tbuckley/cabot-search huggingface dataset:
Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy and safety results of the International GERCOR DREAM phase III trial.
Authors: Christophe Tournigand, Benoit Samson, Werner Scheithauer, Gérard Lledo, Frédéric Viret, Thierry Andre, Jean François Ramée, Nicole Tubiana-Mathieu, Jérôme Dauba, Olivier Dupuis, Yves Rinaldi, May Mabro, Nathalie Aucoin, Ahmed Khalil, Jean Latreille, Christophe Louvet, David Brusquant, Franck Bonnetain, Benoist Chibaudel, Aimery De Gramont
Journal: Journal of Clinical Oncology (2012)

LBA3500^ Background: Therapy targeting VEGF or EGFR demonstrated clinical activity in combination with chemotherapy (CT) in mCRC but monoclonal antibodies cannot be associated. The DREAM trial compares a maintenance therapy (MT) with bev +/- EGFR tyrosine kinase inhibitor erlotinib (E) after a first-line Bev-based induction therapy (IT) in pts with mCRC. Methods: Pts with previously untreated and unresectable mCRC were eligible. After a Bev-based IT with FOLFOX or XELOX or FOLFIRI, pts without disease progression were randomized to MT between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev+E (B 7.5 mg/kg q3w, E 150 mg/day continuously; arm B). Pts were treated until progression or unacceptable toxicity. The primary endpoint was PFS on MT. Results: The study enrolled 700 pts from 01/2007 to 11/2011 in 3 countries (France, Canada, Austria). 446 (63.7%) pts were randomized for MT (arm A, N=224; arm B, N=222). Among the 446 randomized pts, IT regimen was FOLFOX-Bev in 265 pts (59.4%), XELOX-Bev in 135 pts (30.3%), and FOLFIRI-Bev in 46 pts (10.3%). Baseline characteristics of randomized pts were (arm A/B): ECOG PS 0, 60% in both arms; normal LDH level 47%/49%; normal alkaline phosphatase level 48%/50%; synchronous metastasis 83%/82%. The median no of MT cycles was 6 in both arms. With a median follow-up of 31.0 months, 327 PFS events were observed. Median MT-PFS were 4.6 m in arm A vs 5.8 m in arm B (HR 0.73 [95%CI: 0.59-0.91], P=.005). Median PFS from inclusion were 9.2 m vs 10.2 m. During MT, in arm A vs arm B, grade 3-4 diarrhea (&lt;1% vs 9%) and grade 3 skin toxicity (0% vs 19%) were the main differences in toxicity. Severe adverse events from randomization related to B or E were 6 in arm A and 7 in arm B. Overall survival is not mature. Conclusions: The addition of erlotinib to bevacizumab after induction therapy significantly improves the duration of maintenance PFS, following induction with first-line chemotherapy plus bevacizumab, in patients with unresectable metastatic colorectal cancer.
Occupation and Lung Cancer Risk Among New Jersey White Males&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J B Schoenberg, A Stemhagen, T J Mason, J Patterson, J Bill, R Altman
Journal: JNCI Journal of the National Cancer Institute (1987)

The association of occupation with lung cancer risk was examined in a case-control study conducted in six areas of New Jersey. The study included 763 white males with incident histologically confirmed primary cancer of the trachea, bronchus, and lung and 900 general population white male controls selected from driver's license and death certificate files. Altogether, 27 employment categories had a smoking-adjusted odds ratio (OR) of 1.3 or greater; five of these with significantly high OR contributed to an occupational population attributable risk of 13%. Masons and tilesetters; janitors and cleaners; printing workers; and trucking service, warehousing, and storage workers had significantly high risks overall and for longer durations of employment. Shipbuilding workers had significantly high risk overall and for short duration of employment. Although the excess risk for all shipbuilding workers was primarily among those with reported exposure to asbestos, the risk was also high among welders, burners, sheet metal workers, and boilermakers with no reported asbestos exposure.
N997B: Phase II trial of CCI-779 in recurrent glioblastoma multiforme (GBM): Updated results and correlative laboratory analysis
Authors: E. Galanis, J. C. Buckner, M. J. Maurer, M. Hidalgo, J. I. Kreisberg, J. Peralba, R. B. Jenkins, D. J. Walsh
Journal: Journal of Clinical Oncology (2005)

