tbuckley/cabot-search huggingface dataset:
The impact of diabetes mellitus on survival in hepatocellular carcinoma.
Authors: G. C. Connolly, S. Safadjou, R. Kashyap, M. Orloff, A. A. Khorana, A. F. Hezel
Journal: Journal of Clinical Oncology (2010)

e14596 Background: Diabetes mellitus (DM) is associated with worse survival among patients with resectable hepatocellular carcinoma (HCC). There is limited data on the impact of DM among HCC patients treated with orthotopic liver transplantation or HCC patients with advanced disease. Methods: We conducted a retrospective review of 189 patients diagnosed with HCC between 1998 and 2004. The primary endpoint of this study was survival. Uni- and multivariate Cox regression analyses were conducted to assess the association of survival with multiple clinical covariates including DM. Results: Sixty-six of 189 (35%) patients had DM at time of HCC diagnosis. Baseline characteristics were similar between diabetic and nondiabetic patients including etiology of liver disease, Child-Pugh distribution, vasculature invasion/thrombosis, and baseline laboratory parameters (AFP level, creatinine, liver function, platelet count) with the exception of age at diagnosis (62 years for patients with DM vs. 59 for those without, p=0.001). Diabetic HCC patients had less advanced disease at presentation. Only 12% of diabetics presented with CLIP stage III disease compared to 19% of nondiabetics (p=0.032), and 38% of diabetics had multinodular disease compared to 61% of nondiabetics (p=0.003). However, the presence of DM was associated with a trend toward worse survival by univariate analysis for both transplanted patients (HR 1.5 p=0.22) and nontransplanted patients (HR 2.1, p=0.14). When controlling for several clinical factors DM was associated with significantly worse survival by multivariate Cox regression analysis (HR 1.5, p=0.027) (Table). Conclusions: DM is associated with decreased survival despite its association with an earlier stage at presentation. Further studies are required to elicit the mechanisms responsible for this association. Multivariate survival analysis Clinical covariate HR P value CLIP Stage I 1.0 Stage II 2.6 (1.5-4.6) 0.001 Stage III 4.5 (2.0-7.8) <0.0001 DM 1.5 (1.1-2.2) 0.03 Liver transplantation 0.2 (0.1-0.3) <0.0001 Largest tumor size 1.5 (1.0-2.1) 0.04 Age, hepatitis C status, and other treatments were not significant by MVA. No significant financial relationships to disclose.
Plasma levels of 5-hydroxyindole-3-acetic acid (5HIAA) as a pharmacodynamic marker of blood flow changes induced by the vascular targeting agent (VTA) 5,6 dimethyl xanthenone acetic acid, DMXAA
Authors: L. R. Kelland, B. C. Baguley, L. Zhao, Q. Ding, P. Kestell, M. Ravic, M. B. Jameson, M. J. McKeage
Journal: Journal of Clinical Oncology (2005)

