tbuckley/cabot-search huggingface dataset:
Health-Related Quality of Life Measurement in Randomized Clinical Trials in Surgical Oncology
Authors: Jane M. Blazeby, Kerry Avery, Mirjam Sprangers, Hynek Pikhart, Peter Fayers, Jenny Donovan
Journal: Journal of Clinical Oncology (2006)

Purpose There is debate about the value of measuring health-related quality of life (HRQL) in clinical trials in oncology because of evidence suggesting that HRQL does not influence clinical decisions. Analysis of HRQL in surgical trials, however, may inform decision making because it provides detailed assessment of the immediate detrimental short-term impact of surgery on HRQL that needs to be considered against the long-term survival benefits and functional outcomes of surgery. This study evaluated whether HRQL in randomized trials in surgical oncology contributes to clinical decision making. Methods A systematic review identified randomized trials in surgical oncology with HRQL. Trials were evaluated independently by two reviewers and the value of HRQL in clinical decision making was categorized in three ways: whether trial investigators reported that HRQL influenced final treatment recommendations, whether trial investigators reported that HRQL would be useful for informed consent, and whether HRQL was assessed robustly according to predefined criteria. Results Thirty-three randomized trials with valid HRQL questionnaires were identified; 22 (67%) concluded that HRQL outcomes influenced treatment decisions or provided valuable data for informed consent, and seven of these trials had robust HRQL design. Another five trials had robust HRQL design but investigators reported that HRQL outcomes were not clinically important enough to influence treatment recommendations. Conclusion In surgical trials in oncology, HRQL informed clinical decision making. It is recommended that HRQL be included in relevant surgical trials, and that information be used to inform clinicians and patients about the impact of surgery on short- and long-term HRQL.
Monitored Isoniazid Prophylaxis for Low-Risk Tuberculin Reactors Older Than 35 Years of Age: A Risk-Benefit and Cost-Effectiveness Analysis
Authors: Shelley R. Salpeter
Journal: Annals of Internal Medicine (1997)

Background: Isoniazid chemoprophylaxis effectively prevents the development of active infectious tuberculosis. Current guidelines recommend withholding this prophylaxis for low-risk tuberculin reactors older than 35 years of age because of the risk for fatal isoniazid-induced hepatitis. However, recent studies have shown that monitoring for hepatotoxicity can significantly reduce the risk for isoniazid-related death. Objective: To evaluate the effectiveness and cost-effectiveness of monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age. Design: A Markov model was used to compare the health and economic outcomes of prescribing or withholding a course of prophylaxis for low-risk reactors 35, 50, or 70 years of age. Subsequent analyses evaluated costs and benefits when the effect of transmission of Mycobacterium tuberculosis to contacts was included. Measurements: Probability of survival at 1 year, number needed to treat, life expectancy, and cost per year of life gained for individual persons and total population. Results: Isoniazid prophylaxis increased the probability of survival at 1 year and for all subsequent years. For 35-year-old, 50-year-old, and 70-year-old tuberculin reactors, life expectancy increased by 4.9 days, 4.7 days, and 3.1 days, respectively, and costs per person decreased by $101, $69, and $11, respectively. When the effect of secondary transmission to contacts was included, the gains in life expectancy per person receiving prophylaxis were 10.0 days for 35-year-old reactors, 9.0 days for 50-year-old reactors, and 6.0 days for 70-year-old reactors. Costs per person for these cohorts decreased by $259, $203, and $100, respectively. The magnitude of the benefit of isoniazid prophylaxis is moderately sensitive to the effect of isoniazid on quality of life. The hypothetical provision of isoniazid prophylaxis for all low-risk reactors older than 35 years of age in the U.S. population could prevent 35 176 deaths and save $2.11 billion. Conclusions: Monitored isoniazid prophylaxis reduces mortality rates and health care costs for low-risk tuberculin reactors older than 35 years of age, although reductions for individual patients are small. For the U.S. population, however, the potential health benefits and economic savings resulting from wider use of monitored isoniazid prophylaxis are substantial. We should consider expanding current recommendations to include prophylaxis for tuberculin reactors of all ages with no contraindications.
CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy
Authors: D. Ennishi, K. Takeuchi, M. Yokoyama, H. Asai, Y. Mishima, Y. Terui, S. Takahashi, H. Komatsu, K. Ikeda, M. Yamaguchi, R. Suzuki, M. Tanimoto, K. Hatake
Journal: Annals of Oncology (2008)
Identification of a novel antigen-presenting cell population modulating antiinfluenza type 2 immunity
Authors: Jae-Kwang Yoo, Carole L. Galligan, Carl Virtanen, Eleanor N. Fish
Journal: The Journal of Experimental Medicine (2010)