1505 Background: CCI-779 is a small molecule inhibitor of the mammalian target of rapamycin (mTOR), and represents a rational therapeutic target in GBM. Methods: Recurrent GBM pts with ≤ 1 chemo regimen for progressive disease were eligible. CCI-779 dose was 250 mg IV q wk. Results: 52 pts were treated. Treatment was well tolerated: grade 3+ non-hematologic toxicity was observed in 49% and consisted mostly of hyperlipidemia, rash, and stomatitis, and grade 3+ hematologic toxicity was seen in 10%. Review of pre- and post-treatment MRI scans was performed in 40 pts. Of them, 16 (40%) had evidence of improvement in neuroimaging, consisting of significant decrease in T2 signal abnormality+/− decrease in T1 gad enhancement on stable or reduced steroid doses. Median progression free survival (PFS) for all pts was 68 days and PFS6 was 10%. PFS was significantly longer for responders (146 days) vs non-responders (55 days), (p=0.05). The incidence of grade 2 or higher hyperlipidemia in the first 2 treatment cycles was significantly higher among responders as compared to non-responders(75% vs 30%, p=0.01). The presence of PTEN deletion or EGFR amplification by FISH and the phosphorylation status of AKT in baseline tumor samples did not correlate with outcome. Decreased p70s6 kinase activity in peripheral blood mononuclear cells post treatment was not predictive of antitumor response. In contrast, a significant correlation between the presence of phosphorylated p70s6 kinase, a downstream indicator of mTOR pathway activation, in baseline tumor samples by immunohistochemistry and the likelihood of response was observed (p=0.03). Conclusions: CCI-779 is well tolerated in recurrent GBM pts. Radiographic response in CCI-779 treated pts is associated with significantly longer PFS. Development of grade 2+ hyperlipidemia on treatment appears to be a surrogate marker of radiographic improvement. High levels of phosphorylated p70s6 kinase, determined by IHC in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These preliminary observations are hypothesis generating and should be confirmed in other ongoing and future studies of mTOR inhibitors. No significant financial relationships to disclose.
Identification of biologically active cancer cells in blood and bone marrow of cancer patients
Authors: C. Panabières, J. Vendrell, O. Pellé, X. Rebillard, S. Riethdorf, V. Müller, M. Fabbro, K. Pantel
Journal: Journal of Clinical Oncology (2007)

1001 Background: Metastasis is the main cause of cancer-related death. Single disseminated tumor cells (DTC) can be detected by sensitive immunocytochemical and molecular technologies, but it is still unclear whether these cells are viable and biologically active. Methods: We applied a novel enzyme-linked immunospot assay (‘EPISPOT‘) that reveals a fingerprint of specific proteins secreted from single viable epithelial tumor cells. The membrane of ELISPOT plates were coated with monoclonal antibodies against the tumor-associated marker proteins mucin-1 (MUC1) for breast cancer and prostate-specific antigen (PSA) for prostate cancer. In addition, dual fluorescent EPISPOT assays were developed to characterize MUC1+ and PSA+ cells (i.e. CK19, FGF2 secretion). Results: Even in the absence of overt metastases (stage M0), the EPISPOT assay revealed viable tumor cells in the peripheral blood of 65% of prostate cancer patients (n=31) and the bone marrow of 54% of breast cancer patients (n=37). Respective samples from non-carcinoma controls were EPISPOT- negative, whereas 80 to 100% of samples from metastatic patients (stage M1, n=40) were positive. The number of EPISPOT-positive cells in M0-patients ranged from 2 to 197 in the blood of prostate cancer patients and 1 to 262 in the bone marrow of breast cancer patients, while M1- patients showed significantly higher counts (prostate cancer, 1–684; breast cancer, 4–813). Interestingly, subsets of MUC1- or PSA-secreting cells expressed a breast stem cell-like phenotype (MUC1 - /CK19 + ) or secreted FGF-2 as factor relevant for the growth of DTC, respectively. Conclusions: A significant fraction of cancer patients harbor viable and biologically active tumor cells in their blood and bone marrow, even in the absence of overt metastases. The multiparameter EPISPOT assay helps to identify these putative metastatic precursor cells. No significant financial relationships to disclose.
Abstract 19051: Accuracy and Internal Consistency of Cardiac Magnetic Resonance Imaging in Measuring Branch Pulmonary Arterial Flows in Conotruncal Anomalies Patients with Branch Pulmonary Arterial Stents
Authors: Matthew A Harris, Mark A Fogel, Matthew J Gillespie, Gregory L Fu, Daniel W Kim, Yoav A Dori, Marc S Keller, Kevin K Whitehead
Journal: Circulation (2012)

