tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Frequent In-Center Hemodialysis
Authors: Chris P. Lee, Stefanos A. Zenios, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2008)

Published evidence suggests that frequent hemodialysis (more than three times per week) for patients with ESRD may improve health-related quality of life and has the potential to increase longevity and reduce hospitalization and other complications. Here, a Monte Carlo simulation model was used to compare varying combinations of in-center hemodialysis frequency (three to six treatments per week) and session length (2 to 4.5 h per session) with regard to unadjusted and quality-adjusted life-years and total lifetime costs for a cohort of 200,000 patients, representing the prevalent ESRD population. The incremental cost-effectiveness ratio was calculated for the various regimens relative to a conventional hemodialysis regimen (three treatments per week, 3.5 h per session). Using conservative assumptions of the potential effects of more frequent hemodialysis on outcomes, most strategies achieved a cost-effectiveness ratio of <$125,000, although all had a cost-effectiveness ratio of >$75,000. The cost-effectiveness ratio increased with the frequency of hemodialysis. More frequent in-center hemodialysis strategies could become cost-neutral if the cost per hemodialysis session could be reduced by 32 to 43%. No other change in model assumptions achieved cost neutrality. In conclusion, given the extraordinarily high costs of the ESRD program, the viability of more frequent hemodialysis strategies depends on significant improvements in the economic model underlying the delivery of hemodialysis.
<sup>11</sup>C-Acetate Positron Emission Tomography Imaging and Image Fusion With Computed Tomography and Magnetic Resonance Imaging in Patients With Recurrent Prostate Cancer
Authors: Stefan Wachter, Sandra Tomek, Amir Kurtaran, Natascha Wachter-Gerstner, Bob Djavan, Alexander Becherer, Markus Mitterhauser, Georg Dobrozemsky, Shuren Li, Richard Pötter, Robert Dudczak, Kurt Kletter
Journal: Journal of Clinical Oncology (2006)

To assess the clinical value of computed tomography (CT) and magnetic resonance imaging (MRI) image fusion with 11C-acetate (AC) positron emission tomography (PET) imaging for detection and exact location of clinically occult recurrences.Fifty prostate cancer patients with elevated/increasing serum prostate-specific antigen levels after radical therapy underwent whole-body AC PET. Uptake was initially interpreted as normal, abnormal, or equivocal. In case of abnormal or equivocal uptake, additional conventional imaging techniques, such as CT, MRI, and bone scans, were performed. To precisely define the anatomic location of abnormal uptake and to improve characterization of equivocal lesions, a software-assisted image fusion (CT-PET, MRI-PET) was performed and evaluated as site-by-site analysis of 51 abnormal (n = 37) or equivocal (n = 14) sites of all 50 patients. In 17 patients, additional histopathologic evaluation was available.In five (10%), 13 (26%), and 32 (64%) of the 50 patients, AC PET studies demonstrated AC uptake judged as normal, equivocal, and abnormal, respectively. Image fusion changed characterization of equivocal lesions as normal in five (10%) of 51 sites and abnormal in nine (18%) of 51 sites. It precisely defined the anatomic location of abnormal uptake in 37 (73%) of 51 sites. AC PET findings did influence patient management in 14 (28%) of 50 patients.Retrospective fusion of AC PET and CT/MRI is feasible and seems to be essential for final diagnosis. This is particularly true in patients with AC uptake in the prostate region.
Palliation of symptoms in non-small cell lung cancer: a study by the Yorkshire Regional Cancer Organisation Thoracic Group.
Authors: M F Muers, C E Round
Journal: Thorax (1993)