Antiinfluenza type 2 (T2) immunity contributes to both immunopathology and immunoprotection, yet the underlying mechanisms modulating T2 immunity remain ill defined. We describe a novel mouse antigen (Ag)-presenting cell (APC), designated late-activator APC (LAPC). After pulmonary influenza A (H1N1) virus infection, LAPCs enter the lungs, capture viral Ag, and subsequently migrate to the draining lymph node (DLN) and spleen, with delayed kinetics relative to dendritic cells (DCs). In the DLN, influenza virus-activated LAPCs present Ag and selectively induce T helper type 2 (Th2) effector cell polarization by cell-cell contact-mediated modulation of GATA-3 expression. In adoptive transfer experiments, influenza virus-activated LAPCs augmented Th2 effector T cell responses in the DLN, increased production of circulating antiinfluenza immunoglobulin, and increased levels of T2 cytokines in bronchoalveolar lavage fluid in recipient influenza virus-infected mice. LAPC-recipient mice exhibited exacerbated pulmonary pathology, with delayed viral clearance and enhanced pulmonary eosinophilia. Collectively, our results identify and highlight the importance of LAPCs as immunomodulators of T2 immunity during influenza A virus infection.
Testing for Colon Neoplasia Susceptibility Variants at the Human COX2 Locus
Authors: G. L. Wiesner, P. Platzer, S. Buxbaum, S. Lewis, M. MacMillen, J. Olechnowicz, J. Willis, A. Chakravarti, R. C. Elston, S. D. Markowitz
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Siblings and other first-degree relatives of patients with “sporadic” (i.e., apparently nonfamilial) colorectal cancer or precursor adenomatous colon polyps have an increased risk of developing colon neoplasia. This observation suggests the presence of inherited genetic determinants for sporadic colon neoplasia. Mice homozygous for a null cyclooxygenase 2 (COX2) (also called PTGS2) allele have a dramatically reduced susceptibility to the development of intestinal adenomas. In humans, use of pharmacologic inhibitors of COX2 enzyme activity are associated with reduced risk of colon neoplasia. This study examined whether the human COX2 locus may be linked to colon neoplasia in humans. Methods: We used the affected sibling-pair method to test for linkage of the human COX2 locus to colon neoplasia. Results: We examined 74 concordantly affected sibling pairs from 46 sibships with colon neoplasia. One hundred five siblings from these sibships were diagnosed with either colorectal cancer or colon adenomatous polyps before age 65 years. No linkage between COX2 and colon neoplasia was found by use of a multipoint model-free linkage analysis (estimate of allele sharing was 0.44; standard error = ±0.04; 95% confidence interval = 0.36 to 0.52). Moreover, even allowing for heterogeneity, the potential that a COX2 colon neoplasia susceptibility variant was present within a substantial subset of these sibships was strongly excluded under either a recessive or a dominant inheritance model (95% confidence to exclude a model in which 2.7% or more of the sibling pairs harbor a dominant susceptibility allele). Conclusions: This study of concordantly affected sibling pairs thus demonstrates that variations in the COX2 gene are unlikely to be a source of individual susceptibility to colon neoplasia in humans.
Met Activation Is Required for Early Cytoprotection after Ischemic Kidney Injury
Authors: Sherene Mason, Carlos Hader, Arnaud Marlier, Gilbert Moeckel, Lloyd G. Cantley
Journal: Journal of the American Society of Nephrology (2013)

Renal proximal tubule epithelial cells express high levels of the hepatocyte growth factor receptor Met, and both the receptor and ligand are upregulated after ischemic injury. Activation of the Met receptor after hepatocyte growth factor stimulation in vitro promotes activities involved in kidney repair, including cell survival, migration, and proliferation. However, characterizing the in vivo role of these signaling events in proximal tubule responses to kidney injury has been difficult because global Met knockout results in embryonic lethality due to placental and liver abnormalities. Here, we used γGT-Cre to knockout Met receptor expression selectively in the proximal tubules of mice (γGT-Cre;Met(fl/fl)). The kidneys of these mice developed normally, but exhibited increased initial tubular injury, tubular cell apoptosis, and serum creatinine after ischemia/reperfusion compared with γGT-Cre;Met(+/+) kidneys. These changes in γGT-Cre;Met(fl/fl) mice correlated with a selective reduction in PI3K/Akt activation in response to injury and subsequent decreases in inhibitory phosphorylation of the proapoptotic factor Bad and activating phosphorylation of the ribosomal regulatory protein p70-S6 kinase. Moreover, tubular cell proliferation after ischemia/reperfusion was delayed in γGT-Cre;Met(fl/fl) mice. In conclusion, this study identifies Met-dependent phosphoinositide 3-kinase activation in proximal tubules as a critical determinant of initial tubular cell survival and reparative proliferation after ischemic injury.
Observation for Clinically Localized Prostate Cancer
Authors: Joel B. Nelson
Journal: Journal of Clinical Oncology (2014)