Introduction Conotruncal Anomalies patients may require branch pulmonary arterial (BPA) stent implantation. These ferromagnetic stents generate localized artifact that may affect phase contrast magnetic resonance (PCMR) imaging. There is little data on PCMR measurements in the presence of a BPA stent. Hypothesis PCMR acquired measurements away from the BPA stent artifact are accurate and internally consistent. Methods We retrospectively reviewed 43 consecutive repaired Conotruncal Anomalies PCMR and cine MR studies between 2005 and 2012. All patients underwent either left (30) pulmonary artery (LPA) or right (20) pulmonary artery (RPA) stent placement. Three different methods of measuring flow through the stented artery were compared: 1) main pulmonary artery (MPA) - unstented artery, 2) direct PCMR of the stented artery away from the artifact, and 3) pulmonary venous (PV) flows (see Figure). Where available, pulmonary radionuclide scintigraphy (PRS) was compared to each method. Significance was P &lt; 0.05. Results For the entire study population, the mean age and body surface area were 12.0 ± 7.0 yrs (range 1.5 - 33.2 yrs) and 1.2 ± 0.5 m2. There was good agreement without significant difference between the mean PRS and MPA derived stented artery flow (method 1) (37 ± 17 and 35 ± 21 %, r=0.731, ICC=0.8403, p=0.627) There was even better agreement between PRS and direct measurement (method 2) (39 ± 20 and 40 ± 22%, r=0.888, ICC = 0.943, p=0.757). The greatest agreement was found between method 2 and PV flows (method 3) (48 ± 17 and 47 ± 14%, , r=0.939, ICC=0.961, p=0.837). As another check for internal consistency, there was excellent correlation between the PCMR and cine MR right ventricular stroke volume 70.2 ± 40.4 and 74.0 ± 41.4 cc, r=0.983, ICC=0.989. Conclusion In the presence of a ferromagnetic BPA stent, accurate measurement of the net fractional flow ratio is feasible. PCMR adjacent to the stent artifact or pulmonary venous flows provide the most internally consistent data.
Variability of sputum inflammatory mediators in alpha-1-antitrypsin deficiency and usual COPD
Authors: Helen Stone, Gillian McNab, Robert Stockley, Elizabeth Sapey
Journal: European Respiratory Journal (2011)

Introduction: There is inherent variability in the concentrations of inflammatory mediators in stable state sputum of usual COPD patients. Patients with alpha-1-antitrypsin deficiency (ATD) have a similar spectrum of lung disease and more inflammation but variability has not been assessed. Evidence for the efficacy of treatment in A1AT is lacking; proof of concept (POC) studies indicate that augmentation increases AAT levels and reduces local mediator release. Our aims were to assess the daily variability of mediators in sputum in ATD, compared to usual COPD and to study the effects of sequential sampling to determine sample size for POC studies.

Methods: Interleukin 8 (IL8), myeloperoxidase (MPO) and leukotriene B4 (LTB4) were measured in the stable state spontaneous sputum of 12 patients with ATD and 12 usual COPD patients on 9 days over 1 month. The intra-patient variability was calculated (CV), compared between the groups, and the effects of combining results from multiple days for each patient were assessed.

Results: There was significant daily variability in all mediators, which was greater in usual COPD, despite IL8 and LTB4 concentrations being higher (p<0.01) in ATD (medians 11.29 vs 3.72 nM; and 12.16 vs 6.10 nM respectively). 3 or 5-day rolling means reduced the median CV in both groups compared to a single days' data (p<0.01) and reduced the number needed to show a 50% reduction in mediator as part of a POC study.