BACKGROUND--Although most treatment for non-small cell lung cancer is palliative, data on the adequacy of symptom control are scanty and there has been little discussion about the appropriate indices. METHODS--Two hundred and eighty nine unselected patients presenting sequentially to six specialists were studied; 242 cases were confirmed histologically and all were managed as non-small cell lung cancer. At presentation and two monthly for one year or until death each of 12 symptoms was graded by a physician at a clinic interview on a four point scale as absent, mild, moderate, or severe. For each symptom a palliative index (median duration of control/median duration of survival) was calculated, where control was defined as an improvement in symptoms of any severity by one grade or more. RESULTS--Sixty four (22%) patients had surgery, 15 (5%) radical and 107 (37%) palliative radiotherapy, and 103 (36%) best supportive care. Analysis showed that most symptoms inexorably worsened with time. The palliation index for haemoptysis was 86%, chest pain 73%, cough 34%, and breathlessness 30%; for systemic symptoms it was 54% for anorexia and 47% for malaise. Palliation was poor in many patients after surgery. Breathlessness was a particular problem in the group having best supportive care. CONCLUSIONS--The frequency of most symptoms in non-small cell lung cancer increases inexorably with time until malaise and anorexia are almost universal. Haemoptysis and chest pain are better palliated than cough and breathlessness. Present treatments fail to give adequate palliation for many patients, and the emphasis in future therapeutic studies should be on the relief of the more severe symptoms.
Role of hypoxia-induced anorexia and right ventricular hypertrophy on lactate transport and MCT expression in rat muscle
Authors: Guillaume Py, Nicolas Eydoux, Karen Lambert, Rachel Chapot, Natahlie Koulmann, Hervé Sanchez, Lahoucine Bahi, André Peinnequin, Jacques Mercier, André-Xavier Bigard
Journal: Metabolism (2005)
Functional genomics and rheumatoid arthritis: where have we been and where should we go?
Authors: James N Jarvis, Mark Barton Frank
Journal: Genome Medicine (2010)

Studies in model organisms and humans have begun to reveal the complexity of the transcriptome. In addition to serving as passive templates from which genes are translated, RNA molecules are active, functional elements of the cell whose products can detect, interact with, and modify other transcripts. Gene expression profiling is the method most commonly used thus far to enrich our understanding of the molecular basis of rheumatoid arthritis in adults and juvenile idiopathic arthritis in children. The feasibility of this approach for patient classification (for example, active versus inactive disease, disease subsets) and improving prognosis (for example, response to therapy) has been demonstrated over the past 7 years. Mechanistic understanding of disease-related differences in gene expression must be interpreted in the context of interactions with transcriptional regulatory molecules and epigenetic alterations of the genome. Ongoing work regarding such functional complexities in the human genome will likely bring both insight and surprise to our understanding of rheumatoid arthritis.
Serotonin Receptors, Novel Targets of Sulforaphane Identified by Proteomic Analysis in Caco-2 Cells
Authors: Lina Mastrangelo, Aedin Cassidy, Francis Mulholland, Wei Wang, Yongping Bao
Journal: Cancer Research (2008)

Abstract Cancer chemopreventive activity of sulforaphane has been predominantly associated with its ability to induce phase II detoxification enzymes. In the present study, novel targets of sulforaphane were identified and characterized using a proteomics approach. Two-dimensional gel electrophoresis and mass spectrometry were used to produce protein profiles of human colon adenocarcinoma Caco-2 cells treated with 5 μmol/L sulforaphane for 48 h and control cells (0.05% DMSO). Gel comparisons showed the down-regulation to undetectable level of the serotonin receptor 5-HT3 after sulforaphane treatment. In addition, Aldo-keto reductase and d-dopachrome decarboxylase were also differentially expressed in control and treated cell extracts. To elucidate two-dimensional gel findings, the neurotransmitter receptors 5-HT3A, 5-HT1A, 5-HT2C, and the serotonin reuptake transporter were analyzed using Western blotting. Results showed a decrease of neurotransmitter receptors in a dose-dependent manner after sulforaphane treatment. Moreover, after exposure of Caco-2 cells to sulforaphane, nicotinic acetylcholine receptor protein level was increased. These findings suggested a potential effect of sulforaphane on serotonin release. Activation of neurotransmitter receptors followed by initiation of cyclic AMP signaling might be crucial events in colon carcinoma progression. Thus, the effect of sulforaphane may help to elucidate signaling pathways serotonin-mediated in colon cancer and lead to development of potential novel therapeutic agents. [Cancer Res 2008;68(13):5487–91]
Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data
Authors: G. A. Knoll, M. B. Kokolo, R. Mallick, A. Beck, C. D. Buenaventura, R. Ducharme, R. Barsoum, C. Bernasconi, T. D. Blydt-Hansen, H. Ekberg, C. R. Felipe, J. Firth, L. Gallon, M. Gelens, D. Glotz, J. Gossmann, M. Guba, A. A. Morsy, R. Salgo, E. H. Scheuermann, H. Tedesco-Silva, S. Vitko, C. Watson, D. A. Fergusson
Journal: BMJ (2014)

