tbuckley/cabot-search huggingface dataset:
Incidence of adenocarcinoma in Barrett's esophagus: Results of a multicenter prospective study
Authors: H. S. Garewal, S.-H. Ahn, R. E. Sampliner, G. W. Falk, M. B. Fennerty, L. Camargo, J. M. Guillen
Journal: Journal of Clinical Oncology (2004)

4001 Background: Barrett's esophagus (BE) is associated with increased cancer risk. However, estimates of the cancer incidence in BE have generally been based on retrospective studies or retrospective cohort analyses that are strictly not prospective. The aim of this study was to prospectively follow a cohort of cancer-free patients with BE to estimate the incidence of esophageal adenocarcinoma based on follow-up procedures used for the diagnosis of cancer being performed as per standard clinical care. Methods: From January 1994 thru September of 1998, 161 patients were initially enrolled in a BE surveillance program, and had at least two serial endoscopies with biopsies and more than one year of follow up. As usual surveillance, four-quadrant biopsies were taken from the Barrett's epithelium at 2-cm intervals with additional samples obtained from any suspicious lesions. Patients with cancers at diagnosis or those developing cancer within 6 months of the initial visit were excluded as they were considered to have prevalent cancers. Results: To date, 367 endoscopies have been performed in these 161 patients, with mean follow-up of 4.3 years (range 1–16 years), yielding a total of 695 patient-years of follow-up. The mean age at the time of the diagnosis of BE was 62.9 years. Short-segment BE accounted for 52 of the 161 patients (32%). Only two patients developed adenocarcinoma (at year 6 and 12 from diagnosis), yielding an incidence rate of one adenocarcinoma per 347.5 patient-years of follow-up. The length of BE lesion did not significantly change over time. Patients developing high grade dysplasia or adenocarcinoma had a significantly longer length of BE (mean 7.6cm) than those without dysplasia or with low grade dysplasia (mean 4.6cm) (p=0.0193). Conclusions: This is the first prospective follow-up study of cancer risk in BE. The incidence of adenocarcinoma in patients with BE is lower than in previously reported retrospective cohort studies. It also confirms previous findings that the length of BE lesion does not change significantly over time. The development of high grade dysplasia and cancer is strongly correlated with lesion length. No significant financial relationships to disclose.
Feasibility and Toxicity of a Modified Dose Intensive R- CODOX-M/IVAC for HIV-Associated Burkitt and Atypical Burkitt Lymphoma(BL): Preliminary Results of a Prospective Multicenter Phase II Trial of the AIDS Malignancy Consortium (AMC).
Authors: Ariela Noy, Lawrence Kaplan, Jeannette Lee
Journal: Blood (2009)
A Phase I Trial of a Pharmacodynamically-Conceived Decitabine and Thioguanine Combination in Patients with Advanced Myeloid Malignancies
Authors: Todd Rosenblat, Mark L. Heaney, Joseph G Jurcic, Azra Raza, John G. Mears, Ruth Santos, Diana Carrillo, David Shum, Jacquelyn Gonzales, Kevin Zikaras, Martin Santos, Rong Zhang, Glorymar Ibanezs, Leah Hogdal, Jennifer Crombie, Hakim Djaballah, Joseph M. Scandura, Anthony G. Letai, Mark G. Frattini
Journal: Blood (2014)
Abstract 16287: Effect of Transradial Catheterization on Patency Rates of Radial Arteries Used as a Conduit for Coronary Bypass
Authors: Mohammed Ruzieh, Ankush Moza, Pranav Diwan, Bhavana S Bangalore, Thomas Schwann, Jodi L Tinkel
Journal: Circulation (2015)