Conclusion: There is greater variability in usual COPD than ATD; though mediator levels were higher in ATD. Sequential sampling reduced intra-patient variability in both groups. Averaging 3 consecutive samples per patient was optimal.
Prospective study of a proactive palliative care rounding intervention in a medical ICU
Authors: Nicholas Braus, Toby C. Campbell, Kristine L. Kwekkeboom, Susan Ferguson, Carrie Harvey, Anna E. Krupp, Tara Lohmeier, Michael D. Repplinger, Ryan P. Westergaard, Elizabeth A. Jacobs, Kate Ford Roberts, William J. Ehlenbach
Journal: Intensive Care Medicine (2015)
Abstract 11502: Modifying the Seattle Heart Failure Model Improves Survival Prediction in Heart Failure Patients
Authors: Philip Jong, Sylvie A Ahn, Shrikant I Bangdiwala, Michel F Rousseau
Journal: Circulation (2012)

Background: The Seattle Heart Failure Model (SHFM) had been found to underestimate survival when validated in non-trial populations. We propose a modification of the SHFM to improve prediction of s...
Influence of Cell Proliferation on Initiating Activity of Pure Polychlorinated Biphenyls and Complex Mixtures in Resistant Hepatocyte In Vivo Assays for Carcinogenicity&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M A Hayes, S H Safe, D Armstrong, R G Cameron
Journal: JNCI Journal of the National Cancer Institute (1985)

The abilities of various pure polychlorinated biphenyls (PCB) and complex mixtures to generate resistant γ-glutamyltransferase (GGT)-positive hepatocellular nodules was evaluated in F344 rats in which hepatocytes were proliferating. The PCB examined were 2,2′,4,4′,5,5′-hexachlorobiphenyl (CAS: 35065-27-1 ), 2,2′,4,4′-tetrachlorobiphenyl, 2,2′,5,5′-tetrachlorobiphenyl, Aroclor 1254 (CAS: 11097-69-1), and a prepared mixture of pure PCB isomers and congeners similar to those found in human breast milk. The PCB were administered either to male and female suckling rats (weekly for 3 wk) during liver growth or to adult male rats (150–160 g body wt) previously subjected to two-thirds partial hepatectomy (PH). Rats were subsequently given a selection regimen consisting of 3 daily doses (20 mg/kg) of 2-acetylamino-ftuorene (2-FAA; CAS: 53-96-3) followed by either PH or necrotizing carbon tetrachloride (CAS: 56-23-5) in adult rats that previously underwent PH. None of the PCB exposures generated GGT-positive nodules after selection, whereas known initiators such as diethylnitrosamine (CAS: 55-18-5), 3-methylcholanthrene (CAS: 56-49-5), benzo[a]pyrene (CAS: 50-32-8), and 2-FAA were active initiators of nodules in suckling or hepatectomized rats. These findings indicate that short-term exposures to these PCB during liver cell proliferation do not show initiating action in an in vivo assay that detects both hepatic and nonhepatic initiating carcinogens.
Phase II treatment of medulloblastoma and pineoblastoma with melphalan: clinical therapy based on experimental models of human medulloblastoma.
Authors: H S Friedman, S C Schold, M S Mahaley, O M Colvin, W J Oakes, N A Vick, P C Burger, S H Bigner, M Borowitz, E C Halperin
Journal: Journal of Clinical Oncology (1989)

We conducted a phase II study of intravenous (IV) melphalan in the treatment of children with recurrent medulloblastoma and in the initial treatment of children with poor-prognosis medulloblastoma and pineoblastoma. There was one complete response (CR) and two partial responses (PRs) among the 12 children with recurrent medulloblastoma. There were three PRs in the four patients initially treated with melphalan for poor-prognosis medulloblastoma or pineoblastoma. Toxicity was limited to severe myelosuppression with marked neutropenia and thrombocytopenia. These results support our laboratory studies demonstrating melphalan activity in human medulloblastoma, suggest that similar activity may be demonstrated against pineoblastoma, and support further trials with this agent (administered prior to radiotherapy) in the treatment of patients with newly diagnosed poor-prognosis medulloblastoma.
Comparison of intermittent versus continuous infusion metoclopramide in control of acute nausea induced by cisplatin chemotherapy.
Authors: R M Navari
Journal: Journal of Clinical Oncology (1989)