3123 Background: VTAs now undergoing clinical trials include those that interact with tubulin (e.g. combretastatins and ZD6126) and the distinct tubulin-independent based flavonoid DMXAA (AS1404). DMXAA induces both direct apoptosis of tumor vascular endothelial cells and a secondary induction of vasoactive agents such as serotonin (from platelets aggregating to damaged vasculature) and tumor necrosis factor (TNFα). The study objective was to determine whether plasma levels of the serotonin metabolite, 5HIAA, correlated with DMXAA induced blood flow changes, first in mouse models and then in patients. Methods: 5HIAA levels from blood, were determined by HPLC. Mice, bearing syngeneic colon 38 subcutaneous tumors, were given single doses of DMXAA (up to ∼150mg/m2). Within a recently completed Phase I double-blind randomised study in refractory tumors; DART) patients received 20 minute intravenous infusions of DMXAA at 300 to 3000 mg/m2. Results: 5HIAA levels in mice measured 4hr post DMXAA showed a significant linear correlation with increased extravasation of the albumin binding Evans Blue from tumors (r=0.82; P<0.05); extravasation significantly correlated with reduced tumor blood flow (r = 0.88; P<0.01). In the same mice, no change in extravasation was seen in normal skin. In patients, peak 5HIAA plasma levels occurred at 4hr post dosing at dose levels >600mg/m2. Notably, there was a positive correlation between 5HIAA plasma levels and DMXAA dose up to 1200mg/m2 but thereafter a plateau was observed (even though plasma levels of free DMXAA increased linearly with dose up to 3000mg/m2). Conclusions: Increased plasma levels of 5HIAA may represent a sensitive biological marker of blood flow changes induced by the VTA, DMXAA. Dose-response data from Phase I trial patients receiving DMXAA show that the optimum biological dose to cause tumor blood flow/5HIAA changes is in the range of 1200mg/m2, that is, well below the maximum tolerated dose. Consequently, doses in this range are being studied in Phase II combination trials with taxanes (where marked synergy was seen in various preclinical tumor models) and platins. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisoma Antisoma
High-Level Globin Gene Expression Mediated by a Recombinant Adeno-Associated Virus Genome That Contains the 3′ γ Globin Gene Regulatory Element and Integrates as Tandem Copies in Erythroid Cells
Authors: Phillip W. Hargrove, Elio F. Vanin, Gary J. Kurtzman, Arthur W. Nienhuis
Journal: Blood (1997)
Clinical utility of the interferon-gamma for the diagnosis of active pulmonary tuberculosis
Authors: Svetlana Kasikovic Lecic, Slobodan Pavlovic, Vesna Kuruc, Miroslav Ilic, Darinka Kukavica
Journal: European Respiratory Journal (2011)

Introduction: A rapid diagnosis of TB is crucial not only for patients, but also for TB control in the community. Currently, T-cell based interferon gamma release assays (IGRA) are acknowledged as the best methods available for the screening of latent tuberculosis infection (LTBI) and also as aid for the diagnosis of active tuberculosis (TB). The performance of these diagnostic tests has not been evaluated in Serbia.

Aim: To compare the sensitivity of QuantiFERON-TB Gold In-tube test (QFT), tuberculin skin test (TST) and acid-fast staining of sputa in patients with culture confirmed active pulmonary TB (PTB).

Methods: The sensitivities were evaluated in 70 HIV negative patients with culture confirmed M. tuberculosis infection. The sputum culture result was used as a gold standard. TST results were analysed at 5, 10 and 15mm cut-offs. QFT test was interpreted following the manufacturer's criteria.

Results: Sensitivities of the TST using a 5, 10 and 15mm of cut-offs were low: 55,7%, 51,4%, 45,7% respectively. Sensitivity of QFT (68,6%) was higher than that for all the TST sensitivities. The overall agreement between TST (all cut-offs) and QFT was poor. Sensitivity of the acid-fast staining of sputa was 75,7%. Naither detected statistical significant difference between sensitivity of QFT and the acid-fast staining of sputa, nor between of QFT and TST≥5 and TST ≥10 mm, but detected between sensitivity of QFT and TST≥15 mm (p=0,01).

Conclusion: Although findings have revealed a generally low sensitivity of the QFT, our opinion is that QFT can be used as adjunct diagnostic technique for active TB disease.
DPYD single nucleotide polymorphisms (SNPs) and haplotypes in patients (pts) with metastatic colorectal cancer and toxicity of capecitabine.
Authors: M. J. Deenen, J. Tol, A. M. Burylo, A. De Boer, A. Vincent, H. Guchelaar, J. H. Beijnen, C. J. Punt, J. H. Schellens, A. Cats
Journal: Journal of Clinical Oncology (2010)

