tbuckley/cabot-search huggingface dataset:
Balloon catheter versus basket catheter for endoscopic bile duct stone extraction: a multicenter randomized trial
Authors: Hirotoshi Ishiwatari, Hiroshi Kawakami, Hiroyuki Hisai, Kei Yane, Manabu Onodera, Kazunori Eto, Shin Haba, Toshinori Okuda, Hideyuki Ihara, Takehiro Kukitsu, Ryusuke Matsumoto, Keisuke Kitaoka, Tomoko Sonoda, Tsuyoshi Hayashi
Journal: Endoscopy (2016)

<b>Background and study aims:</b> Endoscopic bile duct stone (BDS) removal is a well-established treatment; however, the preference for basket or balloon catheters for extraction is operator-dependent. We therefore conducted a multicenter prospective randomized trial to compare catheter performance. <b>Patients and methods:</b> We enrolled patients with a BDS diameter ≤ 10 mm and common bile duct diameter ≤ 15 mm. Participants were randomly assigned to groups that were treated with basket or balloon catheters between October 2013 and September 2014. The primary endpoint was the rate of complete clearance of the duct; the secondary endpoints were the rate and time to complete clearance in one endoscopic session. <b>Results:</b> We initially enrolled 172 consecutive patients; 14 were excluded after randomization. The complete clearance rates were 92.3 % (72/78) in the balloon group and 80.0 % (64 /80) in the basket group. The difference in the rates between the two groups was 12.3 percentage points, indicating non-inferiority of the balloon method (non-inferiority limit −10 %; <i>P</i> < 0.001 for non-inferiority). Moreover, the balloon was superior to the basket (<i>P</i> = 0.037). The rate of complete clearance in one endoscopic session was 97.4 % using the balloon and 97.5 % using the basket (<i>P</i> = 1.00). The median times to complete clearance in one endoscopic session were 6.0 minutes (1 – 30) and 7.8 minutes (1 – 37) in the balloon and basket groups, respectively (<i>P</i> = 0.15). <b>Conclusions:</b> For extraction of BDSs ≤ 10 mm, complete endoscopic treatment with a single catheter is more likely when choosing a balloon catheter over a basket catheter. University Hospital Medical Information Network Trials Registry: UMIN000011887.
Abstract 9598: A Focused Heart Failure Self-Care Intervention Improves Self-Care Behavior Even in Patients with Global Cognitive Dysfunction
Authors: Debra K Moser, Michele M Pelter, Tom Nesbitt, Martha J Biddle, Susan Robinson, Jeffrey SOUTHARD
Journal: Circulation (2012)

Heart failure (HF) patients have high rates of global cognitive dysfunction (GCD). HF requires challenging levels of self-care for all, but may be particularly difficult for those with GCD. Objective: Determine the impact of tailored intervention focused on improving self-care of symptom management in HF patients with or without GCD. Methods: We randomized 614 (41.2% female; age 66 ± 13 years; 35.4% NYHA class III/IV) rural patients with HF to usual care or one of two active self-care symptom monitoring and management intervention groups (i.e., LITE and PLUS). Both intervention groups included tailored (to address individual barriers to self-care) education and counseling providing skills to recognize symptoms of escalating HF, tools to monitor symptoms and motivation to respond early. Intervention was delivered by an expert HF nurse. Intervention groups differed only in contact frequency; LITE group received two follow-up calls, while PLUS group received bi-weekly calls until judged trained. Cognitive function was assessed at baseline using the Mini-Cog; scores range from 0 to 6. Patients with overt dementia were excluded. GCD was defined as a score of 3 or 4. Self-care outcome data (HF Self-Care Behavior Scale) were collected at baseline, 3 and 12 months. Data were analyzed using repeated measures ANCOVA, controlling for age and education level. Findings: Of enrollees, 33.7% met criteria for GCD. Self-care improved in both intervention groups, but worsened in the usual care group (p &lt; 0.001 for group by time interaction). Patients with and without GCD demonstrated improvements in self-care when assigned to either of the intervention groups, but not the usual care group (Figure). Conclusion: Individualized intervention that includes focus on HF patients’ barriers to engaging in self-care is effective in improving self-care even in patients with GCD. A higher intensity of contact was not needed to achieve this effect.
Abstract 12021: Changes in Troponin I and Outcomes in Acute Heart Failure: Data from the Pre-RELAX study
Authors: G. Michael Felker, Marco Metra, Piotr Ponikowski, Adriaan A Voors, Barry Greenberg, Germasimos Filippatos, Elaine Unemori, Gad Cotter, Beth Davidson, Thomas Severin, Christopher Bush, Guenther Mueller-Velten, Rajnish Saini, John R Teerlink
Journal: Circulation (2012)

