period. Based on intra-op findings, three subgroups of patients among emergency admissions were identified: biliary colic with thin walled gall bladder (n = 51; 13 with pancreatitis), acute cholecystitis with inflamed thick walled gall bladder (n = 78; 22 with pancreatitis) and complicated cholecystitis with empyema and perforation (n = 16). There was a significant difference in mean CRP and WCC levels (biliary colic: 21.9 and 9.4, acute cholecystitis: 85.1 and 11.7, complicated cholecystitis: 181.4 and 13.9, p = 0.000 and p = 0.002; one way ANOVA). There was a significant difference between the number of days between admission to operation for emergency (n = 145) and elective cases (n = 161) (4.1 vs 0, p = 0.000), and number of inpatient days for emergency (n = 145) and elective cases (n = 161) (6.6 vs 1.0, p = 0.000; unpaired T test). If the patients who had biliary colic and acute cholecystitis (excluding patients who had pancreatitis) were treated on an outpatient basis, a potential saving of 594 inpatient days could be done. Among patients who underwent elective cholecystectomies, 35 patients had A&amp;E/acute admissions during the waiting period (149 days; range: 11–983). Majority of this subgroup of patients (n-27) waited for more than 50 days, implying that a second encounter with emergency services can be avoided if these patients get their elective surgery within this time period. <h3>Conclusion</h3> Majority of emergency patients presenting with acute gall bladder symptoms can be managed on an outpatient basis with definitive surgery planned on a day case basis. This will save a significant number of inpatient days with obvious implications at a time of increasing bed pressures in the NHS. <h3>Disclosure of interest</h3> None Declared.
Gastric cancer (GC) in California Cancer Registry (CCR): One disease, many faces.
Authors: Afsaneh Barzi, Mariana C. Stern, Juanjuan Zhang, Heinz-Josef Lenz, Syma Iqbal, Lihua Liu
Journal: Journal of Clinical Oncology (2014)

30 Background: In the US there are approximately 21,000 newly diagnosed GCs with California having the highest number of reported cases per year. Given the disparity in the incidence of the disease among Asians and Hispanics we conducted an analysis of GCs in the CCR to assess the differences in the presentation and outcome of the reported cases from 2000 to 2010. Methods: We identified 26,645 GCs inclusive of Asian, Hispanic, and non-Hispanic whites (NHW); 20% of our population is Asian and 30% of is Hispanic. We examined the tumor characteristics (demographics, stage, anatomical subsite), age adjusted incidence rates (AAIR), and survival among Asian and Hispanic patients as compared to NHW. Results: AAIR per 100,000 individuals is 5.87 (95% CI: 5.77-5.97) for NHW, 11.74 (95% CI: 11.46-12.02) for Hispanics and 13.31 (95% CI: 12.96-13.66) for Asians. Among Asians, Koreans have the highest rate and lowest median age of presentation (67ys). In the patients with known stage of the disease (82%) most patients present with stage IV (38%) with no differences in the stage of presentation among different racial/ethnic groups. The male/female (M/F) ratio is different among different racial/ethnic groups. M/F among NHWs is 2.2, followed by 1.8 in Hispanics, and 1.6 in Asians. Among NHW proximal GC (cardia and fundus) is the most common site of presentation (44%), whereas in Asians and Hispanics proximal GC are reported in 14% and 18% respectively. Hazard ratios from Cox regression models adjusted for age, gender, socioeconomic status, nativity, stage, anatomical subsite, and type of treatment received, showed that being of Mexican origin is associated with greater risk of cancer death compared to being NHW (HR = 1.3; 95% CI = 1.2-1.4; p&lt;0.001). In contrast Koreans have better survival than NHW (HR = 0.9; 95% CI = 0.8-0.9; p=0.003). Prognostic factors for death from gastric cancer included age &gt; 65 and immigration status, with immigrants doing better than US born. Conclusions: The observed disparity in the incidence, presentation, and outcome of GC in CCR suggests possible different etiologies that may have implications for the diagnosis and treatment of GC and deserve further exploration.
Is capecitabine a cost-effective adjuvant treatment of stage III colon cancer in Ontario?
Authors: M. C. Orchard, J. S. Hoch, S. M. Alibhai
Journal: Journal of Clinical Oncology (2008)

