tbuckley/cabot-search huggingface dataset:
Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer
Authors: Lone V. Schøler, Thomas Reinert, Mai-Britt W. Ørntoft, Christine G. Kassentoft, Sigrid S. Árnadóttir, Søren Vang, Iver Nordentoft, Michael Knudsen, Philippe Lamy, Ditte Andreasen, Frank V. Mortensen, Anders R. Knudsen, Katrine Stribolt, Kim Sivesgaard, Peter Mouritzen, Hans J. Nielsen, Søren Laurberg, Torben F. Ørntoft, Claus L. Andersen
Journal: Clinical Cancer Research (2017)

Abstract Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention. Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period. Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P &amp;lt; 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (κ = 0.41; Spearman ρ = 0.4). Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients. Clin Cancer Res; 23(18); 5437–45. ©2017 AACR.
Characteristics of disease activity able to identify risk categories and probability to respond to first-line endocrine therapy (ET) in HR+ve/HER2-ve metastatic breast cancer (MBC) patients (pts): Dream or reality? Evaluation of a composite risk score in a subgroup population of the GIM 13-AMBRA study.
Authors: Giorgio Mustacchi, Marina Elena Cazzaniga, Monica Giordano, Ornella Garrone, Alessandra Beano, Lucia Del Mastro, Lorenzo Livi, Laura Iezzi, Andrea Michelotti, Anna Turletti, Ferdinando Riccardi, Michele De Laurentiis, Paolo Marchetti, Laura Biganzoli, Filippo Montemurro, Emanuela Romagnoli, Sabino De Placido, Paolo Pronzato
Journal: Journal of Clinical Oncology (2017)

1049 Background: The appropriate choice of 1st-line therapy in HR+ve/HER2-ve MBC pts is becoming more complicated since the data of front-line Fulvestrant and CDK 4/6 Inhibitors have been released. In the absence of predictive biomarkers of tumor response, one possible option is the recently proposed “composite score” (Schmid, ESMO 2016), composed by visceral tumor burden (VTB) and Disease-Free-Interval (DFI) to identify risk categories and the probability of response to ET or chemotherapy (CHT). Aim of the present analysis is to describe the choices of 1 st -line treatment and the response rate, according to the mentioned score in a population of HR+/HER2-ve MBC. Methods: We used data of the HR+ve pts of the AMBRA study, a longitudinal cohort study, describing the choice of first and subsequent lines of treatment in HER2-ve MBC pts (SABCS 2016 P5-15-07 &amp; P5-14-09). Using median DFI and VTB three categories of risk have been identified: Low (DFI &gt; 24 months &amp; VTB-), Intermediate (DFI £ 24 months &amp; VTB- or DFI &gt; 24 months &amp; VTB+) and High (DFI £ 24 months &amp; VTB+). This analysis describes the choices of 1 st -line therapy and relative response rate according to these risk categories. Results: So far, 791/1500 pts have been registered into the AMBRA study, 673 of them (85%) with HR+ MBC and 659 (83.3%) are evaluable for this analysis. Risk categories and response to therapy are detailed in the table below. Conclusions: No conclusion can be done regarding the “High Risk” group because of the low number of pts treated with ET alone. Regarding the “Low” and “Intermediate” risk categories, we can conclude that the proposed “composite risk score” doesn’t seem to discriminate MBC patients who could be treated with ET alone or with a more aggressive treatment, at least in terms of response rate. [Table: see text]
Boosting the Peroxidase-Like Activity of Nanostructured Nickel by Inducing Its 3+ Oxidation State in LaNiO<sub>3</sub> Perovskite and Its Application for Biomedical Assays
Authors: Xiaoyu Wang, Wen Cao, Li Qin, Tingsheng Lin, Wei Chen, Shichao Lin, Jia Yao, Xiaozhi Zhao, Min Zhou, Cheng Hang, Hui Wei
Journal: Theranostics (2017)

