tbuckley/cabot-search huggingface dataset:
Methadone rotation and initiation in outpatient cancer pain
Authors: G. L. Moura, S. Padilha, K. Vianna, M. Giublin
Journal: Journal of Clinical Oncology (2009)

e20734 Background: Methadone is an effective mu opioid agonist. Delta receptor affinity, monoamine reuptake inhibition an antagonism in N-methyl-D-aspartate receptor have been described. Because of itst long half-life and lack of standart conversion ratio outpatient use is chalinging. Methods: Retrospective review of consecutive medical reports were performed from 2002 to 2007. Patients with methadone as exclusive drug for the first two months were selected. A total of 143 patients were analyzed. Symptoms, toxicities, clinical caraceristics rotation e neuropatic pain were acessed. Results: 89 (62.2%) were female, 54 (37.7%) were male, all patients had solid tumors and were under palliative care only. 52 (36.6%) had neuropathic pain. Median age was 67 years. Median pain score at baseline was 7. After four follow-up with intervals of four days in average, 78% patients had score zero. At the end of two months we found a median (range) of 18 follow-ups performed. 127 (88.8%) patients had score zero. The remaining patients were rotated to other opioid. Neuropathic pain was improved in 36 (73%) of patients only with methadone. 16 (17%) had to use adjuvant drugs. Mean methadone dose was 10mg/day at baseline and 20mg/day at the end of two months.Sedation, obstipation and neurologic symptoms were mild and no major complication was observed. Conclusions: Methadone as initial opioid opyion showed excelent and safe response rates. Its capacity of blocking NMDA receptors may explain the high rate control for neuropathic pain. This finding was not observed in others studies. The low cost, lack of active metabolites, good tolerance in older patents and the finding in neuropathic pain should be better explored in well prospective randomized future clinical trials. No significant financial relationships to disclose.
Abstract 9654: Dipeptidyl Peptidase-4 Inhibitors May Reduce the Risk of Major Adverse Cardiovascular Events and All-cause Mortality In Patients With Type 2 Diabetes: Meta-analyses Oof Randomized Controlled Trials
Authors: Xin Sun, Afeez A Hazzan, Malgorzata Bala, Jason W Busse, Bradley C Johnston, Alonso Carrasco-Labra, Milosz Jankowski, Ignacio Neumann, Ignacio Ferreira-González, Merce Fernandez-Balsells, Lorena Rios, Dirk Bassler, Matthias Briel, Luciane Lopes, Alain Nordmann, Kari A Tikkinen, Nofisat Ismaila, Qi Zhou, Jayanti Mukherjee, Robert Frederich, Nayyar Iqbal, Stephen Walter, Gordon Guyatt
Journal: Circulation (2012)

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists, both of which have an incretin effect, represent novel, effective therapeutic approaches to treating hyperglycemia in type 2 diabetes mellitus (T2DM). Their impact on cardiovascular (CV) outcomes, however, is still under investigation. Hypotheses: We assessed the impact of DPP-4 inhibitors and GLP-1 agonists on the risk of a composite of cardiovascular death, myocardial infarction, and stroke (MACE), and on all-cause mortality (ACM) in T2DM. Methods: We searched Medline, EMBASE, and Cochrane Library for randomized controlled trials (RCTs) published up to February 2010 that compared an incretin agent versus usual care, placebo, or other active agents for patients with T2DM, and reported a pre-specified CV outcome. We also searched a major trial registry, FDA and EMEA databases, and contacted authors about unclear CV outcome information. We undertook Der-Simonian and Laird random effect meta-analyses of MACE and all-cause mortality, using inverse-variance weights and continuity correction of 0.005. We excluded total-zero-event trials. We conducted subgroup analyses using a small number of pre-specified hypotheses, including study duration, type of control, treatment mode, and risk of bias. Results: Of 61 eligible trials, data on MACE was available in 33 trials of DPP-4 inhibitors (107 events /24341 patients), and 9 of GLP-1 agonists (12/3745), and ACM in 20 trials of DPP-4 inhibitors (45/17317), and 3 of GLP-1 (3/1404). There was a significant reduction in MACE (RR 0.53, 95% CI 0.33 to 0.85) between DPP-4 inhibitors and control, and a non-significant reduction in ACM (RR 0.46, 95% CI 0.19 to 1.07). No significant differences were found between GLP-1 agonists and control in MACE (RR 0.77, 95% CI 0.13 to 4.61) or ACM (RR 3.53,0 to &gt;999). There was no significant heterogeneity detected in all analyses (p&gt;0.1). Subgroup analyses did not show any significant differences in treatment effect, except that the effect on all-cause mortality differs by treatment mode (monotherapy vs. combination/add-on therapy, interaction p=0.04). Conclusion: DPP-4 inhibitors may reduce the risk of MACE and ACM. The effect of GLP-1 agonists on CV outcomes remains uncertain.
Combination viroimmunotherapy with checkpoint inhibition to treat glioma, based on location-specific tumor profiling
Authors: Julia V. Cockle, Karishma Rajani, Shane Zaidi, Timothy Kottke, Jill Thompson, Rosa Maria Diaz, Kevin Shim, Tim Peterson, Ian F. Parney, Susan Short, Peter Selby, Elizabeth Ilett, Alan Melcher, Richard Vile
Journal: Neuro-Oncology (2015)