Title: Effect of transradial catheterization on patency rates of radial arteries used as a conduit for coronary bypass. Objective: To assess the difference in radial artery graft patency between patients who had the same radial artery used for angiography prior to bypass compared with those who did not. At present there are numerous studies looking at radial artery occlusion in situ after catheterization however very few studies looking at patency of the radial artery when used as a graft for CABG. Methods: A retrospective review was performed of all patients who underwent CABG at our institution in that past 15 years utilizing a radial artery graft (n= 570). Those who had subsequent imaging of the graft to evaluate patency by an angiogram or CT scan at any time were included for the study. 155 radial grafts were analyzed. The primary end point was evidence of occlusion at any point in follow up. Group A consisted of grafts in which the radial artery used for CABG had been utilized for angiography prior to CABG (n= 23). Group B consisted of grafts in which angiography was done via the femoral or contralateral radial approach (n= 132). Chi-square test was utilized to compare graft occlusion in these two groups. Statistical analyses was done using SPSS software. Results: The demographic characteristics of the patients in the two groups were similar. Occlusion of the radial artery graft was found to be more common in the group utilizing the same radial artery for angiography prior to CABG. The percentage of graft occlusion was 39 % (n= 9) in this group compared to 20 % in controls (n= 27). This difference showed a trend towards statistical significance with a p value of 0.05 Conclusion: Radial artery graft patency appears to be adversely affected by its utilization for angiography prior to CABG. Other patient, procedural and management dependent confounding factors may also affect graft patency and should be investigated in larger scale or randomized studies.
Successful Remission of Poor Prognosis AML after Adoptive Transfer and In Vivo Expansion of Human Haploidentical NK Cells.
Authors: Jeffrey S. Miller, Yvette Soignier, Angela Panosskaltsis-Mortari, David McKenna, Chap Le, Todd E. Defor, Linda J. Burns, Paul J. Orchard, Bruce R. Blazar, John E. Wagner, Arne Slungaard, Daniel J. Weisdorf, Ian J. Okazaki, Philip B. McGlave
Journal: Blood (2004)
Prospective validation of right ventricular role in primary graft dysfunction after lung transplantation
Authors: Purificación Pérez-Terán, Oriol Roca, José Rodríguez-Palomares, Juan C. Ruiz-Rodríguez, Ana Zapatero, Joaquim Gea, Joaquim Serra, Arturo Evangelista, Joan R. Masclans
Journal: European Respiratory Journal (2016)

Primary graft dysfunction is a significant cause of lung transplant morbidity and mortality, but its underlying mechanisms are not completely understood. The aims of the present study were: 1) to confirm that right ventricular function is a risk factor for severe primary graft dysfunction; and 2) to propose a clinical model for predicting the development of severe primary graft dysfunction.A prospective cohort study was performed over 14 months. The primary outcome was development of primary graft dysfunction grade 3. An echocardiogram was performed immediately before transplantation, measuring conventional and speckle-tracking parameters. Pulmonary artery catheter data were also measured. A classification and regression tree was made to identify prognostic models for the development of severe graft dysfunction.70 lung transplant recipients were included. Patients who developed severe primary graft dysfunction had better right ventricular function, as estimated by cardiac index (3.5±0.8 versus 2.6±0.7 L·min-1·m-2, p<0.01) and basal longitudinal strain (-25.7±7.3% versus -19.5±6.6%, p<0.01). Regression tree analysis provided an algorithm based on the combined use of three variables (basal longitudinal strain, pulmonary fibrosis disease and ischaemia time), allowing accurate preoperative discrimination of three distinct subgroups with low (11-20%), intermediate (54%) and high (75%) risk of severe primary graft dysfunction (area under the receiver operating characteristic curve 0.81).Better right ventricular function is a risk factor for the development of severe primary graft dysfunction. Preoperative estimation of right ventricular function could allow early identification of recipients at increased risk, who would benefit the most from careful perioperative management in order to limit pulmonary overflow.
Hypofractionated robotic radiosurgery for the treatment of clinically localized prostate cancer: Early biochemical results and acute toxicity.
Authors: E. Oermann, H. S. Hanscom, S. Lei, S. Suy, V. Chen, B. T. Collins, A. Dritschilo, J. H. Lynch, N. A. Dawson, S. P. Collins
Journal: Journal of Clinical Oncology (2010)