3099 Background: Capecitabine is the oral prodrug of 5-FU, which is inactivated for 85% by dihydropyrimidine dehydrogenase (DPD, DPYD). The aim of this study was to determine the effect of DPYD SNPs and haplotypes on toxicity and efficacy of capecitabine. Methods: Toxicity and survival were determined in 568 previously untreated pts with metastatic colorectal cancer participating in the CAIRO2 trial and randomly assigned to capecitabine, oxaliplatin, bevacizumab ± cetuximab (Tol et al, NEJM 2009). The entire DPYD coding region was sequenced in 50 pts that presented with grade ≥3 capecitabine-related toxicity within the first 2 treatment cycles. SNP frequencies were compared to those in 100 pts randomly drawn from the entire population. SNPs that appeared of clinical relevance from this nested case-cohort part were analyzed in all 568 pts. DPYD SNPs and haplotypes were correlated with toxicity, dose modifications of capecita-bine, and survival. Results: 29 SNPs were detected in the case-cohort population, 8 of which were analyzed in all 568 pts. IVS14+1G>A, 2846A>T, 1236>A, 2194G>A and 496A>G were associated with diarrhea grade 3-4 with positive predictive values of 0.71, 0.63, 0.50, 0.41 and 0.33, respectively (p<0.05). All 7 pts polymorphic for IVS14+1G>A developed any grade 3-4 toxicity with one chemotherapy-induced death. Due to toxicity, mean dose reductions of capecitabine of 50% and 25% were applied in IVS14+1G>A or 2846A>T variant allele carriers, respectively (p<0.005). SNPs were not associated with survival. Pts were categorized in 6 haplotype groups (HP1-6). HP3 (heterozygous for 85T>C and wild type for other SNPs) pts had a decreased risk for diarrhea grade 3-4 (p=0.002). Pts with 2 variant haplotype alleles and pts heterozygous for rare (<3%) haplotypes (HP5) showed increased risks for diarrhea grade 3-4 (p=0.01). HP5 was associated with increased overall survival (p=0.03). Conclusions: DPYD IVS14+1G>A and 2846A>T are predictive markers for severe toxicity requiring strong dose reductions. DPYD haplotypes could assist in selecting pts at risk for toxicity to capecitabine. The predictive value of DPYD SNPs and haplotypes for survival appears to be limited. No significant financial relationships to disclose.
Feline Leukemia Virus Envelope Glycoprotein Vaccine: Preparation and Evaluation of Immunizing Potency in Guinea Pig and Cat&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ronald A. Salerno, E. Dale Lehman, Vivian M. Larson, Maurice R. Hilleman
 4
Journal: JNCI Journal of the National Cancer Institute (1978)

Envelope glycoprotein of feline leukemia virus (FeLV), strain FeLV-1, was extracted with 2% Triton X-100 and 0.43 M NaCI In 10 mM Tris (pH 7.5) and purified by ion-exchange chromatography on phosphocellulose. Purified FeLV envelope gp75 had a molecular weight of 75,000 daltons and induced antibodies of high titers in the goat. These antibodies specifically neutralized FeLV, precipitated radiolabeled FeLV envelope gp75, and lysed FL74 cells. The immunogenicity of purified FeLV envelope gp75 with and without adjuvant was tested and compared in guinea pigs and cats. Administration of 20 μg of FeLV envelope gp75 to guinea pigs in either alum or adjuvant 65 formulation induced neutralizing antibody [geometric mean titer (GMT), 8-25], radioimmune precipitating antibody (GMT, 1,382-6,450), and cytotoxic antibody (titer, ≥2) in all animals. Aqueous FeLV envelope gp75 vaccine induced neutralizing antibody (GMT, <4) in only 50% of the guinea pigs. In contrast to results with guinea pigs, immunization of speclflc-pathogen-free cats, 10-15 weeks old, with twice the guinea pig dose level of FeLV envelope gp75 (40 μg) induced significantly less immune response to FeLV when its envelope gp75 was administered in alum or Freund's adjuvant and little or no response when FeLV envelope gp75 was given as aqueous or adjuvant 65 formulation. Cats immunized with 40 μg FeLV envelope gp75 in alum or Freund's adjuvant developed radiolmmune antibody with GMT's of 127-207 [100% seroconverslon (SC)], but little or no neutralizing antibody (22-38% SC; GMT, <2) or cytotoxic antibody (0-44% SC) developed.
Tablet computer-based multimedia enhanced medical training improves performance in gastroenterology and endoscopy board style exam compared with traditional medical education
Authors: Daniel C Baumgart, Ilja Wende, Ulrike Grittner
Journal: Gut (2015)