Article Tools ONCOLOGY GRAND ROUNDS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2013.54.2043 Journal of Clinical Oncology - published online before print March 17, 2014 PMID: 24637994 Observation for Clinically Localized Prostate Cancer Joel B. NelsonxJoel B. NelsonSearch for articles by this author Show More University of Pittsburgh School of Medicine, Pittsburgh, PA https://doi.org/10.1200/JCO.2013.54.2043 First Page Full Text PDF Figures and Tables © 2014 by American Society of Clinical Oncology
Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum
Authors: David J Pombo, Gregor Lawrence, Chakrit Hirunpetcharat, Christine Rzepczyk, Michelle Bryden, Nicole Cloonan, Karen Anderson, Yuvadee Mahakunkijcharoen, Laura B Martin, Danny Wilson, Salenna Elliott, Suzanne Elliott, Damon P Eisen, J Brice Weinberg, Allan Saul, Michael F Good
Journal: The Lancet (2002)
Update in the management of chronic lymphocytic leukemia
Authors: Kami J Maddocks, Thomas S Lin
Journal: Journal of Hematology & Oncology (2009)

Advances in the treatment of chronic lymphocytic leukemia (CLL) have improved initial overall response (OR) rates, complete response (CR) rates and progression free survival (PFS). Despite these advances, CLL remains incurable with standard therapies. Thus, there remains a need for more effective therapies in both the upfront and relapsed setting, particularly for patients with high-risk cytogenetic abnormalities such as del(11q22) and del(17p13). The 2008 American Society of Hematology (ASH) Annual Meeting featured several presentations which highlighted the ongoing clinical advances in CLL. The benefit of adding rituximab to purine analog therapy in the upfront setting was demonstrated by a large randomized study which showed that the addition of rituximab to fludarabine and cyclophosphamide (FCR) significantly improved OR, CR and PFS. The improvement in PFS directly resulted from an improved ability to eliminate minimal residual disease (MRD) in the peripheral blood, highlighting the importance of MRD eradication. However, a multi-center study suggested that the high CR rates to chemoimmunotherapy regimens such as FCR obtained in academic centers may not be reproducible when the same regimens are given in the community setting. The immunomodulatory drug lenalidomide is active in relapsed high-risk CLL, but two studies of lenalidomide in previously untreated CLL patients failed to achieve a CR and were associated with significant tumor lysis, tumor flare and hematologic toxicity. In the relapsed setting, a combination study of the bifunctional alkylator bendamustine and rituximab (BR) demonstrated a high OR rate in patients with del(11q22) and del(17p13), indicating that further studies to define's bendamustine activity are warranted in high-risk CLL. Similarly, the CDK inhibitor flavopiridol demonstrated significant clinical activity and durable remissions in heavily treated, refractory CLL patients with high-risk cytogenetic features and bulky lymphadenopathy. The monoclonal anti-CD20 antibody ofatumumab appeared to be superior to rituximab in relapsed CLL patients with bulky nodal disease or high-risk cytogenetic features. Ongoing studies of these agents and other novel therapeutic agents in clinical development hold forth the promise that treatment options for CLL patients will continue to expand and improve.
Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group.
Authors: N Asou, K Adachi, J Tamura, A Kanamaru, S Kageyama, A Hiraoka, E Omoto, H Akiyama, K Tsubaki, K Saito, K Kuriyama, H Oh, K Kitano, S Miyawaki, K Takeyama, O Yamada, K Nishikawa, M Takahashi, S Matsuda, S Ohtake, H Suzushima, N Emi, R Ohno
Journal: Journal of Clinical Oncology (1998)

PURPOSE We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.
Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome
Authors: Mitchell R. McGill, Vincent S. Staggs, Matthew R. Sharpe, William M. Lee, Hartmut Jaeschke
Journal: Hepatology (2014)