e15134 Background: Clinical data suggest that fewer large fractions are radio-biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is the ideal delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife system to deliver hypofractionated radiotherapy to localized prostate cancer. Methods: Thirty nine patients were treated with hypofractionated robotic radiosurgery with or without supplemental external radiation therapy and/or androgen deprivation therapy (26%). Four gold fiducials were placed within the prostate for X-ray guided prostate localization and beam adjustment. Fused CT and MRI scans were used for treatment planning. Sixteen patients were treated with radiosurgery alone (3625 cGy in five fractions). Twenty three patients were treated with radiosurgery (1950 cGy in three fractions) followed by IMRT (5040 cGy in 28 fractions). Quality of life data, including EPIC and IPSS questionnaires, was collected before and after treatment. The early PSA responses and acute urinary and rectal toxicities are reported here. Results: All 39 patients completed the proposed course of treatment without unplanned breaks. The mean pretreatment PSA was 9.63 ng/ml. PSA levels steadily decreased in all patients. The mean 6 month post-treatment PSA was 1.24 ng/ml. Acute side effects associated with treatment included grade 2 urinary and gastrointestinal toxicity. No patient experienced acute grade 3 or greater toxicity. IPSS scores returned to baseline by six months after treatment. Conclusions: Hypofractionated robotic radiosurgery using the CyberKnife system appears to be a well tolerated treatment alternative for older men with clinically localized prostate cancer. Early PSA results suggest an encouraging biochemical response. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Accuray, Inc. Accuray, Inc. Accuray, Inc.
Polymer brain-nanotherapeutics for multipronged inhibition of microglial α-synuclein aggregation, activation, and neurotoxicity
Authors: Neal K. Bennett, Rebecca Chmielowski, Dalia S. Abdelhamid, Jonathan J. Faig, Nicola Francis, Jean Baum, Zhiping P. Pang, Kathryn E. Uhrich, Prabhas V. Moghe
Journal: Biomaterials (2016)
Patient‐reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis
Authors: Sherean Farvardin, Jaimin Patel, Maleka Khambaty, Olutola A. Yerokun, Huram Mok, Jasmin A. Tiro, Adam C. Yopp, Neehar D. Parikh, Jorge A. Marrero, Amit G. Singal
Journal: Hepatology (2016)

Over 20% of patients with cirrhosis are nonadherent with hepatocellular carcinoma (HCC) surveillance recommendations; however, few studies have evaluated the impact of patient‐level factors on surveillance receipt. We characterized the association between HCC surveillance receipt and patient knowledge, attitudes, and perceived barriers in a racially diverse and socioeconomically disadvantaged cohort of patients with cirrhosis. Patients with cirrhosis followed at a large urban hospital were invited to complete a survey about HCC surveillance between August 2014 and December 2015. Multivariable logistic regression was performed to identify factors associated with HCC surveillance receipt during the 12‐month period preceding and 6‐month period after survey administration. We achieved a response rate of 71.8% (n = 541 of 753). Patients demonstrated high levels of HCC‐related knowledge (summary score, 77.7%); however, 48.6% believed that eating a healthy diet precluded the need for HCC surveillance, and 34.0% believed that HCC surveillance was not necessary if they had a normal physical exam and/or lacked clinical symptoms. Patients expressed worry about developing and dying from HCC, but nearly half (49.9%) of patients reported barriers to receiving HCC surveillance, including difficulty with the scheduling process (30.5%), costs of surveillance testing (25.3%), and transportation difficulties (17.3%). HCC surveillance receipt was significantly higher in patients who knew cirrhosis is a risk factor for developing HCC (odds ratio [OR], 3.09; 95% confidence interval [CI], 1.25‐7.62) and significantly lower in those reporting barriers to surveillance (OR, 0.42; 95% CI, 0.25‐0.70). Conclusion: Patients with cirrhosis are knowledgeable and interested in HCC surveillance; however, patient‐reported barriers are associated with lower surveillance rates in clinical practice and represent potential intervention targets to improve HCC surveillance effectiveness. (H epatology 2017;65:875‐884).
Temsirolimus in heavily pretreated patients with metastatic renal cell carcinoma: Preliminary results from the Austrian Compassionate Use Program
Authors: M. Schmidinger, U. M. Vogl, W. Lamm, M. Bojic, A. Bojic, C. C. Zielinski
Journal: Journal of Clinical Oncology (2008)

16125 Background: First-line treatment with the mTOR inhibitor Temsirolimus was shown to improve progression free survival and survival in patients with metastatic renal cell carcinoma and poor MSKCC risk profile. The role of Temsirolimus in patients being heavily pretreated with cytokines and targeted agents is unclear. The aim of this analysis was to investigate the impact of Temsirolimus in patients who had progressed under various types of therapies. Methods: From April to November 2007, all patients who had progressed under targeted agents were offered treatment with Temsirolimus at a dose of 25mg. White blood cell count and chemistry were obtained weekly, a detailed physical examination was performed every 2 weeks and tumor response was assessed every 8 weeks. Results: Starting in April 2007, 15 patients (male n=10, female n=5) with a median age of 71 years (range 44–80) were treated with Temsirolimus. All patients had a Karnofsky performance status of >70 and most were categorized with favorable (53.3%) or intermediate (40%) risk according to the MSKCC criteria. Sixty percent had 3 or more metastatic sites, including controlled brain metastases. Temsirolimus was median the 4th (range 2–5) systemic treatment offered to these patients since diagnosis of metastatic disease. Previous treatment consisted of cytokines (80%), sunitinib (80%), sorafenib (73.3%), bevacizumab (40%) or gemcitabine (40%). Grade 3 toxicities were rare and consisted of neutropenia, hypercholesterolemia and hyperglycemia (all 6.7%). Two patients (20%) experienced objective remission and 7 (70%) achieved stable disease. Progression free survival was median 19 weeks (median 1.3–37.1). Conclusions: With a clinical benefit response in 90% of the patients Temsirolimus seems to provide substantial benefits even in heavily pretreated patients. Grade 3 toxicities were rare and manageable. Extended data from a larger patient population will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Wyeth Wyeth
Tamoxifen benefits women who have had invasive breast cancer, community study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Women with invasive breast cancer should be encouraged to complete the full course of oestrogen blocking drugs to lower the risk of developing cancer in the other breast, researchers have said.