We read with interest the paper by Ekkelenkamp et al ,1 who found that the early use of validated simulators during endoscopy training expedites the learning of procedural skills.

Indeed, traditional teaching concepts do not take full advantage of advanced technology. We therefore prospectively investigated the impact of our self-developed custom wireless-enabled tablet PC-based multimedia training and test system on gastrointestinal endoscopy self-assessment program (GESAP®) exam performance. Control and the tablet groups were tested at the beginning and the end of their rotation by administration of all 200 random generator selected, equally distributed questions from all 11 categories (biliary, colorectal, oesophagus, intestines, nutrition, pancreas, patient preparation, paediatrics, surgery) parsed from the current GESAP® pool.

Medical students and residents doing an inpatient service rotation were alternatingly assigned to either the active test (tablet PC) or traditional education (control) group, respectively. The multimedia training package included access to the institutional collaborative online course management systems (Moodle and Blackboard), eBooks, eJournals, educational slide kits, podcasts, videos, animations, images from major biomedical and scientific publishers or professional societies, as well as twitter …
Development of core outcome sets in hidradenitis suppurativa: systematic review of outcome measure instruments to inform the process
Authors: J.R. Ingram, S. Hadjieconomou, V. Piguet
Journal: British Journal of Dermatology (2016)

The recent hidradenitis suppurativa (HS) Cochrane review identified outcome measure heterogeneity as an important issue to address when designing future HS trials. Our objective was to follow the Harmonising Outcome Measures for Eczema (HOME) roadmap, by performing a systematic review of HS outcome measure instruments to inform the development of an HS core outcome set. We performed a systematic review to identify validation evidence for outcome measure instruments used in HS randomized controlled trials (RCTs), and assessed the methodological quality of all HS outcome measure validity studies using the COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The 12 RCTs included in the Cochrane review utilized 30 outcome measure instruments, including 16 physician‐reported instruments, 11 patient‐reported instruments and three composite measures containing elements of both. Twenty‐seven (90%) of the instruments lacked any validation data. Two further instruments have been developed and partially validated. Of the seven studies meeting our inclusion criteria, six were of 'fair' or 'poor' methodological quality, in part because most of the studies were not primarily designed for instrument validation. The HiSCR instrument is supported by good‐quality validation data, but there are gaps, including assessment of internal consistency, inter‐rater reliability and minimal clinically important difference, and convergent validity fell below the acceptable range for some comparisons. Multiple, usually unvalidated, outcome measure instruments have been used in HS RCTs. Where validation evidence is available there are issues of low methodological quality or incomplete validity assessment and so, currently, no instruments can be fully recommended.
Development of a polyvalent cellular vaccine against ovarian cancer using ascites-derived antigen presenting cells
Authors: Sarah Adams, Andrea Facciabene, Xiaohui Peng, George Coukos
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4992 