Systemic delivery of a complementary cDNA library expressed from the vesicular stomatitis virus (VSV) treats tumors by vaccinating against a wide range of tumor associated antigens (TAAs). For subcutaneous B16 melanomas, therapy was achieved using a specific combination of self-TAAs (neuroblastoma-Ras, cytochrome c, and tyrosinase-related protein 1) expressed from VSV. However, for intracranial B16 tumors, a different combination was therapeutic (consisting of VSV-expressed hypoxia-inducible factor [HIF]-2α, Sox-10, c-Myc, and tyrosinase-related protein 1). Therefore, we tested the hypothesis that tumors of different histological types growing in the brain share a common immunogenic signature which can be exploited for immunotherapy.Syngeneic tumors, including GL261 gliomas, in the brains of immune competent mice were analyzed for their antigenic profiles or were treated with systemic viroimmunotherapy.Several different histological types of tumors growing intracranially, as well as freshly resected human brain tumor explants, expressed a HIF-2α(Hi) phenotype imposed by brain-derived CD11b+ cells. This location-specific antigen expression was exploited therapeutically against intracranial GL261 gliomas using systemically delivered VSV expressing HIF-2α, Sox-10, and c-Myc. Viroimmunotherapy was enhanced by immune checkpoint inhibitors, associated with the de-repression of antitumor T-helper cell type 1 (Th1) interferon-γ and Th17 T cell responses.Since different tumor types growing in the same location in the brain share a location-specific phenotype, we suggest that antigen-specific immunotherapies should be based upon expression of both histological type-specific tumor antigens and location-specific antigens. Our findings support clinical application of VSV-TAA therapy with checkpoint inhibition for aggressive brain tumors and highlight the importance of the intracranial microenvironment in sculpting a location-specific profile of tumor antigen expression.
Late-breaking abstract: The applicability of urinary leukotriene E4 (uLTE4) measurement as a non-invasive method for diagnosis of aspirin exacerbated respiratory disease (AERD)
Authors: Tomasz Stachura, Joanna Kuschill-Dziurda, Marek Kaszuba, Hanna Plutecka, Marek Sanak, Krystyna Szafraniec, Lucyna Mastalerz, Krzysztof Sladek, Ewa Nizankowska-Mogilnicka, Grazyna Bochenek
Journal: European Respiratory Journal (2014)

Overproduction of cysteinyl leukotrienes (CysLT) is associated with AERD. uLTE4 is considered to be the most reliable analytic parameter of endogenous synthesis of CysLT. Aspirin challenge is a gold standard in diagnosing AERD.  Objectives - to compare baseline uLTE4 concentrations between 3 large groups of patients (AERD, aspirin tolerant asthma (ATA), healthy controls (HC)) in order to set the potential cut-off uLTE4 level for diagnosing AERD.  Patients with clinically stable AERD (n=247), ATA (n=239), HC (n=96) were enrolled. Special questionnaire was used to collect clinical data from each group. uLTE4 in morning samples was quantified by ELISA (Cayman Chemicals Co.).  Chronic sinusitis, nasal polyposis, polypectomies, and overall number of hospitalizations due to asthma were more frequent in patients with AERD. AERD patients exhibited significantly higher mean levels of uLTE4 than ATA patients and HC (2190, 616, 580 pg/mg creat. respectively); AERD vs. ATA, p 780 pg/mg creat.). The OR for diagnosing AERD vs. ATA in the 4th quartile was 5.3 (95%CI; 3.32-8.49). The ROC curve analysis identified the threshold for AERD vs. ATA at the level of uLTE4>800 pg/mg creat. (sens. 49%, spec. 81%, AUC = 0.699).  Our data suggests that uLTE4 threshold of ca. 800 pg/mg creat. is associated with an increased likelihood of diagnosing AERD. Measurement of uLTE4 could be helpful in identifying patients with AERD, who cannot undergo aspirin challenge.
Prognostic groups for management of localized Hodgkin's disease.
Authors: S B Sutcliffe, M K Gospodarowicz, D E Bergsagel, R S Bush, R E Alison, H A Bean, T C Brown, T Chua, R M Clark, J E Curtis
Journal: Journal of Clinical Oncology (1985)

