tbuckley/cabot-search huggingface dataset:
Interim analysis of the largest prospective trial to date in adult CD20-positive post-transplant lymphoproliferative disorder (PTLD): Introducing risk-stratified sequential treatment (RSST).
Authors: Ralf Ulrich Trappe, Daan Dierickx, Petra Reinke, Ruth Neuhaus, Franck Morschhauser, Jan M. Zaucha, Peter Mollee, Heiner Zimmermann, Martin H. Dreyling, Ulrich Duehrsen, Gregor E.G. Verhoef, Hans Lehmkuhl, Marion Subklewe, Andreas Huettmann, Thomas Tousseyn, Corrado Tarella, Veronique Leblond, Ioannis Anagnostopoulos, Hanno Riess, Sylvain Choquet
Journal: Journal of Clinical Oncology (2012)

8030 Background: The prospective, multicenter international phase II PTLD-1 trial of sequential treatment (ST, 4 cycles of weekly rituximab followed by 4 cycles of CHOP-21 + G-CSF) in adult CD20-positive PTLD demonstrated excellent efficacy (90% overall response rate, ORR) and safety (11% treatment-related mortality, TRM). As the response to rituximab predicted overall survival (OS), the trial was amended in 2007 introducing risk-stratified sequential treatment (RSST) according to the response to rituximab (NCT00590447). Methods: Following rituximab on days 1, 8, 15 and 22, RSST consisted of 4 3-weekly courses of rituximab monotherapy for patients (pts) in complete remission (CR, low risk) while all others (high risk) received 4 cycles of R-CHOP-21 + G-CSF. Key exclusion criteria were CNS involvement, HIV infection, severe organ dysfunction not related to PTLD, and ECOG &gt; 2. Primary endpoint was ORR. This is an analysis of the first 91 patients treated with RSST. Results: 79/91 pts had monomorphic, 12 polymorphic PTLD. 41/91 pts were kidney, 27 liver, 12 heart, 7 lung or heart+lung, 3 heart+kidney and 1 kidney+pancreas transplant recipients. Median age at diagnosis was 60 years (range 20-82). 73/91 pts had late PTLD and 39/85 PTLDs were EBV-associated. 1 pt died before initiation of treatment; 5 pts discontinued treatment after 4 cycles rituximab. TRM of RSST was 7/90 (8%) including 5 deaths with unknown remission status. ORR was thus 74/80 (93%, 95%CI: 84-97%; CR: 62/80 [78%]). 24/90 pts (27%) achieved CR with 4 cycles of rituximab. After a median follow up of &gt;3 years, relapse rate in low risk pts was not increased by rituximab consolidation in RSST compared to CHOP consolidation in ST (3/23 vs. 5/14, p=0.104]). In patients in PD after rituximab, R-CHOP was more effective than CHOP in achieving CR (15/23 vs. 3/11, p=0.038). OS at 3 years was higher with RSST (70%, 95% CI: 60-82%) compared to ST (61%, 95%CI 49-72%) but this difference was not significant. Conclusions: With RSST 27% of pts were classified as low risk and achieved durable tumor control without chemotherapy while R-CHOP seems more efficient than CHOP in in high risk patients.
Abstract 3: Human CD34+ Cells Deficient in miR-377 Attenuates Cardiac Dysfunction and Repair After Ischemia-reperfusion Injury
Authors: Darukeshwara Joladarashi, Rajarajan A Thandavarayan, Sahana Suresh Babu, Prince Jeyabal, Shashirekha Krishnamurthy, Venkata Naga Srikanth Garikipati, Suresh Verma, Alexander Mackie, Mohnsin Khan, Erin Vaughan, Raj Kishore, Prasanna Krishnamurthy
Journal: Circulation Research (2015)

microRNAs (miRNA/miR) dysregulation has been implicated in cardiac remodeling after injury or stress, however its effects on Human CD34 + cells (hCD34 + ) biology and function, particularly in the context of cell-based therapy for cardiomyopathy is not fully understood. miRNA array data analysis indicates that miR-377 is a potential interest. pre-miR-377 transfection in EPCs inhibits their migration and vascular tube formation ability in HUVECs. Furthermore, hCD34 + cells treated with miR-377 mimic showed decrease in expression of STK35 (a novel serine/threonine kinase). Moreover, STK35 is predicted as a potential target gene of miR-377 by computational analysis. Interestingly, in a relevant mouse model of ischemia reperfusion, intramyocardial transplantation of miR-377-silenced hCD34 + cells promotes neovascularization leading to improvement in myocardial function and repair. Echocardiography showed LV function was significantly improved in mice receiving miR-377-silenced hCD34 + cells compared to control-miR-transfected hCD34 + cells. Taken together, these data suggest that inhibiting miR-377 in hCD34 + cells promotes their angiogenic ability after transplantation into ischemic myocardial tissue, potentially through activation of STK35 signaling.
Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease
Authors: Lauranne A.A.P. Derikx, Lisa J.T. Smits, Shannon van Vliet, Evelien Dekker, Cora M. Aalfs, Mariëtte C.A. van Kouwen, Fokko M. Nagengast, Iris D. Nagtegaal, Nicoline Hoogerbrugge, Frank Hoentjen
Journal: Clinical Gastroenterology and Hepatology (2016)
Successful Treatment of Hepatic Metastases of Hormone Refractory Prostate Cancer Using Radioligand Therapy With 177Lu-PSMA-617
Authors: Xiao Wei, Carl Schlenkhoff, Claudia Sopora, Markus Essler, Hojjat Ahmadzadehfar
Journal: Clinical Nuclear Medicine (2016)