Sixty previously untreated patients with newly diagnosed advanced-stage lung cancer (21 small-cell, 39 non-small-cell) received chemotherapy with cisplatin and etoposide. Bleomycin was also used in the patients with non-small-cell lung cancer. During the first cycle of chemotherapy, 30 patients received antiemetic therapy with intermittent metoclopramide (regimen A), and the other 30 patients received continuous infusion metoclopramide (regimen B). During the second course of chemotherapy, patients were switched to the alternate regimen. Regimen A consisted of lorazepam, 1 mg, orally; dexamethasone, 10 mg, intravenously (IV) every four hours for three doses; diphenhydramine, 0.5 mg/kg, IV every four hours for three doses; metoclopramide, 1 mg/kg, IV bolus every two hours for six doses. Regimen B was identical to A except metoclopramide was administered as 1 mg/kg, IV bolus followed by 0.5 mg/kg/h for ten hours. Fifty-eight patients completed both antiemetic regimens. Thirty-nine of the 58 patients had total control of acute nausea and vomiting (0-1 episodes) with regimen A or B. Fourteen patients had poor control of acute nausea and vomiting (more than one episode) with regimen A but total control with regimen B. Five patients had poor control with either regimen. Dystonic reactions, akathisia, or diarrhea occurred in 20 of the 58 patients on regimen A, but in only eight of the 58 patients on regimen B. Compared with intermittent bolus, continuous infusion metoclopramide is more effective in total control of acute nausea and vomiting and has less toxicity.
Belief about cure of disease after dots
Authors: P.R. Sreelatha, Sairu Philip
Journal: European Respiratory Journal (2014)

Background 

DOTS being implemented (intermittent therapy) all overIndiasince 1994. It is noticed that many smear negative cases are being started with Cat II. As in many of the previous study majority of this group are non-TB symptomatic respiratory sequele of TB. One of the reasons for starting TB drug for them is frequent complaint of patient and their belief that TB is still active in them. Here we are trying to assess belief of the patient about cure of TB after receiving DOTS.

Aim of the Study

To assess belief of the treated TB patient about cure of TB in them after receiving DOTS.

Material & Method

All tuberculosis cases registered 2003 2nd and 3rd quarter entire Alappuzha District are included in the study. They are called for a review in connection with World TB Day observance in 2005. Trained doctors as per a questionnaire interviewed them. Results were analyzed descriptively.

Observation

Of the 322 patients reported for the study, 210 were male and 112 were female. 253 were Pulmonary and 69 were extra pulmonary. 213 received Cat. I, 19 with Cat. II, 90 with Cat. III. 305 patient (94.7%) believed that they are cured of TB, 17 believes that TB disease is still active in them. There was no positive case among them.

Conclusion

There are a significant no. of patient believed that TB activity can be persist for years even after completing treatment after DOTS. Patient education is very important in this regard. So IEC campaign should address this problem also.
Long-Term Success of Irrigated Radiofrequency Catheter Ablation of Sustained Ventricular Tachycardia
Authors: Francis E. Marchlinski, Charles I. Haffajee, John F. Beshai, Timm-Michael L. Dickfeld, Mario D. Gonzalez, Henry H. Hsia, Claudio D. Schuger, Karen J. Beckman, Frank M. Bogun, Scott J. Pollak, Anil K. Bhandari
Journal: Journal of the American College of Cardiology (2016)
Occurrence of hypersensitivity to beryllium among patients with diagnosed sarcoidosis. Initial results
Authors: Lukasz Kasper, Krzysztof Sladek, Jerzy Soja, Hanna Plutecka, Marek Sanak
Journal: European Respiratory Journal (2012)

Introduction:  Sarcoidosis is a form of interstitial lung disease of unknown cause. In this disease the formations of granulomas are diagnosed also among individuals with berylliosis – an occupational disease clinically similar to sarcoidosis, but associated with hypersensitivity to beryllium.  Aim of study:  Our objective is to determine the frequency of hypersensitivity to beryllium in individuals with diagnosed sarcoidosis of lungs and to attempt to work out diagnostic methods of berylliosis.   Methodology:  Individuals selected for the research were diagnosed with sarcoidosis. All individuals were screened using a modified beryllium lymphocyte proliferation test (BeLPT). The method involved isolating blood lymphocytes, staining them with fluorescent marker (CFSE) and exposing them to beryllium sulfate (of various concentration) or mitogen (positive control). The number of dividing cells (CFSE dilution) was marked after 5 days of incubation with flow cytometry. Individuals suspected of positive proliferation test result and those suspected of the risk for beryllium compounds exposure will be examined by patch tests with beryllium sulfate.   Results:  30 individuals with sarcoidosis have been tested. 5 of them (14.3%) exhibited increased lymphocyte proliferation index.  Conclusions:  The study attempts to present a new diagnostic method of identifying hypersensitivity to beryllium. Presently, neither reliable in vitro tests for berylliosis have been standardised nor routinely carried out. Our method requires validation among patients with berylliosis, testing the method in control group and comparison of BeLPT-CFSE methods with a standard thymidine test.