15024 Background: The cost-effectiveness of capecitabine, as adjuvant treatment for Stage III colon cancer was explored. Phase III clinical trials show that capecitabine improves disease-free survival compared to standard care. However, these trials involved younger patients than reflected clinically and overall survival was not significantly better than with usual care. We conducted a modeling study comparing the cost-effectiveness of capecitabine and standard care (Fluorouracil/Leucovorin (5FU/LV)) in a public-payer context (Canada), using an older cohort, and with overall survival as the main outcome. Methods: A Markov model was developed to determine the cost-effectiveness of capecitabine compared with 5FU/LV. The base case was a 70-year-old man after total mesorectal resection excision of Stage III colon cancer. A 5-year time horizon was used. Health states included treatment phase, remission, recurrence, disease progression, and death; throughout the model (except during the active treatment states) patients could die from other risk-related causes. Ontario health economic data were used for costs. Probabilities were obtained from the published literature, and sensitivity analyses were conducted. Results: The base case costs for capecitabine and 5FU/LV were $12,999 and $12,191, respectively. Overall survival was 4.132 and 4.069 years, respectively. The incremental cost-effectiveness ratio of capecitabine was $12,821 per life year gained. However, the incremental cost-effectiveness ratio of capecitabine was greater than $50,000/life year when the annual probability of relapse was greater than 0.96 or when drug costs were assumed to be greater than $1,410 per cycle (both values within the plausible range). Conclusions: Capecitabine produced modestly improved survival over 5FU/LV (0.063 extra years) with a favourable cost-effectiveness ratio. However, because the model was sensitive to variations in relapse rate and drug costs, the relative attractiveness of capecitabine over 5FU/LV is not certain. In addition, utilities and indirect costs were not considered in the model. Because capecitabine is administered orally, this could be an important factor warranting further research. No significant financial relationships to disclose.
Prevalence and Clinical Impacts Of SETBP1 Mutation In East Asian Patients With MDS/MPN
Authors: Hyun-Woo Choi, Hye-Ran Kim, Hwan-Young Kim, Ju-Heon Park, Jae-Sook Ahn, Duck Cho, Seung-Jung Kee, Soo-Hyun Kim, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang, Myung-Geun Shin
Journal: Blood (2013)
Second Malignant Neoplasms After Treatment for Hodgkin’s Disease in Childhood or Adolescence
Authors: Daniel M. Green, Andrew Hyland, Maurice P. Barcos, Julie A. Reynolds, R. Jeffrey Lee, Brenda C. Hall, Michael A. Zevon
Journal: Journal of Clinical Oncology (2000)

To determine the frequency of and risk factors for second malignant neoplasms (SMNs) after treatment for Hodgkin's disease diagnosed in children and adolescents.One hundred eighty-two consecutive, previously untreated patients with Hodgkin's disease who were younger than 20 years of age at diagnosis and who were referred to Roswell Park Cancer Institute (Buffalo, NY) for treatment between January 1, 1960, and December 31, 1989, were studied. Sex-specific standardized incidence ratios (SIRs) were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to SMN incidence.Twenty-eight patients developed an SMN at a mean of 14.93 +/- 8.09 years (range, 2.65 to 29.88 years) after diagnosis of Hodgkin's disease. The cumulative percentage of patients who developed an SMN was 26.27 +/- 6.75% at 30 years after diagnosis. The SIR was 9.39 (95% confidence interval [CI], 4.05 to 18.49) for male patients and 10.16 (95% CI, 5.56 to 17.05) for female patients. The most frequent SMNs were thyroid cancer, breast cancer, nonmelanoma skin cancer, non-Hodgkin's lymphoma, and acute leukemia. Multivariate analysis of sex, treatment with any alkylating agent, treatment with doxorubicin, splenectomy, and relapse (as a time-dependent covariate) with time to SMN onset gave nonsignificant results.Successfully treated children and adolescents with Hodgkin's disease have a substantial risk for the occurrence of subsequent neoplasms. The most frequent SMNs (skin, thyroid, and breast) are readily detected by physical examination and available screening procedures.
M04-01: Severe dysplasia detected on AFB
Authors: Norihiko Ikeda, Hidetoshi Honda, Aeru Hayashi, Masatoshi Kakihana, Masahiro Tsuboi, Kentaro Iwasaki, Tatsuo Ohira, Takashi Hirano, Harubumi Kato
Journal: Journal of Thoracic Oncology (2007)
CT Features of Epidermal Growth Factor Receptor–Mutated Adenocarcinoma of the Lung: Comparison with Nonmutated Adenocarcinoma
Authors: Mizue Hasegawa, Fumikazu Sakai, Rinako Ishikawa, Fumiko Kimura, Hironori Ishida, Kunihiko Kobayashi
Journal: Journal of Thoracic Oncology (2016)
Reply
Authors: Eun Sung Park, Ju-Seog Lee
Journal: Hepatology (2013)