An 81-year-old castrate-resistant prostate cancer man with multiple lymph node, bone, and hepatic metastases received four cycles of Lu-PSMA-617 treatments at our department from May to December 2015. All of his liver metastases showed PSMA expression in Ga-PSMA PET performed before the first cycle. Under this therapy, all of the metastases showed significant regression in size and PSMA expression over time.
Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza <i>S. aureus</i> pneumonia
Authors: Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, Geoffrey A. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger
Journal: The Journal of Experimental Medicine (2016)

Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased necrotic death of inflammatory cells, thereby resulting in lethal damage to surrounding tissue. Collectively, our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation. This disruption leads to not only increased susceptibility to S. aureus infection, but also extensive lung damage. Importantly, we show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from coinfection. These findings suggest that treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia.
Nonmyeloablative (NMA), HLA-Mismatched Unrelated Donor (mMUD) BMT with High-Dose Posttransplantation Cyclophosphamide (PTCy) Has Outcomes Similar to Matched BMT
Authors: Yvette L. Kasamon, Ephraim J. Fuchs, Javier Bolaños-Meade, Mary S. Leffell, Marianna Zahurak, Gary L. Rosner, Jonathan D. Powell, Richard F. Ambinder, Richard J. Jones, Leo Luznik
Journal: Blood (2015)
Targeting the NRF2/HO-1 Antioxidant Pathway with Consequences for Notch Signaling in FLT3-ITD Positive AML: A Novel Therapeutic Approach
Authors: Marisa J Hornbaker, Mary E Irwin, LaNisha Patterson, Shelley M Herbrich, Patrick Zweidler-McKay, Joya Chandra
Journal: Blood (2015)
Outcome of Mildly Symptomatic or Asymptomatic Obstructive Hypertrophic Cardiomyopathy
Authors: Paul Sorajja, Rick A. Nishimura, Bernard J. Gersh, Joseph A. Dearani, David O. Hodge, Heather J. Wiste, Steve R. Ommen
Journal: Journal of the American College of Cardiology (2009)
Cost-Effectiveness of Sacubitril–Valsartan in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Alexander T. Sandhu, Daniel A. Ollendorf, Richard H. Chapman, Steven D. Pearson, Paul A. Heidenreich
Journal: Annals of Internal Medicine (2016)

Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction.To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure.Markov decision model.Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables.Patients at an average age of 64 years, New York Heart Association (NYHA) class II to IV heart failure, and left ventricular ejection fraction of 0.40 or less.Lifetime.Societal.Treatment with sacubitril-valsartan or lisinopril.Life-years, quality-adjusted life-years (QALYs), costs, heart failure hospitalizations, and incremental cost-effectiveness ratios.The sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29 203 in incremental costs, equating to a cost per QALY gained of $47 053. The cost per QALY gained was $44 531 in patients with NYHA class II heart failure and $58 194 in those with class III or IV heart failure.Sacubitril-valsartan treatment was most sensitive to the duration of improved outcomes, with a cost per QALY gained of $120 623 if the duration was limited to the length of the trial (median, 27 months). No variations in other parameters caused the cost to exceed $100 000 per QALY gained.The benefit of sacubitril-valsartan is based on a single clinical trial.Treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure.U.S. Department of Veterans Affairs and Institute for Clinical and Economic Review.
Reporting accelerometer methods in physical activity intervention studies: a systematic review and recommendations for authors
Authors: Alexander H K Montoye, Rebecca W Moore, Heather R Bowles, Robert Korycinski, Karin A Pfeiffer
Journal: British Journal of Sports Medicine (2016)