<b>Objective</b> To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus. <b>Design</b> Systematic review and meta-analysis of individual patient data. <b>Data sources</b> Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013. <b>Eligibility</b> Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival. <b>Results</b> The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. The most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls. <b>Conclusions</b> Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.
Pilot Study of a Heptavalent Vaccine-Keyhole Limpet Hemocyanin Conjugate plus QS21 in Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer
Authors: Paul J. Sabbatini, Govind Ragupathi, Chandra Hood, Carol A. Aghajanian, Margrit Juretzka, Alexia Iasonos, Martee L. Hensley, Maria K. Spassova, Ouathek Ouerfelli, David R. Spriggs, William P. Tew, Jason Konner, Henrik Clausen, Nadeem Abu Rustum, Samuel J. Dansihefsky, Philip O. Livingston
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. Experimental Design: Eleven patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 μg), Globo-H (10 μg), Lewis Y (10 μg), Tn(c) (3 μg), STn(c) (3 μg), TF(c) (3 μg), and Tn-MUC1 (3 μg) individually conjugated to KLH and mixed with adjuvant QS21(100 μg). Vaccinations were administered at weeks 1, 2, 3, 7, and 15. Periodic blood and urine samples were obtained to monitor safety (complete blood count, comprehensive panel, amylase, thyroid-stimulating hormone, and urinalysis) and antibody production (ELISA, fluorescence-activated cell sorting, and complement-dependent cytotoxicity). Results: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2 in two patients), fever, myalgia, and localized injection site reactions were most frequent. No clinically relevant hematologic abnormalities were noted. No clinical or laboratory evidence of autoimmunity was seen. Serologic responses by ELISA were largely IgM against each antigen with the exception of Tn-MUC1 where both IgM and IgG responses were induced. Antibody responses were generally undetectable before immunization. After immunization, median IgM titers were as follows: Tn-MUC1, 1:640 (IgG 1:80); Tn, 1:160; TF, 1:640; Globo-H, 1:40; and STn, 1:80. Only one response was seen against Lewis Y; two were against GM2. Eight of nine patients developed responses against at least three antigens. Antibody titers peaked at weeks 4 to 8 in all patients. Fluorescence-activated cell sorting and complement-dependent cytotoxicity analysis showed substantially increased reactivity against MCF7 cells in seven of nine patients, with some increase seen in all patients. Conclusions: This heptavalent-KLH conjugate plus QS21 vaccine safely induced antibody responses against five of seven antigens. Investigation in an adequately powered efficacy trial is warranted.
First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer
Authors: B. Thürlimann, K. Beretta, M. Bacchi, M. Castiglione-Gertsch, A. Goldhirsch, W.F. Jungi, F. Cavalli, H.-J. Senn, M. Fey, T. Löhnert
Journal: Annals of Oncology (1996)
Comparison of Different Measures of Urinary Protein Excretion for Prediction of Renal Events
Authors: Hiddo J. Lambers Heerspink, Ron T. Gansevoort, Barry M. Brenner, Mark E. Cooper, Hans Henrik Parving, Shahnaz Shahinfar, Dick de Zeeuw
Journal: Journal of the American Society of Nephrology (2010)