Background: Troponin I (cTnI) is a sensitive marker of myocardial injury and has been shown to be elevated in AHF. The clinical significance of changes in cTnI in patients with AHF is uncertain. Me...
Phase II trial of gemcitabine plus capecitabine in patients with advanced biliary tract cancer
Authors: H. M. Chang, M.-H. Ryu, J.-L. Lee, T. W. Kim, J. S. Lee, W. K. Kim, Y.-K. Kang
Journal: Journal of Clinical Oncology (2005)

4173 Background: Biliary tract cancer is a rare but aggressive cancer with median survival rarely exceeding 6 months. At present, there is no standard chemotherapy regimen for this disease. Recent trials suggest that new agents such as gemcitabine or capecitabine have activity in this disease. We conducted a phase II trial to evaluate the efficacy and toxicity of the gemcitabine plus capecitabine in patients with advanced biliary cancer. Methods: Patients with unresectable cholangiocarcinoma or gallbladder (GB) cancer who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS ≤ 2 and measurable disease were enrolled. Treatment consisted of gemcitabine 1,000 mg/m2 IV day 1, 8, 15 with capecitabine 830 mg/m2 PO BID day 1 to 21, on a 4 week cycle. Results: Between Dec 2002 and Sep 2004, 34 pts were enrolled. Median age was 52 (32–64) with 20 males. Twenty (59%) had cholangiocarcinoma, 11 (32%) had GB cancer and 3 (9%) had ampulla of Vater cancer. Thirty pts were evaluable for response and toxicity. A total of 88 cycles were administered (median, 2; range, 1–9). One patient achieved CR and 3 pts achieved PR giving an overall response rate of 11.8% in intention-to-treat population (95% CI, 1.0–22.6%). And 10 pts (29.4%) had stable disease. Response rate for cholangiocarcinoma is 15.0% and GB cancer is 9.1%. The median time to progression of all patients was 2.6 months (mo) (95% CI, 1.3–3.9). The median overall survival was 7.8 mo (95% CI, 6.5–9.0). Grade 3/4 neutropenia and thrombocytopenia were noted in 40.0% and 16.7% of the pts, respectively. Grade 2/3 non-hematologic toxicities were asthenia (36.7% of pts), diarrhea (10.0%), stomatitis (10.0%) and hand-foot syndrome (3.3%). There was no treatment-related death. Gemcitabine on days 8 and 15 was skipped/reduced in 8%/13%, and 23%/30% of the patients, respectively. Therefore, the dose intensity of gemcitabine fell to 88.6% and 66.6% of the planned dose on days 8 and 15, respectively.Conclusions: The combination of gemcitabine and capecitabine in this four week cycle does not seem to have advantages in activity over other regimens in advanced biliary cancer. New dose schedule which can maintain the dose intensity of gemcitabine may improve the activity of this combination. No significant financial relationships to disclose.
Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[ <i>a</i> ]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5- <i>b</i> ]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens
Authors: Rhiannon David, Timothy Ebbels, Nigel Gooderham
Journal: Environmental Health Perspectives (2015)

Chemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer. Individually, these compounds are genotoxic, but the consequences of exposure to mixtures of these chemicals have not been systematically examined.We determined the mutagenic response to mixtures of BaP and PhIP at concentrations relevant to human exposure (micromolar to subnanomolar).Human MCL-5 cells (metabolically competent) were exposed to BaP or PhIP individually or in mixtures. Mutagenicity was assessed at the thymidine kinase (TK) locus, CYP1A activity was determined by ethoxyresorufin-O-deethylase (EROD) activity and qRT-PCR, and cell cycle was measured by flow cytometry.Mixtures of BaP and PhIP produced dose responses different from those of the individual chemicals; we observed remarkably increased mutant frequency (MF) at lower concentrations of the mixtures (not mutagenic individually), and decreased MF at higher concentrations of the mixtures, than the calculated predicted additive MF of the individual chemicals. EROD activity and CYP1A1 mRNA levels were correlated with TK MF, supporting involvement of the CYP1A family in mutation. Moreover, a cell cycle G2/M phase block was observed at high-dose combinations, consistent with DNA damage sensing and repair.Mixtures of these genotoxic chemicals produced mutation responses that differed from those expected for the additive effects of the individual chemicals. The increase in MF for certain combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, as well as the nonmonotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers.David R, Ebbels T, Gooderham N. 2016. Synergistic and antagonistic mutation responses of human MCL-5 cells to mixtures of benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: dose-related variation in the joint effects of common dietary carcinogens. Environ Health Perspect 124:88-96; http://dx.doi.org/10.1289/ehp.1409557.
脾辺縁帯リンパ腫(SMZL)の治療におけるリツキシマブ併用または非併用2-CdAの有意な効果
Authors: G Cervetti, S Galimberti, E Sordi, G Buda, E Orciuolo, N Cecconi, M Petrini
Journal: Annals of Oncology (2010)
The in vivo immunomodulatory effects of recombinant interferon gamma plus recombinant tumor necrosis factor-alfa.
Authors: W J Urba, W C Kopp, J W Clark, J W Smith, R G Steis, C Huber, D Coggin, D L Longo
Journal: Journal of Clinical Oncology (1991)

We conducted a phase I study in which an intramuscular injection of interferon gamma (IFN gamma) at 10, 50, or 100 micrograms/m2 was followed 5 minutes later by an intramuscular injection of 10, 50, or 100 micrograms/m2 of tumor necrosis factor-alfa (TNF alpha) at another site every other day for 20 days (10 doses). The addition of TNF alpha to IFN gamma reduced both the magnitude and duration of IFN gamma-mediated effects on peripheral blood monocyte expression of Fc receptors (FcRs) and HLA-DR and production of hydrogen peroxide. This inhibition was related to the dose of TNF alpha. On the other hand, TNF alpha and IFN gamma appeared to have an additive stimulatory effect on the production of neopterin by monocytes. The highest serum levels of neopterin were detected in patients who received the highest doses of both IFN gamma and TNF alpha. Thus, conflicting conclusions regarding the effect of the combination on immune activation are possible. If the activation of peripheral blood monocytes is the appropriate surrogate measure of the immune enhancement of the combination, then the simultaneous administration of IFN gamma and TNF alpha is ineffective, and future attempts to exploit the potential additive or synergistic effects of this combination of cytokines in humans may need to explore sequential administration schemata. On the other hand, if serum neopterin levels are a more reliable index of immune activation, simultaneous administration of 100 micrograms/m2 IFN gamma and 50 micrograms/m2 TNF alpha every other day (the maximally tolerated dose [MTD]) should be used in phase II testing. This dilemma points out the limitations of currently available methods of human immune assessment and the inadequacies in our capacity to gauge what particular immune measure or set of measures predict for in vivo antitumor effects.
Runtastic PRO app: an excellent all-rounder for logging fitness
Authors: Antonio Monroy Antón, Bárbara Rodríguez Rodríguez
Journal: British Journal of Sports Medicine (2015)

<h3>Purpose</h3> The currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme. <h3>Participants</h3> All consecutive ≥18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually. <h3>Finding to date</h3> With a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and &gt;16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort. <h3>Future plans</h3> These real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings. <h3>Trial registration number</h3> NCT03275311; Pre-results.
Abstract 19279: Rescue Of D2R Function in Mouse Kidney Using AAV9 Vector Abrogates the Renal Injury and High Blood Pressure Induced by D2R Silencing
Authors: Prasad Konkalmatt, laureano D Asico, Yu Yang, Cinthia B Drachenberg, Pedro A Jose, Ines Armando
Journal: Circulation (2015)