Two hundred fifty-two patients receiving radical irradiation for clinical stages I and II Hodgkin's disease between 1968 to 1977 had an actuarial ten-year survival rate of 78% and a relapse-free rate of 61%. Sixty-seven patients receiving chemotherapy followed by radiation had a 78% survival rate and a 63% relapse-free rate. Independent prognostic factors for survival and relapse were age, stage, and histology. Disease bulk was predictive only of relapse. Neither site of presentation above or below the diaphragm nor presence of mediastinal involvement was predictive for survival or relapse; however, patients with large mediastinal masses (greater than or equal to 10 cm absolute diameter) had a significantly higher intrathoracic failure rate with conventional mantle irradiation. Analysis of failure, according to age, clinical stage, and histologic type, showed three groups of patients defined according to the risk of relapse with radiation therapy: those with isolated upper cervical stage IA disease (group 1, relapse rate 8%), younger patients with localized stages I and II disease of favorable histologic type (group 2, relapse rate 35%), and older patients with extensive or symptomatic stages I and II disease of less favorable histologic type (group 3, relapse rate 70%). Subsequent analysis of radiation treatment volume indicates that the use of upper abdominal irradiation for patients in group No. 2 could yield results equivalent to those achieved with radiation therapy for surgically staged patients.
Stabbed in the back: catalysts for a paradigm shift in back pain care
Authors: Jørgen Jevne
Journal: British Journal of Sports Medicine (2015)

Low back pain (LBP) is an enormous socioeconomic and emotional burden. In spite of vast efforts, the number of LBP sufferers are rising and back pain endures as a clinical conundrum. While LBP is generally recognised as a complex condition, its care is becoming progressively discordant with clinical guidelines. We are increasingly prescribing MRI, strong pain medication, injection therapy and surgery, all with highly conflicting evidence of efficacy.1

For decades we have scanned, screened and tested. We have rubbed muscles and cracked joints. Spines have been cut, carved and fixated. However, on our seemingly never-ending quest to find the pathoanatomical ‘Holy Grail’ of pain, we seem to be forgetting something:Our patients are not cars. And we are not mechanics.2 ,3

To move the field of LBP care forward, there is need for reconceptualisation. We cannot reasonably expect centuries of evolution to be marginalised into joints, muscles or …
A new HIF‐1α/RANTES‐driven pathway to hepatocellular carcinoma mediated by germline haploinsufficiency of SART1/HAF in mice
Authors: Mei Yee Koh, Mihai Gagea, Timothy Sargis, Robert Lemos, Geoffrey Grandjean, Adriana Charbono, Vasileos Bekiaris, John Sedy, Galina Kiriakova, Xiuping Liu, Lewis R. Roberts, Carl Ware, Garth Powis
Journal: Hepatology (2016)

The hypoxia‐inducible factor (HIF), HIF‐1, is a central regulator of the response to low oxygen or inflammatory stress and plays an essential role in survival and function of immune cells. However, the mechanisms regulating nonhypoxic induction of HIF‐1 remain unclear. Here, we assess the impact of germline heterozygosity of a novel, oxygen‐independent ubiquitin ligase for HIF‐1α: hypoxia‐associated factor (HAF; encoded by SART1 ). SART1−/− mice were embryonic lethal, whereas male SART1+/− mice spontaneously recapitulated key features of nonalcoholic steatohepatitis (NASH)‐driven hepatocellular carcinoma (HCC), including steatosis, fibrosis, and inflammatory cytokine production. Male, but not female, SART1+/− mice showed significant up‐regulation of HIF‐1α in circulating and liver‐infiltrating immune cells, but not in hepatocytes, before development of malignancy. Additionally, Kupffer cells derived from male, but not female, SART1+/− mice produced increased levels of the HIF‐1‐dependent chemokine, regulated on activation, normal T‐cell expressed and secreted (RANTES), compared to wild type. This was associated with increased liver‐neutrophilic infiltration, whereas infiltration of lymphocytes and macrophages were not significantly different. Neutralization of circulating RANTES decreased liver neutrophilic infiltration and attenuated HCC tumor initiation/growth in SART1+/− mice. Conclusion : This work establishes a new tumor‐suppressor role for HAF in immune cell function by preventing inappropriate HIF‐1 activation in male mice and identifies RANTES as a novel therapeutic target for NASH and NASH‐driven HCC. (H epatology 2016;63:1576‐1591)
Effect of zoledronic acid on clinically meaningful changes in pain associated with metastatic prostate cancer
Authors: K. P. Weinfurt, K. J. Anstrom, L. D. Castel, J. Brandman, K. A. Schulman
Journal: Journal of Clinical Oncology (2004)