There are many methods to screen for abnormal amounts of proteinuria to identify patients at risk for progression of renal disease, but which method best predicts renal risk is unknown. Here, we analyzed a subset of 701 patients with type 2 diabetes and nephropathy participating in the Reduction of Endpoints in Non Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial to compare the ability of urinary protein excretion (UPE) and urinary albumin excretion (UAE) from a 24-hour urine collection and urinary albumin concentration (UAC) and the albumin:creatinine ratio (ACR) from a first-morning void in predicting renal events. The primary outcome measure was the time to a doubling of serum creatinine or end-stage renal disease. During follow-up, 202 events occurred. The hazard ratios for the risk of a renal outcome (95% CIs) associated with 1-SD increment in the log-transformed measures were 3.16 (2.60 to 3.86) for UAE, 3.02 (2.53 to 3.62) for UPE, 3.23 (2.67 to 3.91) for UAC, and 4.36 (3.50 to 5.45) for ACR. The area under the ROC curve was significantly higher for ACR compared with the other measures. In conclusion, measurement of the albumin:creatinine ratio in a first-morning void is the superior method to predict renal events in patients with type 2 diabetes and nephropathy.
Long-Term Follow-Up of High-Risk Allogeneic Peripheral-Blood Stem-Cell Transplant Recipients: Graft-Versus-Host Disease and Transplant-Related Mortality
Authors: R. A. Brown, D. Adkins, H. Khoury, R. Vij, L. T. Goodnough, S. Shenoy, J. F. DiPersio
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine the risks of graft-versus-host disease (GVHD) and transplant-related mortality after allogeneic peripheral-blood stem-cell (PBSC) transplantation. PATIENTS AND METHODS: Between December 1994 and July 1996, 50 consecutive patients with high-risk hematologic malignancies in first remission or relapse received high-dose therapy followed by transplantation of granulocyte colony-stimulating factor–mobilized, allogeneic PBSCs collected from HLA-identical siblings. GVHD prophylaxis included cyclosporine and corticosteroids. RESULTS: As of April 1, 1998, 18 patients (36% ± 13%) survived with a median follow-up period of 767 days (range, 602 to 1,127 days). The actuarial probability of grades 2-4 acute GVHD was 0.37 ± 0.14 (95% confidence interval). Of 36 assessable patients, 26 (72% ± 15%) developed chronic GVHD. The actuarial probability of chronic GVHD 2 years after transplantation was 0.87 ± 0.15. Of 14 progression-free survivors, 11 (79% ± 22%) have active, chronic GVHD. All 11 patients require ongoing immunosuppression, and nearly two thirds have extensive disease. Thirteen patients died as a result of transplant-related mortality (26% ± 12%), six (12%) before and seven (14%) after day +100. CONCLUSION: We observed a high risk of chronic GVHD after allogeneic PBSC transplantation, which compromised the performance status of most long-term survivors and resulted in a relatively high risk of late transplant-related mortality. Approximately 75% of transplant-related deaths were associated with GVHD; thus, reduction in transplant-related mortality after allogeneic PBSC transplantation will require more effective strategies for the prophylaxis and/or treatment of GVHD.
The logrank test
Authors: J Martin Bland, Douglas G Altman
Journal: BMJ (2004)

We often wish to compare the survival experience of two (or more) groups of individuals. For example, the table shows survival times of 51 adult patients with recurrent malignant gliomas1 tabulated by type of tumour and indicating whether the patient had died or was still alive at analysis—that is, their survival time was censored.2 As the figure shows, the survival curves differ, but is this sufficient to conclude that in the population patients with anaplastic astrocytoma have worse survival than patients with glioblastoma?

View this table:

Weeks to death or censoring in 51 adults with recurrent gliomas1 (A=astrocytoma, G=glioblastoma)





Fig 1 
Survival curves for women with glioma by diagnosis



We could compute survival curves3 for each group and compare the proportions surviving at any specific time. The weakness of this approach is that it does not provide a comparison of the total survival experience of the two groups, but rather gives a comparison at some arbitrary time point(s). In the figure the difference in survival is greater at some times than others and eventually becomes …
Methylation of HPV18, HPV31, and HPV45 Genomes and Cervical Intraepithelial Neoplasia Grade 3
Authors: Nicolas Wentzensen, Chang Sun, Arpita Ghosh, Walter Kinney, Lisa Mirabello, Sholom Wacholder, Ruth Shaber, Brandon LaMere, Megan Clarke, Attila T. Lorincz, Philip E. Castle, Mark Schiffman, Robert D. Burk
Journal: JNCI Journal of the National Cancer Institute (2012)