In humans decreased dopamine D2 receptor (D2R) expression and function is associated hypertension and inflammation and fibrosis in renal proximal tubule cells. In mice selective D2R silencing in the kidney results in renal inflammation, injury and hypertension. We hypothesized that these alterations are ameliorated by rescue of renal D2R function. To test this hypothesis we silenced renal D2R expression by sub-capsular infusion of D2R siRNA (D2RsiRNA) using osmotic mini pumps (3 μg/day, n=6 per group). Mice treated with non-silencing siRNA (NS siRNA) served as controls. Two weeks after starting siRNA treatment, mice were treated with control AAV (CAAV) or AAV carrying wild-type D2R (D2RAAV) (n=3 per group, 1e+11 vgp/mouse). Two weeks following AAV treatment, blood pressure was measured and organs were collected. D2R expression was decreased in D2RsiRNA-treated kidneys compared with NSsiRNA-treated kidneys (54 ± 0.8 vs 100± 22 %; P&lt;0.05). D2RAAV treatment increased D2R expression (7.5-11-fold; P&lt;0.01) in both D2RsiRNA and NS siRNA-treated mice. Mice with silenced D2R expression (D2RsiRNA+CAAV) had increased systolic blood pressure (121±3 mmHg; P&lt;0.05) in comparison with the D2R rescued group ( D2RsiRNA+D2RAAV) (100±6 mm Hg), NSsiRNA+CAAV (101±4 mm Hg), or NS siRNA +D2RAAV (101±1 mm Hg). D2R silencing caused an increase in the expression of TNF-α, TGF-β1 and its downstream target fibronectin-1, as well as kidney injury molecule-1 and ki-67, a marker of cell proliferation. By contrast, the expression of these proteins was decreased or reversed to normal in the D2R-rescued group. Masson trichrome staining showed tubular atrophy, interstitial fibrosis and extensive areas of scaring in D2R silenced mice while these abnormalities were significantly reduced in the D2R rescued group. T cells infiltration was significantly higher in D2R silenced group compared to the D2R-rescued group (309 ± 38 vs 217± 17 %; P&lt;0.05). These results show that D2R re-expression prevented the progression of the lesions and demonstrate that increased blood pressure and renal injury due to D2R silencing could be rescued by over expression of D2R in the kidney using AAV9 vector. Furthermore, these data provide the basis for designing novel therapies for kidney disease.
Severe Hepatitis Promotes Hepatocellular Carcinoma Recurrence via NF-κB Pathway-Mediated Epithelial–Mesenchymal Transition after Resection
Authors: Ting-Jung Wu, Shih-Shin Chang, Chia-Wei Li, Yi-Hsin Hsu, Tse-Ching Chen, Wei-Chen Lee, Chau-Ting Yeh, Mien-Chie Hung
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Surgical resection is considered as a curative treatment modality for hepatocellular carcinoma; however, the incidence of postoperative tumor recurrence is high, leading to worse patient survival. Persistent hepatitis (inflammation) is one of the risk factors of tumor recurrence after surgical resection. The aim of this study is to investigate the underlying mechanisms linking liver inflammation to hepatocellular carcinoma progression. Experimental Design: In this study, we used a cytokine array to identify important cytokines whose levels are increased in liver microenvironment with severe hepatitis. We evaluated the morphologic changes, migration and invasion ability, and signal transduction in hepatocellular carcinoma cells with or without inflammatory cytokine in vitro. Finally, we analyzed the NF-κB signal pathway in tumor specimens from 232 patients with hepatocellular carcinoma by immunohistochemical staining. Results: The proinflammatory cytokine TNFα was increased in the peritumoral microenvironment and contributed to tumor recurrence and metastasis. Specifically, TNFα promoted hepatocellular carcinoma cancer cell migration, invasion, and epithelial–mesenchymal transition (EMT) by upregulating the transcriptional regulator, Snail. We identified Snail as a direct target gene downstream of the TNFα-mediated canonical NF-κB activation. In addition, tumor recurrence-free survival of hepatocellular carcinoma patients correlated negatively with high p65 and Snail expression and positively with high E-cadherin expression. Conclusions: Our results establish a signaling axis that explains how inflammatory tumor microenvironment promotes hepatocellular carcinoma recurrence and metastasis. These findings suggest that controlling liver inflammation and/or targeting NF-κB–mediated Snail expression may be a potential therapeutic strategy to prevent hepatocellular carcinoma recurrence after hepatectomy. Clin Cancer Res; 22(7); 1800–12. ©2015 AACR.
Press: The problem with medical advice columns
Authors: A. McPherson
Journal: BMJ (1999)