We thank Drs. Liu and Ye for their interest in our study.1 We appreciate their concern and would like to reiterate that the strength of our risk score, and its implication in the prognostication of hepatocellular carcinoma, is the result of unbiased systematic selection of a limited number of genes from a large number of genes in previously established prognostic signatures.2, 3 As Drs. Liu and Ye correctly pointed out, weak association of risk score with prognosis in data from Hoshida et al's study might have been the result of a difference in platform and sample sources.4 Our risk score was developed with data generated from frozen tissues. However, data from GSE10141 were generated by applying complementary DNA-mediated annealing, selection, extension, and ligation technology with the use of fragmented RNAs from formalin-fixed paraffin-embedded tissues. Moreover, the number of patients in their test set is smaller than our cohorts. Clinical data from one of the validation data sets (GSE14520) used in our study were recently updated and available as extra supplement data from the Gene Expression Omnibus. This data set would be better for the evaluation of different prognostication methods. However, we agree with them that new prognostication methods should be validated in a prospective study. EUN SUNG PARK, PH.D.1 JU-SEOG LEE, PH.D.2 1Institute for Medical Convergence, Yonsei University College of Medicine, Seoul, Korea 2Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Results cannot be generalised
Authors: S. Farrow
Journal: BMJ (1996)

Declining sperm countSemen quality has declined among men born in France since 1950 EDrroR,-Several recent papers have reported a possible decrease in sperm counts.`15Three of them were based on data collected in single laboratories, from a relatively low number of fertile men (between 302 and 1351).`-3Their conclu- sions were in favour of a decline related to the year of birth1 or to the year of the measurement3 or of no change.2The two other papers were reviews of the same published papers, the first concluding that sperm counts had decreased and
The prognostic importance of triple negative breast cancer: A population based study in India
Authors: B. S. Ajaikumar, R. Rao, J. Prabhu, J. D. Kulkarni, P. K, G. V Patil, N. Nr, C. Babu, R. Sahoo
Journal: Journal of Clinical Oncology (2009)

e22219 Background: Triple-negative (ER-negative, PR-negative, HER2/neu negative) breast cancer has distinct clinical and pathologic features, and is a clinical problem because of its typically high grade, relatively poor prognosis, aggressive behavior and lack of targeted therapies leaving chemotherapy as the mainstay of treatment. This study envisaged to analyse the influence of triple negativity status on survival and disease free survival in prospective cohort of breast cancer patients. Methods: Breast tumors of 215 women aged 30–75, diagnosed from 2004 were tested for ER, PR and HER2 positivity by immunohistochemistry and correlated with clinical outcomes such as recurrence, disease free survival and overall survival using Kaplan Meiers Survival analysis and Coxs regression analysis. The study cohort was followed up for 60 months or until death whichever was earlier. Results: Triple negativity significantly influenced disease free survival (46 ± 3, 41, 52) vs. non triple negative cohort (mean ± SE; 95%CI, 37 ± 2; 32, 40) and log rank = 2.1, p = 0.04. However triple negativity did not influence overall survival in months (56 ± 0; 55, 56) vs. non triple negative cohort (43 ± 1; 42, 45), (log rank = 1.78, p = 0.16). However, the mean disease free survival was (45 ± 7; 32, 58) months for patients &gt;40 years age vs (37 ± 4; 33, 39) for patients &lt; 40 years of age (log rank = 2.87, p =0.02). Stage of disease, node status, grade and menopausal status did not influence disease free survival significantly. However, Cox regression analysis did not predict significant effects of triple negativity on overall survival or disease free survival when controlled for confounding factors such as age, node status, stage etc Conclusions: Our observations suggest that triple negativity can significantly affect progression of breast cancer in Indian breast cancer patients and longer follow up is necessary (10 years) to determine its effects on survival. No significant financial relationships to disclose.
STUDIES ON HUMAN ANTIBODIES
Authors: Marianne M. Dorner, Emmett W. Bassett, Sam M. Beiser, Elvin A. Kabat, Stuart W. Tanenbaum
Journal: The Journal of Experimental Medicine (1967)