This systematic review assessed the completeness of accelerometer reporting in physical activity (PA) intervention studies and assessed factors related to accelerometer reporting.The PubMed database was used to identify manuscripts for inclusion. Included studies were PA interventions that used accelerometers, were written in English and were conducted between 1 January 1998 and 31 July 2014. 195 manuscripts from PA interventions that used accelerometers to measure PA were included. Manuscript completeness was scored using 12 questions focused on 3 accelerometer reporting areas: accelerometer information, data processing and interpretation and protocol non-compliance. Variables, including publication year, journal focus and impact factor, and population studied were evaluated to assess trends in reporting completeness.The number of manuscripts using accelerometers to assess PA in interventions increased from 1 in 2002 to 29 in the first 7 months of 2014. Accelerometer reporting completeness correlated weakly with publication year (r=0.24, p<0.001). Correlations were greater when we assessed improvements over time in reporting data processing in manuscripts published in PA-focused journals (r=0.43, p=0.002) compared to manuscripts published in non-PA-focused journals (r=0.19, p=0.021). Only 7 of 195 (4%) manuscripts reported all components of accelerometer use, and only 132 (68%) reported more than half of the components.Accelerometer reporting of PA in intervention studies has been poor and improved only minimally over time. We provide recommendations to improve accelerometer reporting and include a template to standardise reports.
To analyze the safety, efficacy, and toxicity profile of ixabepilone and capecitabine combination in metastatic breast cancer patients in Indian population.
Authors: U. Batra, D. Doval
Journal: Journal of Clinical Oncology (2010)

e11513 Background: With the increasing use of anthracyclines and taxanes in the adjuvant setting, improved survival of patients with breast cancer, there is an unmet need of developing second-line chemotherapeutic agents which can be used specially in the subset of HER2-negative patients. Methods: Patients had to have histologically proven breast cancer, at least one measurable disease, age >18 years, ECOG scale 0-2. Patients with CNS metastasis deranged LFT, estimated life survival less than three months were excluded. Ixabepilone was administered as 40 mg/m2 q 3 weekly and capecitabine as 850 mg/m2 bd for 14 days. Prophylactic growth factor support was not given. Patients were evaluated before treatment and subsequently every 3 cycles until progression. The primary end point was to assess time-to-tumor progression, toxicity profile, and quality of life. Results: 25 patients were analyzed. The median number of cycles received was 5. 15 patients had partial response whereas 2 patients achieved complete response. 5 patients had stable disease whereas 3 patients had progressive disease. 3 patients could not tolerate the combination therapy and had to discontinue treatment. The median time-to-tumor progression was 5.8 months. Grade 3 or 4 toxicities included neutropenia (22%), fatigue (33%), anorexia (22%), and neuropathy (41%). The incidence of hand foot syndrome was 30%. The most distressing symptom was neuropathy and hand foot syndrome. Conclusions: The combination of ixabepilone and capecitabine, though effective, is associated with significant neuropathy and hematological toxicity. A lot of research needs to be done to develop new chemotherapeutic agents that are equally efficacious, cost effective, and maintain a good quality of life for the patients. No significant financial relationships to disclose.
A significant dietary change after breast cancer diagnosis: Early results of a United Kingdom prospective multicenter study.
Authors: L. S. Velentzis, J. V. Woodside, M. M. Cantwell, A. J. Leathem, M. R. Keshtgar
Journal: Journal of Clinical Oncology (2010)

1588 Background: DietCompLyf, a prospective United Kingdom study, is investigating the effects of phytoestrogens and other lifestyle factors on survival in patients with invasive breast cancer. We present here a comparison of pre- and post-diagnostic dietary intake and supplement use reported by 1760 participants. Methods: Twosemi-quantitative food frequency questionnaires were administered to participants at study entry (approximately one year after diagnosis) one representing usual diet before diagnosis and the other, after diagnosis until study recruitment. Consumption of food groups and daily intake of macro- and micro-nutrients derived by nutritional software program analysis was evaluated. Supplement use was also examined. Results: Consumption of fruit and vegetables, lean protein sources, tea, wholegrain foods and nuts was significantly increased post-diagnosis (p < 0.05). Concurrently, intake of red meat, refined grain products, high-fat and high-sugar foods, coffee and some alcoholic drinks was significantly decreased (p < 0.05). Dietary intake of retinol and calcium decreased after diagnosis but intake of other vitamins and minerals increased (p < 0.05). Supplement use was prevalent in this cohort with 59% reporting use before diagnosis. A change in behaviour was observed following diagnosis with 10.3% of women stopping all supplements and 15.3% starting use. Fish oils, multivitamin and mineral products, evening primrose oil, vitamin C, glucosamine, calcium and estrogenic botanical supplements (EBS) were most commonly used with increases after diagnosis being statistically significantly (p < 0.05). A third of named EBS referred to use for menopausal or hormone-related symptoms. Flaxseed, isoflavone containing supplements, ginseng, and red clover were the most popular. 3.6% of participants took EBS before diagnosis, but numbers of users increased significantly (9.7%) following diagnosis. Conclusions: British women participating in DietCompLyf made significant dietary changes following their breast cancer diagnosis. It is important for clinicians to be aware of this change in attitude so as to inform and encourage their patients to make healthier post-diagnostic lifestyle choices. No significant financial relationships to disclose.
Rural-urban disparity in cancer screening among elder Medicare beneficiaries: Does rurality matter?
Authors: L. Fan, S. G. Mohile, K. Noyes
Journal: Journal of Clinical Oncology (2010)