4680 Background: Zoledronic acid (ZA) has been shown to significantly decrease skeletal-related events (SREs) in patients with prostate cancer by 11% relative to placebo. Trends were seen in pain improvement with ZA vs placebo, but there were no reliable treatment group differences. The objective of this study was to reexamine the pain outcomes using an alternative analytic framework that focuses on the frequency of clinically meaningful changes in pain scores. Methods: Patients were randomized to ZA 4mg (n=214) or placebo (n=208). The Brief Pain Inventory Composite Score (BPI) was used to assess pain at baseline, 3 weeks, 6 weeks, and every 6 weeks for a total of 60 weeks. We determined whether clinically meaningful pain changes from baseline (+/- 2 BPI points) were related to treatment assignment using a modified non-parametric rank test. Results: The rapid progression of the prostate cancer led to high rates of dropout as only 76 of 214 (35.5%) patients randomized to ZA and 62 of 208 (29.8%) patients randomized to PL completed their 60 week visit (p=0.21). At 10 of 11 assessment times, ZA patients reported more favorable clinically meaningful changes in pain scores (see table). Overall, a typical ZA patient had a 27% chance of having a favorable response (ZA>PL) compared with a typical PL patient who had an 19% chance of a favorable response (PL>ZA)—a difference that was statistically significant (95% CI: 1.1% - 15.5%). Conclusions: Patients receiving ZA were 8% more likely to have clinically beneficial changes in pain scores compared to patients receiving placebo. This is roughly consistent with the 11% difference between groups in the incidence of SREs as reported in the primary clinical analysis. Thus, ZA 4 mg significantly reduces the occurrence of skeletal-related events and the associated changes in pain they produce. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corporation
Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial.
Authors: F Robert, G A Omura, R Birch, S Krauss, R Oldham
Journal: Journal of Clinical Oncology (1984)

From 1978 to 1981, 537 patients with advanced non-small cell lung cancer were randomly assigned to three regimens containing cyclophosphamide and doxorubicin alone or in combination with methotrexate or cisplatin. Eligible patients had measurable disease and had no prior exposure to chemotherapy. Of the patients entered on the study, 505 were evaluable for toxicity and 488 were evaluable for response. The overall response rate (complete and partial responses) was only 9%. Response rates did not vary significantly with respect to treatment regimen, histologic subtypes, extent of disease, or performance status. There was no survival advantage for any regimen. The major toxicities were myelosuppression and nausea-vomiting. These doxorubicin-based chemotherapy regimens produced disappointing results in patients with advanced non-small cell lung cancer. A search for more active antitumor agents in lung cancer is necessary.
Abstract P305: Incidence of Coronary Artery Calcification and Its Association With Eicosapentaenoic Acids From The ERA JUMP Study
Authors: Akira Sekikawa, Hirotsugu Ueshima, David J Curb, Sunghee Lee, Chol Shin, Takashi Kadowaki, Kamal Masaki, Daniel Edmundowicz, Akira Fujiyoshi, Todd B Seto, Sayaka Kadowaki, Kim Sutton-Tyrrell, Aya Kadota, Rhoert W Evans, Tomonori Okamura, Katsuyuki Miura, Jina Choo, Aiman El-Saed, Lewis H Kuller
Journal: Circulation (2012)