Objective: To determine whether antigen presenting cells in malignant ascites (aAPC) can elicit an anti-tumor immune response after ex vivio stimulation with Toll-like receptor agonists (TLR-a) in a mouse model of ovarian cancer.    Methods: C57/b6 mice were injected with murine ovarian cancer cell lines, ID8-Vegf-β-defensin and ID8-E7. Both aAPC and T cells harvested from ascites were subjected to flow cytometric characterization using antibodies to CD3, CD4, CD8, FoxP3, CD11c, CD14, CD80, CD86,CD123, B7-H1, and MHC II.    Adherent CD45+ cells from ascites were considered candidate aAPC and stimulated with TLR-a, including LPS, CpG, and Poly I:C along with a blocking antibody to the IL-10 receptor (IL-10Rab) or to MHC-I. After 48 hours, treated aAPC were incubated with T cells harvested from autologous ascites specimens, and IFN-γ production was assessed by ELISA. Peripheral T cells from a second group of mice vaccinated with E7/E8 DNA were used as controls.    To study the therapeutic potential of these cells, healthy mice were injected subcutaneously with a cellular vaccine composed of stimulated aAPC. After two weeks, peripheral T cells from vaccinated mice were incubated with stimulated aAPC in vitro . IFN-γ production was measured by ELISA. Vaccinated mice were then injected with tumor to evaluate for survival differences after immunization.    Results: Cells from fresh ascites expressed CD80, CD86, and high levels of MHC II. After 48 hours in culture, stimulated cells expressed more CD14, CD80, CD86, B7-H1, and CD11c, but less CD123, than unstimulated cells.    Functional studies showed high levels of IFN-γ production by T cells after incubation with aAPC treated with LPS, CpG, and IL-10Rab. Autologous ascites-derived T cells consistently produced more IFN-γ than control T cells. Addition of an anti-MHC I antibody blocked this effect, suggesting that CD8 cells were primarily responsible for IFN-γ production.    Finally, peripheral T cells derived from healthy mice vaccinated with stimulated aAPC produced IFN-γ following exposure to stimulated aAPC in vitro. No IFN-γ was produced by T cells from mice vaccinated with unstimulated aAPC. Mice vaccinated with treated aAPC were less likely to develop tumor.    Conclusions: APC present in malignant ascites have engulfed tumor antigen in vivo , and can be stimulated to elicit a polyclonal anti-tumor cellular immune response in a mouse model. This immunity is transferable as a cellular vaccine and confers protection from tumor challenge. This finding has significant translational potential as a rapid protocol for immunotherapy for select patients with ovarian cancer.
Lymphosarcomas in Two Gibbons (Hylobates lar) With Associated C-Type Virus2
Authors: S. P. Snyder, D. L. Dungworth, T. G. Kawakami, E. Callaway, D. T-L. Lau
Journal: JNCI Journal of the National Cancer Institute (1973)

We examined the tissues from 2 cases of lymphosarcoma in gibbons by light and electron microscopy. The animals were part of a group of 6 gibbons purchased together and used in a study on the aging of the spinal column. The animals, a male and a female, were about 3.5 years old at death. Numerous C-type virus particles, similar in morphology and apparent mode of production to those of the avian, murine, and feline leukemia-sarcoma complex, were found in all tissues examined. The particles were approximately 100 nm in diameter, with nucleoids of about 65 nm, and were found budding from, and free between, neoplastic lymphoid cells, histiocytic cells, and megakaryocytes.
Neoadyuvant weekly docetaxel-based chemoradiotherapy (CRT) for locally advanced gastric carcinoma: A dose-escalating study
Authors: A. Viudez, J. Rodriguez, J. A. Diaz-Gonzalez, J. Aristu, J. Hernandez, L. Arbea, A. Chopitea, M. Ponz-Sarvise, F. Martinez-Regueira, J. Garcia-Foncillas
Journal: Journal of Clinical Oncology (2008)