he story would make a marvellous soap opera.The research, into immunological genetics and published in Cell, is complex, made worse by the inadequate English of Teresa Imanishi-Kari, the Brazilian-Japanese research worker.Accused of fraud, she is defended by her charismatic but hubristic boss, the Nobel laureate David Baltimore, who takes on a congressional committee.The whistleblower, Margot O'Toole, a young Irish radical, loses her job, house, and career-but receives international honours and publicity for her courage.After 10 years and seven inquiries, reviews, and the final, successful, appeal, the US immunological
VTX-2337, a TLR8 agonist, plus chemotherapy in recurrent ovarian cancer: Preclinical and phase I data by the Gynecologic Oncology Group.
Authors: Bradley J. Monk, William E. Brady, Heather A. Lankes, Andrea Facciabene, Kristi Manjarrez, Robert Mark Hershberg, Paula M. Fracasso, Katherine M. Bell-McGuinn, Joan L. Walker, Carolyn K. McCourt, Carol Aghajanian, George Coukos
Journal: Journal of Clinical Oncology (2013)

3077 Background: Given the absence of clear molecular drivers in high-grade serous ovarian cancer, targeting the tumor micro-environment with immunotherapy is an emerging approach. VTX-2337 is a potent, small molecule agonist of TLR8 which stimulates the innate immune response, and was previously evaluated as a single agent in cancer patients. We report data combining VTX-2337 with chemotherapy in recurrent ovarian cancer. Methods: VTX-2337 was tested in an ovarian cancer mouse model with an intact human immune system. Additionally, an open-label phase I study of VTX-2337 + pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer (NCT01294293, N=13) was performed. PLD (40 mg/m 2 ) was given on day 1 of a 28-day cycle. Three dose levels of VTX-2337 (2.5, 3.0, 3.5 mg/m 2 , N=13) were serially tested and given by SC injection on days 3, 10, and 17. VTX-2337 (3.0 mg/m 2 ) was also tested with paclitaxel (80 mg/m 2 ; N=7) given on days 1, 8, and 15 of a 28 day cycle. Responses were evaluated using RECIST1.1. PK and serum immune cytokines were measured. Patients remained on therapy until toxicity or progression. Results: In the mouse model, clinical responses to PLD were increased. Innate immunity along with CD8+ T cell responses were also induced. In humans, treatment with PLD + VTX-2337 increased various cytokines and chemokines (G-CSF, MCP-1, MIP-1β, TNF-α). The PK of PLD was not affected by VTXE2337. The combination was well tolerated with no DLTs. AEs consisted of those seen with single-agent PLD (Gr 3/4 toxicities, N=6) or VTXE2337 (Gr 1/2 injection site reaction, transient fever, flu-like symptoms). There was 1 partial response (13%) and 63% had stable disease. Paclitaxel + VTX-2337 was also well tolerated. Conclusions: VTX-2337 enhances the effect of PLD in a preclinical model of ovarian cancer, and the combination is well-tolerated in patients. Clinical data and biomarkers consistent with immunostimulation, provide rationale for the on-going randomized, placebo-controlled, phase II trial comparing PLD vs PLD + VTX-2337 (GOG-3003, NCT01666444). Clinical trial information: NCT01666444.