Acetaminophen (APAP) overdose is a major cause of acute liver failure (ALF). Numerous studies have shown that APAP hepatotoxicity in mice involves mitochondrial dysfunction, and recent data suggest that this is also the case in humans. We have previously shown that glutamate dehydrogenase (GDH), mitochondrial DNA (mtDNA), and nuclear DNA (nDNA) fragments can be measured in circulation of overdose patients as mechanistic biomarkers of mitochondrial damage and damage-associated molecular patterns. In the present study, our aim was to determine whether these biomarkers are higher in serum from nonsurvivors of APAP-induced ALF (AALF), compared to survivors. GDH, mtDNA, and nDNA fragments were measured in serum from AALF patients who did (n = 34) or did not (n = 35) recover. Importantly, all three were significantly increased in patients who died, compared to those who survived (GDH: 450 ± 73 vs. 930 ± 145 U/L; mtDNA: 21 ± 6 vs. 48 ± 13 and 33 ± 10 vs. 43 ± 7 ng/mL for two different genes; nDNA fragments: 148 ± 13 vs. 210 ± 13% of control). Receiver operating characteristic (ROC) curve analyses revealed that nDNA fragments, GDH, and mtDNA were predictive of outcome (area under the curve [AUC], study admission: 0.73, 0.70, and 0.71 or 0.76, respectively, P &lt; 0.05; AUC, time of peak ALT: 0.78, 0.71, and 0.71 or 0.76, respectively, P &lt; 0.05), and the results were similar to those from the Model for End-Stage Liver Disease (MELD; AUC, peak MELD: 0.77; P &lt; 0.05). Conclusions : Our data suggest that patients with more mitochondrial damage are less likely to survive, demonstrating that mitochondria are central in the mechanisms of APAP hepatotoxicity in humans. Clinically, serum nDNA fragments, GDH, and mtDNA could be useful as part of a panel of biomarkers to predict patient outcome. (Hepatology 2014;60:1336–1345)
Metabolic oxidation of pyruvate and lactate during early myocardial reperfusion.
Authors: B Renstrom, S H Nellis, A J Liedtke
Journal: Circulation Research (1990)

We have previously described the rates of oxidation for long-chain fatty acids and glucose in stunned myocardium during early reflow after moderately severe regional ischemia. The purpose of these studies was to characterize the rates of pyruvate and lactate oxidation during comparable periods of reflow. In the main protocol, pyruvate oxidation was defined at two conditions of coronary flow and at two levels of fatty acids in the coronary perfusate. Twenty animals were prepared using the extracorporeally perfused, working swine heart model. In five control (group 1) hearts, flow in the left anterior descending coronary artery was maintained at aerobic levels during a 115-minute perfusion trial. In 15 hearts (groups 2 and 3), flow was held at aerobic levels for 30 minutes, reduced acutely by 60% for 45 minutes, and restored again to aerobic levels for the final 40-minute reflow. In the five control hearts and in 10 of the reperfused hearts (group 2), 20% Intralipid (KabiVitrum, Alameda, California) with heparin was infused to raise serum fatty acids to an average of 0.95 +/- 0.08 mumol/ml, whereas in the five remaining nonsupplemented group 3 hearts, serum levels of fatty acids were 0.49 +/- 0.10 mumol/ml. Ischemia in supplemented and nonsupplemented hearts caused a decline in regional mechanical performance (-40 delta % and -39 delta % below aerobic values in active shortening) that failed to recover completely (-16 delta % and -25 delta % below aerobic values in active shortening) during reflow.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of manual and automatic CPAP titration in patients with sleep apnea/hypopnea syndrome.
Authors: P Lloberes, E Ballester, J M Montserrat, E Botifoll, A Ramirez, A Reolid, C Gistau, R Rodriguez-Roisin
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Automatic CPAP (auto-CPAP) is engineered to automatically provide a positive pressure to the upper airway in response to apnea, hypopnea, airflow limitation, or snoring in patients with the sleep apnea/ hypopnea syndrome (SAHS). Self-adjusted CPAP has theoretical advantages over traditional fixed CPAP. We investigated the value of auto-CPAP regulation in 20 patients with SAHS in order to predict future fixed-level CPAP needs, as an alternative method to conventional polysomnographically (PSG)-controlled CPAP titration. This was accomplished through comparison of the optimal CPAP level obtained with PSG with that obtained with auto-CPAP. There were no significant differences between the optimal CPAP level achieved with full PSG or with auto-CPAP. As a secondary analysis, we analyzed auto-CPAP performance with regard to sleep-stage distribution and arousals in a group of nine male patients, and compared it with the previous group of 20 patients in which manually CPAP titration was guided by PSG. After adequate CPAP was reached, upward and downward fluctuations in the CPAP level had no significant effect on sleep architecture or fragmentation. We conclude that auto-CPAP permits the prediction of future fixed-level CPAP needs, and does so without sleep disruption.
Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma
Authors: Diana M. Stafforini, Toshio Numao, Alexander Tsodikov, Darius Vaitkus, Takeshi Fukuda, Naoto Watanabe, Naoto Fueki, Thomas M. McIntyre, Guy A. Zimmerman, Sohei Makino, Stephen M. Prescott
Journal: Journal of Clinical Investigation (1999)

Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.