Persistent infections with carcinogenic human papillomavirus (HPV) types are the necessary cause of cervical cancer. We recently demonstrated that the HPV16 genome is strongly methylated in cervical precancer compared with transient infections. However, the extent of methylation in other HPV types and its role in progression to cancer is poorly understood. We analyzed whole-genome methylation patterns of the three next most carcinogenic HPV genotypes: HPV31 (closely related to HPV16), and two other closely related types, HPV18 and HPV45. DNA was extracted from cervical cytology specimens from 92 women with precancer and 96 women infected with HPV31, HPV18, or HPV45, but who had no cytological or histological abnormalities. After bisulfite modification, genome-wide pyrosequencing was performed covering 80–106 sites. We calculated differences in median methylation, odds ratios, areas under the curve, and Spearman rank correlation coefficients for methylation levels between different sites. All statistical tests were two-sided. For all three HPV types, we observed strongly elevated methylation levels at multiple CpG sites in the E2, L2, and L1 regions among women with cervical intraepithelial neoplasia grade 3 compared with women with transient infections. We observed high correlation of methylation patterns between phylogenetically related types. The highest areas under the curve were 0.81 for HPV31, 0.85 for HPV18, and 0.98 for HPV45. Differential methylation patterns in cervical intraepithelial neoplasia grade 3 patients with multiple infections suggest that methylation can clarify which of the infections is causal. Carcinogenic HPV DNA methylation indicates transforming HPV infections. Our findings show that methylation of carcinogenic HPV types is a general phenomenon that warrants development of diagnostic assays.
Reducing Hospital Errors: Interventions that Build Safety Culture
Authors: Sara J. Singer, Timothy J. Vogus
Journal: Annual Review of Public Health (2013)

Hospital errors are a seemingly intractable problem and continuing threat to public health. Errors resist intervention because too often the interventions deployed fail to address the fundamental source of errors: weak organizational safety culture. This review applies and extends a theoretical model of safety culture that suggests it is a function of interrelated processes of enabling, enacting, and elaborating that can reduce hospital errors over time. In this model, enabling activities help shape perceptions of safety climate, which promotes enactment of safety culture. We then classify a broad array of interventions as enabling, enacting, or elaborating a culture of safety. Our analysis, which is intended to guide future attempts to both study and more effectively create and sustain a safety culture, emphasizes that isolated interventions are unlikely to reduce the underlying causes of hospital errors. Instead, reducing errors requires systemic interventions that address the interrelated processes of safety culture in a balanced manner.
B Cells Limit Repair after Ischemic Acute Kidney Injury
Authors: Hye Ryoun Jang, Maria Teresa Gandolfo, Gang Jee Ko, Shailesh R. Satpute, Lorraine Racusen, Hamid Rabb
Journal: Journal of the American Society of Nephrology (2010)

There is no established modality to repair kidney damage resulting from ischemia-reperfusion injury (IRI). Early responses to IRI involve lymphocytes, but the role of B cells in tissue repair after IRI is unknown. Here, we examined B cell trafficking into postischemic mouse kidneys and compared the repair response between control (wild-type) and muMT (B cell-deficient) mice with and without adoptive transfer of B cells. B cells infiltrated postischemic kidneys and subsequently activated and differentiated to plasma cells during the repair phase. Plasma cells expressing CD126 increased and B-1 B cells trafficked into postischemic kidneys with distinct kinetics. An increase in B lymphocyte chemoattractant in the kidney preceded B cell trafficking. Postischemic kidneys of muMT mice expressed higher IL-10 and vascular endothelial growth factor and exhibited more tubular proliferation and less tubular atrophy. Adoptive transfer of B cells into muMT mice reduced tubular proliferation and increased tubular atrophy. Treatment with anti-CD126 antibody increased tubular proliferation and reduced tubular atrophy in the late repair phase. These results demonstrate that B cells may limit the repair process after kidney IRI. Targeting B cells could have therapeutic potential to improve repair after IRI.