Their retrospective cohort study, published in JAMA Oncology , showed that treating women with invasive breast cancer with tamoxifen or aromatase inhibitors could lower the risk of contralateral breast cancer, especially among women whose breast cancer was oestrogen receptor positive.1

The study, which was the first to be carried out in a general community …
Association of Stimulant Medication Use With Bone Mass in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
Authors: Alexis J. Feuer, Ashley Thai, Ryan T. Demmer, Maria Vogiatzi
Journal: JAMA Pediatrics (2016)

Murine studies reveal that sympathetic nervous system activation leads to decreased bone mass. Stimulant medications used to treat attention-deficit/hyperactivity disorder (ADHD) increase sympathetic tone and may affect bone remodeling. Because bone mass accrual is completed by young adulthood, assessing stimulant effects on bone density in growing children is of critical importance.To investigate associations between stimulant use and bone mass in children and adolescents.This cross-sectional analysis used data collected from January 1, 2005, to December 31, 2010, from the National Health and Nutrition Examination Survey (NHANES) database. NHANES is a series of cross-sectional, nationally representative health and nutrition surveys of the US population. All children, adolescents, and young adults aged 8 to 20 years with dual-energy x-ray absorptiometry (DXA), anthropometric, demographic, and prescription medication use data were eligible for participation. Of the 6489 respondents included in the multivariable linear regression analysis, 159 were stimulant users and 6330 were nonusers. Data were analyzed from October 8, 2015, to December 31, 2016.Stimulant use, determined by questionnaires administered via interview.The association between stimulant use and total femur, femoral neck, and lumbar spine bone mineral content (BMC) and bone mineral density (BMD) was assessed using DXA.Study participants included 6489 NHANES participants with a mean (SD) age of 13.6 (3.6) years. Stimulant use was associated with lower bone mass after adjustment for covariates. Mean lumbar spine BMC was significantly lower in stimulant users vs nonusers (12.76 g; 95% CI, 12.28-13.27 g vs 13.38 g; 95% CI, 13.26-13.51 g; P = .02), as was mean lumbar spine BMD (0.90 g/cm2; 95% CI, 0.87-0.94 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .03) and mean femoral neck BMC (4.34 g; 95% CI, 4.13-4.57 g vs 4.59 g; 95% CI, 4.56-4.62 g; P = .03). Mean BMD of the femoral neck (0.88 g/cm2; 95% CI, 0.84-0.91 g/cm2 vs 0.91 g/cm2; 95% CI, 0.90-0.91 g/cm2; P = .08) and total femur (0.94 g/cm2; 95% CI, 0.90-0.99 g/cm2 vs 0.99 g/cm2; 95% CI, 0.98-0.99 g/cm2; P = .05) were also lower in stimulant users vs nonusers. Participants treated with stimulants for 3 months or longer had significantly lower lumbar spine BMD (0.89 g/cm2; 95% CI, 0.85-0.93 g/cm2 vs 0.94 g/cm2; 95% CI, 0.94-0.94 g/cm2; P = .02) and BMC (12.71 g; 95% CI, 12.14-13.32 g vs 13.38 g; 95% CI, 13.25-13.51 g; P = .03) and femoral neck BMD (0.87 g/cm2; 95% CI, 0.74-0.83 g/cm2 vs 0.91 g/cm2; 95% CI, 0.83-0.84 g/cm2; P = .048) than nonusers.Children and adolescents reporting stimulant use had lower DXA measurements of the lumbar spine and femur compared with nonusers. These findings support the need for future prospective studies to examine the effects of stimulant use on bone mass in children.
Complement pathway amplifies caspase-11–dependent cell death and endotoxin-induced sepsis severity
Authors: Brooke A. Napier, Sky W. Brubaker, Timothy E. Sweeney, Patrick Monette, Greggory H. Rothmeier, Nina A. Gertsvolf, Andreas Puschnik, Jan E. Carette, Purvesh Khatri, Denise M. Monack
Journal: The Journal of Experimental Medicine (2016)

Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11–dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9–mediated genome-wide screen, we identified novel mediators of caspase-11–dependent cell death. We found a complement-related peptidase, carboxypeptidase B1 (Cpb1), to be required for caspase-11 gene expression and subsequent caspase-11–dependent cell death. Cpb1 modifies a cleavage product of C3, which binds to and activates C3aR, and then modulates innate immune signaling. We find the Cpb1–C3–C3aR pathway induces caspase-11 expression through amplification of MAPK activity downstream of TLR4 and Ifnar activation, and mediates severity of LPS-induced sepsis (endotoxemia) and disease outcome in mice. We show C3aR is required for up-regulation of caspase-11 orthologues, caspase-4 and -5, in primary human macrophages during inflammation and that c3aR1 and caspase-5 transcripts are highly expressed in patients with severe sepsis; thus, suggesting that these pathways are important in human sepsis. Our results highlight a novel role for complement and the Cpb1–C3–C3aR pathway in proinflammatory signaling, caspase-11 cell death, and sepsis severity.
A phase I study of SAR566658, an anti CA6-antibody drug conjugate (ADC), in patients (Pts) with CA6-positive advanced solid tumors (STs)(NCT01156870).
Authors: Carlos Alberto Gomez-Roca, Valentina Boni, Victor Moreno, John Charles Morris, Jean-Pierre Delord, Emiliano Calvo, Kyriakos P. Papadopoulos, Olivier Rixe, Patrick Cohen, Alexia Tellier, Samira Ziti-Ljajic, Anthony W. Tolcher
Journal: Journal of Clinical Oncology (2016)

2511 Background: SAR566658 (SAR) is a maytansinoid-loaded ADC targeting CA6, a sialoglycotope of MUC-1 over-expressed in solid tumors and rarely in normal tissues. Methods: Phase I dose escalation and expansion study to evaluate SAR intravenous administration as single agent every 3 weeks (q3w) and 2 weeks (q2w). Primary objective included dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended dose (RD). Secondary objectives were PK, PD and preliminary efficacy assessment (RECIST1.1). Results: One hundred and fourteen patients (Pts) with heavily pretreated solid tumors expressing CA6 in ≥ 30% tumor cells with an intensity 2/3+ by immunohistochemistry were enrolled. SAR was administered across 11 dose levels (DLs) (10 to 240 mg/m² q3w and 120 mg/m² q2w). DLTs [1 grade (Gr) 3 diarrhea and 2 Gr3 keratitis] were observed at 240 mg/m². Initial RD was 190 mg/m² however a high incidence of keratopathy was seen mainly at cycle 2. PK/safety simulation, preserving drug exposure and limiting keratopathy incidence, proposed two alternative schedules: 90 mg/m² D1,D8 q3w and 120 mg/m² q2w. Most common adverse event (AE) was reversible Gr2/3 keratopathy in 41/114 (36%) (Gr3 in 9 Pts). Among these 41 Pts, 15/23 (65%) received 190 mg/m², 12/33 (36%) 150 mg/m², 6/8 (75%) 240 mg/m², 6/17 (35%) 90 mg/m² D1,D8 and 2/16 (13%) 120 mg/m² q2w. Prophylaxis with vasoconstrictor and steroids eye drops implemented in 8 patients in alternative schedules prevented keratopathy. Other AEs were fatigue (32.6%), peripheral neuropathy (31.6%), GI disorders [(nausea (29%), abdominal pain (26%), diarrhea (25%)] and neutropenia (2.6%). Low grade liver and renal abnormalities were noted.Tumor regression was noted in about 60% Pts at 190 and 90 mg/m² D1,D8 and 35% Pts at 150 and 120 mg/m² q2w. One complete response (ovary), 8 partial responses (3 breast, 2 ovary, 1 NSCLC, 1 cervix and 1 bladder) and 39% stable disease were noted. Highest overall response rate (ORR) was observed in 2/15 at 90 mg/m² D1,D8 and 3/23 at 190 mg/m². Conclusions: SAR 90 mg/m² D1,D8 q3w provided a favorable safety profile and encouraging antitumor activity and is selected as the RD for further clinical development. Clinical trial information: NCT01156870.