Catalytic nanomaterials with intrinsic enzyme-like activities, called nanozymes, have recently attracted significant research interest due to their unique advantages relative to natural enzymes and conventional artificial enzymes.Among the nanozymes developed, particular interests have been devoted to nanozymes with peroxidase mimicking activities because of their promising applications in biosensing, bioimaging, biomedicine, etc. Till now, lots of functional nanomaterials have been used to mimic peroxidase.However, few studies have focused on the Ni-based nanomaterials for peroxidase mimics.In this work, we obtained the porous LaNiO3 nanocubes with high peroxidase-like activity by inducing its 3+ oxidation state in LaNiO3 perovskite and optimizing the morphology of LaNiO3 perovskite.The peroxidase mimicking activity of the porous LaNiO3 nanocubes with Ni 3+ was about 58~fold and 22~fold higher than that of NiO with Ni 2+ and Ni nanoparticles with Ni 0 .More, the porous LaNiO3 nanocubes exhibited about 2-fold higher activity when compared with LaNiO3 nanoparticles.Based on the superior peroxidase-like activity of porous LaNiO3 nanocubes, facile colorimetric assays for H2O2, glucose, and sarcosine detection were developed.Our present work not only demonstrates a useful strategy for modulating nanozymes' activities but also provides promising bioassays for clinical diagnostics.
Could This Be the Last Word on Hypertonic Saline?
Authors: Shawn L. Ralston
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Genome-wide association study to identify variants associated with acute severe vaso-occlusive pain in sickle cell anemia
Authors: Shruti Chaturvedi, Pallav Bhatnagar, Christopher J. Bean, Martin H. Steinberg, Jaqueline N. Milton, James F. Casella, Emily Barron-Casella, Dan E. Arking, Michael R. DeBaun
Journal: Blood (2017)
Abstract 176: Interleukin 17 A, Hepatosplenic Mansonic Schistosomiasis and Atherosclerosis
Authors: Dinaldo C Oliveira, Diego Santos, Thamires Alcantara, Ana L Coutinho, Carlos Brandt
Journal: Circulation Research (2015)

Introduction: The immune system plays an important role in the pathophysiology of schistosomiasis and atherosclerosis due to its activation of various immune cells and release of different inflammatory mediators. However, the pathologies of these diseases are not fully understood. The main aim of this study was to detect atherosclerotic disease in patients with mansonic schistosomiasis, while the secondary objectives were evaluate the serum concentrations of interleukin 17A (IL 17 A) and 22 (IL 22). Hypothesis: Atherosclerosis is not common in patients with mansonic schistosomiasis. Methods: This study included 30 patients (14 men, 16 women; mean age = 59.87 ± 7.50 years) with hepatosplenic mansonic schistosomiasis that agreed to participate in the study by signing the Free and Informed Consent Form. Ten healthy volunteers (four men, six women) were selected as controls for interleukin concentrations. Atherosclerosis was evaluated by measuring the carotid artery intima-media thickness (IMT ≥1.5 mm are indicative of atherosclerotic plaques). Shapiro-Wilk test was necessary to determine whether the variables followed a normal distribution. The continuous variables were evaluated using student’s t test. P value ≤ 0.05 was considered statistically significant. Results: The main clinical characteristics of the patients were as follows: benign arrhythmias, 19 patients (63%); hypertension, 17 (56%); smoking, 12 (40%); hepatitis B or C, nine (30%); peripheral vascular insufficiency, nine (30%); family history of CAD, nine (30%); diabetes mellitus, one (3.3%); leukemia, one (3.3%); and non-cardiac surgery, 24 (80%). There were no differences in the IL 17 A concentrations (15.63 ± 0.00 pg/ml vs 15.63 ± 0.00 pg/ml, p = 1) and in the IL 22 concentrations (7.81 ± 0.00 pg/ml vs 7. 81 ± 0.00 pg/ml, p = 1) between patients and controls. The overall mean of the intimal medial thickness was 0.7 ± 0.2 mm Conclusions: None of patients had atheroma. The serum concentrations of IL 17A and IL 22 were equal between patients and controls (concentrations undetectable or low). It is possible that the immune response of patients with hepatosplenic mansonic schistosomiasis may attenuate the development of atherosclerosis.
Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta‐analysis
Authors: Guangqin Xiao, Sixian Zhu, Xiao Xiao, Lunan Yan, Jiayin Yang, Gang Wu
Journal: Hepatology (2017)

Many noninvasive methods for diagnosing liver fibrosis (LF) have been proposed. To determine the best method for diagnosing LF in nonalcoholic fatty liver disease (NAFLD), we conducted a systemic review and meta-analysis to compare the performance of aspartate aminotransferase to platelets ratio index (APRI), fibrosis-4 index (FIB-4), BARD score, NAFLD fibrosis score (NFS), FibroScan, shear wave elastography (SWE), and magnetic resonance elastography (MRE) for diagnosing LF in NAFLD. We compared the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC) of these noninvasive methods for detecting significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis. Heterogeneity was explored using meta-regression. Sixty-four articles with a total of 13,046 NAFLD subjects were included. The overall mean prevalence of SF, AF, and cirrhosis was 45.0%, 24.0%, and 9.4% in NAFLD patients, respectively. With an APRI threshold of 1.0 and 1.5, the sensitivities and specificities were 50.0% and 84.0% and 18.3% and 96.1%, respectively, for AF. With a FIB-4 threshold of 2.67 and 3.25, the sensitivities and specificities were 26.6% and 96.5% and 31.8% and 96.0%, respectively, for AF. The summary sensitivities and specificities of BARD score (threshold of 2), NFS (threshold of -1.455), FibroScan M (threshold of 8.7-9), SWE, and MRE for detecting AF were 0.76 and 0.61, 0.72 and 0.70, 0.87 and 0.79, 0.90 and 0.93, and 0.84 and 0.90, respectively. The summary AUROC values using APRI, FIB-4, BARD score, NFS, FibroScan M probe, XL probe, SWE, and MRE for diagnosing AF were 0.77, 0.84, 0.76, 0.84, 0.88, 0.85, 0.95, and 0.96, respectively.MRE and SWE may have the highest diagnostic accuracy for staging fibrosis in NAFLD patients. Among the four noninvasive simple indexes, NFS and FIB-4 probably offer the best diagnostic performance for detecting AF. (Hepatology 2017;66:1486-1501).
RADICAL trial: A phase Ib/IIa study to assess the safety and efficacy of AZD4547 in combination with either anastrozole or letrozole in ER positive breast cancer patients progressing on these aromatase inhibitors (AIs).
Authors: Michael Seckl, Philip David Badman, Xinxue Liu, Iain R. MacPherson, Ishtiaq Husain Zubairi, Richard D. Baird, Javier Garcia-Corbacho, Nicola Cresti, Elizabeth R. Plummer, Anne Caroline Armstrong, Rozenn Allerton, Donal Landers, Hanna Nicholas, Lyndall McLellan, Adrian K. Lim, Charles Coombes
Journal: Journal of Clinical Oncology (2017)