Objectives: To compare incidence of coronary artery calcification (CAC) between men in Japan and the US and to examine whether marine n-3 fatty acids contribute to the difference in the incidence. Methods: The ERA JUMP Study is a population-based longitudinal study which has examined the progression of subclinical atherosclerosis in Japanese, Japanese American and white men aged 40-49 at baseline in 2002-2007. Incident cases of CAC were defined as those with CAC score=zero at baseline (n=278: 167 Japanese and 111 whites) and CAC score ≥10 at follow-up. Mean follow-up years were 6.2 for Japanese and 4.6 for whites. Stepwise robust logistic regression was used to determine baseline predictors of CAC incidence in each group. Generalized linear model was used to examine whether the difference in risk factors and marine n-3 fatty acids at baseline between Japanese and whites contributed to the difference in incidence rates. Results: Baseline characteristics show that levels of risk factors were similar between the two groups including LDL-C and BP. Exceptions were higher rates of smoking in Japanese (49 vs. 7%) and higher levels of HDL-C in Japanese (54 vs. 49 mg/dL). Levels of marine n-3 fatty acids were 100+% higher in Japanese. Incidence rate was significantly lower in Japanese than in whites (0.9 for Japanese vs. 2.9 for whites (per 100 person years) p&lt;0.01). Logistic regression analyses showed that predictors of CAC incidence were HDL-C, BMI, and triglycerides for whites and BP and eicosapentaenoic acids (EPA) for Japanese. Generalized linear model showed that incidence rate ratio was 0.606 after adjusting for age, follow-up time, BMI, BP, HDL-C, LDL-C, and smoking (p&lt;0.01), which remained significant after further adjusting for other risk factors. However, after further adjusting for EPA, the statistical significance disappeared (p=0.07). ( Table ) Conclusions: CAC incidence is significantly lower in Japanese than in white men. The data suggest that high levels of EPA contribute to the lower CAC incidence in Japanese. Table. Incidence rate ratio of coronary artery calcification between Japanese men and white men (n=278) Incidence rate ratio between two groups (95% CI) (Japanese vs. whites) p -value Model I 0.606 (0.427, 0.861) &lt;0.01 Model II 0.571 (0.392, 0.830) &lt;0.01 Model III 0.669 (0.431, 1.038) 0.07 Model I: Adjusted for age, follow-up time, BMI, BP sys, HDL-C pack-years of smoking and LDL-C Model II: Further adjusted for triglycerides, glucose, hypertension medication, lipid medication, CRP and alcohol Model III: Further adjusted for EPA (eicosapentaenoic acid)
Prevention of graft-versus-host disease in HLA-matched bone marrow transplantation for malignant diseases: a multicentric study of 62 patients using 3-pan-T monoclonal antibodies and rabbit complement.
Authors: E Racadot, P Hervé, F Beaujean, J P Vernant, M Flesch, E Plouvier, G Andreu, B Rio, N Philippe, G Souillet
Journal: Journal of Clinical Oncology (1987)

In order to evaluate the effectiveness and reproducibility of T cell depletion in human leukocyte antigen (HLA)-matched bone marrow graft to prevent graft-v-host disease (GVHD), our multicentric study (nine different centers) investigated 62 consecutive patients with poor prognosis leukemia or hematosarcoma from June 1984 to November 1985. The data were updated October 1, 1986, and the mean follow-up was 18 +/- 4.3 months. T cells were depleted with a combination of 3-pan-T cell monoclonal antibodies (CD2 "D66"; CD5 "A50"; CD7 "I21") with a single incubation of rabbit complement (C'). The average number of T cells infused was 0.66 X 10(6) +/- 0.56/kg body weight. Twenty-six patients received chemoprophylaxis for GVHD, 16 received methotrexate, and ten received cyclosporin A. Only a single case of severe (greater than grade II) GVHD was observed, yet the incidence of graft failure was 19%. Factors that might have influenced the occurrence of graft failure appear to be the lack of radiotherapy in the conditioning regimen; the conditioning regimen itself (fractionated total body irradiation [TBI], 12 Gy, v single dose is better than TBI, 10 Gy, but still not statistically significant); and the age of the patients (high-risk after 30 years of age). In contrast, neither the number of nucleated cells reinfused nor the level of T cell depletion (provided the T cells were below critical numbers) seemed to have an influence, nor did chemoprophylaxis for GVHD or splenectomy in chronic granulocytic leukemia (CGL) patients. The survival of graft failure patients was very poor (one of 11; survival at 15 months of the initial graft). Thus, our study demonstrates the reproducibility and high effectiveness in preventing GVHD by immunodepletion of T cells in a large-scale multicentric assay, in which compliance with the protocol of immunodepletion was reasonably good. This study thus provides interesting clues to overcoming graft rejection.
Synergistic anti-tumor activity through combinational intratumoral injection of an in-situ injectable drug depot
Authors: Da Yeon Kim, Doo Yeon Kwon, Jin Seon Kwon, Ji Hoon Park, Seung Hun Park, Hyun Ju Oh, Jae Ho Kim, Byoung Hyun Min, Kinam Park, Moon Suk Kim
Journal: Biomaterials (2016)