Human dextran-antidextran-specific precipitates from individuals immunized with dextrans containing either one or two antigenic determinants, were analyzed for their content of various amino acids. Large differences in certain amino acids were found among alpha-(1 --> 6)-specific antidextrans. Wide variations were also observed in antidextran fractions from a given individual specific for alpha-(1 --> 6)- and alpha-(1 --> 2)-linked glucose residues.
Activation &lt;italic&gt;In Vitro&lt;/italic&gt;, by 5-lododeoxyuridine, of a Latent Virus Resembling C-Type Virus in a Human Sarcoma Cell Line&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Sarah E. Stewart, George Kasnic, Jr., Catherine Draycott, William Feller, Abner Golden, Elisabeth Mitchell, Theresa Ben
Journal: JNCI Journal of the National Cancer Institute (1972)

A biopsy specimen of an undifferentiated human sarcoma contained particles resembling type-C particles of oncornavirus. Cultures of this neoplasm grew as spindle cells that after 8 weeks transformed to epithelioid-like cells with rounded cells that piled up and were shed into the culture fluid. Cells from cultures were devoid of virus-like particles on repeated electron microscopic examination. Attempts to activate a virus by cocultivation with normal human cells or by exposure to ultraviolet or X-ray irradiation failed to yield virus, as determined by electron microscopy or focus formation of normal cells with cell-free filtrates from the culture. However, when the cells were cultured in medium containing 5-iododeoxyuridine, budding particles resembling those formed by C-type oncornavirus were observed.
P64 Hepatitis B virus upregulates hepatocyte expression of PD-L1 to evade hepatoxic adaptive immune responses
Authors: S Phillips, A Evans, A Riva, R Williams, N Naoumov, S Chokshi
Journal: Gut (2010)

Introduction  Hepatitis B virus employs a variety of strategies aimed at overwhelming, evading or neutralising the host immune response to infection resulting in chronicity. We have previously shown that the Programmed Cell Death Pathway (PD-1/PD-L1) is an inhibitory T-cell pathway implicated in the homeostasis of immune responses and the balance between cytolytic and non-cytolytic CD8+ T-cell effector functions.  Aim  The aim of this study was to investigate the impact of hepatitis B virus (HBV) infection on hepatocytic PD-L1 expression.  Method  A human hepatoma cell line that constitutively expresses HBV-DNA (HepG2215), its parent cell line (HepG2) were cultured. A human hepatoma cell line (Huh7) was transfected with a plasmid containing an HBV head-to-tail dimer using Fugene 6 reagent. We also cultured a further HepG2 cell line (AD38) that produces full infectious virus under the control of a tetracycline (Tet)-responsive promoter. HBV-DNA and PD-L1 were quantitated longitudinally. Intracellular and secreted HBV-DNA was quantified with qRT-PCR. PD-1/PD-L1 expression was assessed by FACS and qRT-PCR. Co-cultures between virus-specific CD8+ T-cell lines and hepatocytes producing HBV were also established and analysis of T cell functions performed.  Results  The hepatoma cell lines which constitutively produce HBV virions (HepG2215) had significantly higher basal levels of PD-L1 expression compared with their parent cell line (HepG2) (p=0.01). A significant increase in intracellular and secreted HBV-DNA levels confirmed successful transfection of Hepatitis B virus. Following transfection there was a significant increase in PD-L1 levels (p=0.01) on infected hepatocytes, which was not observed following transfection with an empty vector. A significant correlation was observed between PD-L1 expression and both intracellular HBV-DNA (r=0.98, p=0.01) and secreted HBV-DNA (r=0.908, p=0.046) following transfection. Following activation of HBV-DNA expression in the AD38 cell line (-Tet), PD-L1 expression increased. Moreover, subsequent fluctuations in HBV-DNA in the absence/presence of Tet was temporally associated with the expression of PD-L1 (r=0.83, p  Conclusion  These results demonstrate that HBV-DNA drives PD-L1 expression on infected hepatocytes. As we have previously demonstrated, upregulation of PD-L1 impairs adaptive immune responses to HBV infection, and this novel function of HBV may reflect an important strategy by which hepatitis B virus extends the life-span of target hepatocytes and escapes an effective immune response contributing to the development of chronicity.
Efficacy of IFN-λ1 to protect human airway epithelial cells against rhinovirus 1B infection
Authors: Fahad Gulraiz, Erik V. Beuken, Gernot G. Rohde, Frank R. Stassen
Journal: European Respiratory Journal (2013)