15657 Background: To determine the toxicity profile and dose limiting toxicity (DLT) of a neoadjuvant schedule including escalating doses of docetaxel with oxaliplatin, capecitabine and concurrent radiotherapy in locally advanced gastric cancer. Methods: The schedule consisted on induction chemotherapy followed by CRT. Fixed doses of oxaliplatin (50 mg/m2; weeks 1,2,4, and 5) plus capecitabine (650 mg/m2 bid Monday to Friday) were combined with escalating doses of docetaxel, beginning at 15 mg/m2 (DL1:15 mg/m2; DL2:20 mg/m2; DL3:25mg/m2; DL4:30 mg/m2; weeks 1,2,4 and 5). Radiotherapy was delivered concurrently (45 Gy in 5 weeks). When indicated resection was attempted 5 to 6 weeks after CRT was completed. Results: Between 07/05 and 12/07, 23 patients with histological confirmed locally advanced gastric adenocarcinoma were included. Non-grade III/IV hematologic toxicities were observed during the two cycles of induction chemotherapy. No hematologic-DLT was observed at level 1 and 2. However, dose level 3 was expanded due to grade 3 neutropenia and asthenia in 1 patient. Subsequently, nine more patients were included at dose level 3, without DLTs. 2 of 2 patients at level 4 experienced DLTs (grade 3 leukopenia, asthenia, anorexia and abdominal discomfort). The main grade 3–4 toxicities included leukopenia (17,4%), mucositis( 8,3%) vomiting (13%), gastritis (4,2%), asthenia (21,7%) and anorexia (21,7%). According to Becker response criteria, major response (Ia-Ib) was achieved in 68,4% of the operated patients. An R0 resection was achieved in 90% of the patients. Conclusions: Dose level 3 (25 mg/m2) is the recommended dose for phase II trials. No significant financial relationships to disclose.
Mobile Telephone Text Messaging for Medication Adherence in Chronic Disease
Authors: Jay Thakkar, Rahul Kurup, Tracey-Lea Laba, Karla Santo, Aravinda Thiagalingam, Anthony Rodgers, Mark Woodward, Julie Redfern, Clara K. Chow
Journal: JAMA Internal Medicine (2016)

Adherence to long-term therapies in chronic disease is poor. Traditional interventions to improve adherence are complex and not widely effective. Mobile telephone text messaging may be a scalable means to support medication adherence.To conduct a meta-analysis of randomized clinical trials to assess the effect of mobile telephone text messaging on medication adherence in chronic disease.MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL (from database inception to January 15, 2015), as well as reference lists of the articles identified. The data were analyzed in March 2015.Randomized clinical trials evaluating a mobile telephone text message intervention to promote medication adherence in adults with chronic disease.Two authors independently extracted information on study characteristics, text message characteristics, and outcome measures as per the predefined protocol.Odds ratios and pooled data were calculated using random-effects models. Risk of bias and study quality were assessed as per Cochrane guidelines. Disagreement was resolved by consensus.Sixteen randomized clinical trials were included, with 5 of 16 using personalization, 8 of 16 using 2-way communication, and 8 of 16 using a daily text message frequency. The median intervention duration was 12 weeks, and self-report was the most commonly used method to assess medication adherence. In the pooled analysis of 2742 patients (median age, 39 years and 50.3% [1380 of 2742] female), text messaging significantly improved medication adherence (odds ratio, 2.11; 95% CI, 1.52-2.93; P < .001). The effect was not sensitive to study characteristics (intervention duration or type of disease) or text message characteristics (personalization, 2-way communication, or daily text message frequency). In a sensitivity analysis, our findings remained robust to change in inclusion criteria based on study quality (odds ratio, 1.67; 95% CI, 1.21-2.29; P = .002). There was moderate heterogeneity (I2 = 62%) across clinical trials. After adjustment for publication bias, the point estimate was reduced but remained positive for an intervention effect (odds ratio, 1.68; 95% CI, 1.18-2.39).Mobile phone text messaging approximately doubles the odds of medication adherence. This increase translates into adherence rates improving from 50% (assuming this baseline rate in patients with chronic disease) to 67.8%, or an absolute increase of 17.8%. While promising, these results should be interpreted with caution given the short duration of trials and reliance on self-reported medication adherence measures. Future studies need to determine the features of text message interventions that improve success, as well as appropriate patient populations, sustained effects, and influences on clinical outcomes.