6085 Background: Studies indicate urban-rural disparity in cancer screenings. It is unclear if the disparity exists among Medicare beneficiaries. Further, few studies have assessed rurality's impacts on receipt of screenings for different cancers. Objective: To examine urban-rural disparity of screening for breast cancer (BC) and colorectal cancer (CRC) among elder Medicare beneficiaries and assess rurality's independent impact on receipt of screenings. Methods: We included community dwelling beneficiaries aged > 65 from 2005 Medicare Current Beneficiary Survey (MCBS). 4 categories of rural and urban status were created using Rural-Urban Commuting Area Codes (RUCAs). Self report screenings including mammogram in last year and fecal occult blood test (FOBT) in last year or colonoscopy/sigmiodoscopy in past 5 years were compared among the 4 areas; the independent impact of rurality was evaluated using weighted logistic regression. Results: 53.0% (95% CI: 51.1%-54.8%) of urban beneficiaries, 51.8% (95% CI: 47.3%-56.3%) of those from large rural, 45.2% (95% CI: 37.5%-52.9%) from small rural, and 44.0% (95% CI: 38.8%-49.1%) from isolated rural areas had mammogram last year (p = 0.011); 55.5% (95% CI: 53.7%-57.2%) of urban beneficiaries, 50.1% (95% CI: 45.2%-54.9%) of those from large rural, 47.5% (95% CI: 43.0%-52.0%) from small rural, and 42.7% (95% CI: 38.3%-47.0%) from isolated rural areas had FOBT in last year or colonoscopy or sigmiodoscopy in past 5 years (p < 0.001). After controlling for age, gender, and race, rurality is significantly associated with screenings for BC (p = 0.015) and CRC (p < 0.001). After further controlling for income, education, health insurance, HMO, and health conditions, rurality is significantly associated with CRC screening (p < 0.001), but not BC screening (p = 0.164). Conclusions: There is evidence of urban-rural disparity for both BC and CRC. SES and health status totally eliminated the disparity for BC screening but not for CRC screening. Health promotions to improve cancer screening should focus more on small and isolated rural. For BC screening, programs aiming at SES mechanism (income, education, and health insurance) will most likely reduce the disparity to a great extent. No significant financial relationships to disclose.
A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy
Authors: Mark Haas, Jacobien C. Verhave, Zhi-Hong Liu, Charles E. Alpers, Jonathan Barratt, Jan U. Becker, Daniel Cattran, H. Terence Cook, Rosanna Coppo, John Feehally, Antonello Pani, Agnieszka Perkowska-Ptasinska, Ian S.D. Roberts, Maria Fernanda Soares, Hernan Trimarchi, Suxia Wang, Yukio Yuzawa, Hong Zhang, Stéphan Troyanov, Ritsuko Katafuchi
Journal: Journal of the American Society of Nephrology (2016)

The Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m 2 and median (interquartile range) proteinuria of 1.2 (0.7–2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in over one fourth of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.
Increasing Age and Survival After Bone Marrow Transplant-Reply
Authors: Mary M. Horowitz
Journal: JAMA (1993)

<h3>In Reply.</h3> —The conclusion that age does not adversely affect outcome after allogeneic bone marrow transplantation in patients with leukemia is based on our findings in patients with early and intermediate disease. In these groups, the leukemia-free survival rate (95% confidence interval) at 2 years was 57% (37% to 75%) and 25% (6% to 65%), respectively. This is not significantly different from the corresponding figures of 51% (47% to 55%) and 32% (26% to 39%) in patients 30 to 39 years of age. The small numbers of subjects 50 years and older with advanced leukemia limited our ability to detect differences in this group. This we indicated in our report. Based on Karnofsky scores, duration of disease, and absence of infection prior to transplant, we found no evidence of a selection bias in transplant recipients older than 50 years compared with younger patients. However, transplant recipients are a select group,
Base Excision Repair Glycosylase Activity Is Impaired in a Subgroup of Acute Myeloid Leukemia Resulting in Increased Levels of Oxidative Base Lesions
Authors: Werner Olipitz, Karin Lind, Nicole Monsberger, Anna Katschnig, Aswin Mangerich, Sybille Hofer, Eduard Schulz, Franz Quehenberger, Dietmar Schlembach, Christoph Robier, Albert Woelfler, Armin Zebisch, Heinz Sill
Journal: Blood (2014)