Impaired interferon (IFNs) production has been observed in various respiratory diseases. This contributes to the enhanced sensitivity towards viral infections which ultimately lead to acute exacerbations. To compensate for this impaired host IFN response, there is need to explore new therapeutic strategies, like exogenous administration of IFNs as prophylactic treatment.  In the present study, we examined the protective potential of IFN-λ1 and compared it with the previously established protective effect of IFN-β. A549 cells and human primary bronchial epithelial cells were first treated with IFN-β (500IU/ml) and IFN-λ1 (500ng/ml) for 18h. For infection, two approaches were adopted: i) Continuous scenario: after pretreatment cells were infected with HRV for 24h or 72h in IFNs-containing medium, ii) Pre-treatment scenario: IFNs-containing medium was replaced after 18h cells were infected for 4h and further maintained for another 24h and 72h in HRV and IFNs-free medium. The protective effect was evaluated in terms of a reduction in the number of viral copies/infectious progeny, and an enhanced expression of IFN-stimulated genes (ISGs).  In both cell types and in both approaches IFN-β or -λ1 treatment resulted in pronounced and long lasting antiviral effects (even in the absence of the IFNs in the culture medium) exemplified by significantly reduced viral copy numbers and diminished infectious progeny. This was associated with strong up-regulation of multiple ISGs.  Here we demonstrate that protective potential of IFN-λ1 is comparable to IFN-β. Yet, due to the more localized expression of IFN-λ1 receptors (e.g. in the respiratory epithelium), the use of IFN-λ1 may be even more promising than IFN-β.
STAT4-associated natural killer cell tolerance following liver transplantation
Authors: K M Jamil, T J Hydes, K S Cheent, S A Cassidy, J A Traherne, J Jayaraman, J Trowsdale, G J Alexander, A-M Little, H McFarlane, M A Heneghan, M A Purbhoo, S I Khakoo
Journal: Gut (2016)

Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype.Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using gene expression analysis and donor:recipient HLA typing.NK cells from non-HCV LT recipients were hypofunctional, with reduced expression of NKp46 (p<0.05) and NKp30 (p<0.001), reduced cytotoxicity (p<0.001) and interferon (IFN)-γ secretion (p<0.025). There was no segregation of this effect with HLA-C, and these functional changes were not observed in individuals with HCV. Microarray and RT-qPCR analysis demonstrated downregulation of STAT4 in NK cells from LT recipients (p<0.0001). Changes in the expression levels of the transcription factors Helios (p=0.06) and Hobit (p=0.07), which control NKp46 and IFNγ expression, respectively, were also detected. Hypofunctionality of NK cells was associated with impaired STAT4 phosphorylation and downregulation of the STAT4 target microRNA-155. Conversely in HCV-LT NK cell tolerance was reversed, consistent with the more aggressive outcome of LT for HCV.LT is associated with transcriptional and functional changes in NK cells, resulting in reduced activation. NK cell tolerance occurs upstream of major histocompatibility complex (MHC) class I mediated education, and is associated with deficient STAT4 phosphorylation. STAT4 therefore represents a potential therapeutic target to induce NK cell tolerance in liver disease.