1059 Background: Patients with metastatic ER positive breast cancer invariably experience disease progression whilst taking AIs. Fibroblast growth factor receptor inhibitors (FGFRI) such as AZD4547 can reverse endocrine resistance in breast cancer cells. Consequently, we designed the RADICAL trial to test the safety and efficacy of AZD4547 combined with letrozole (L) or anastrozole (A). Methods: Patients with prior disease progression on either AI were initially recruited to a Phase Ib study which showed that L 2.5mg or A 1mg daily continuously could be safely combined with AZD4547 80mg twice daily on a 1wk on/1 wk off schedule. Pharmacokinetic data showed no significant interactions. Subsequently, 52 patients progressing on these AIs were recruited, either continuing, or, if other therapies had subsequently been given, restarting their prior AI together with AZD4547. Primary endpoint was change in tumour size (RECIST v 1.1) at 12 weeks compared to baseline. Results: Enrolled patients had previously received a median of 4 (range: 1-11) systemic therapies, including endocrine treatments with a median of 2 (range: 1-6). The mean tumour size change at 12 and 28 weeks was 7% (95%CI: -4%, 17%) and 8% (95%CI: -4%, 20%), respectively. Clinical benefit assessed by partial response (PR) or stable disease (SD) occurred in 36.5% (1 PR and 18 SD) and 25% (2 PR and 11 SD) of patients at 12 and 28 weeks, respectively. The median progression free survival was 3.1 months (95%CI: 2.4-5.4). Most adverse events (AEs) were G1/2 (95.3%). 11 (21%) patients developed asymptomatic AZD4547-induced retinal pigment epithelial detachment, all resolved and 1 and 6 were able to continue on study medication at full and half dose, respectively. Among 34 G3/4 AEs, only 6 were probably/possibly related to AZD4547. Out of 13 unrelated serious AEs, 2 were fatal. Conclusions: Combined AZD4547 with L or A appears to be safe and shows anti-tumour activity in advanced ER+ patients resistant to these AIs. Development of a biomarker to select patients for this therapy will facilitate future studies. Clinical trial information: NCT01791985.
Postmastectomy radiation in women with node positive breast cancer in the Ontario population.
Authors: Steven Latosinsky, Krista Bray Jenkyn, Lihua Li, Salimah Shariff
Journal: Journal of Clinical Oncology (2017)

e12104 Background: Despite two randomized controlled trials first published in 1997 showing improvements in both locoregional control and survival, postmastectomy radiation for node positive breast cancer patients has not been universally accepted; particularly for patients with 1-3 positive nodes. Subsequent favorable meta-analyses have resulted in more recent guidelines supporting postmastectomy radiation. We examined the rate and predictors of postmastectomy radiation receipt in node positive breast cancer patients in Ontario (population 13.2 million). Methods: We used the Ontario Cancer Registry, a population-based, prospectively-collected registry, to identify all node positive female breast cancer patients in the province with a diagnosis date between April 1, 2010 and Sept 30, 2014. Patient records were linked to prospectively maintained health administrative databases. Through these databases, the universal single-payer health care system in Ontario can capture details for each patient for all health care encounters, hospitalizations, procedures (mastectomy), prescription medications, systemic cancer therapy and radiation. Logistic regression modeling using generalized estimating equations was employed to determine the association between patient, tumor and treatment characteristics and receipt of radiation, while accounting for the possible clustering effect by health regions. Results: Of the 6,535 women with node positive breast cancer who had undergone a mastectomy 73.9% received radiation. Of the 4227 women with 1-3 positive nodes, 68.7% received radiation, and of the 2308 women with &gt; 3 positive nodes 83.4% received radiation. Receipt of radiation was positively associated with younger age ( &lt; 70 years), increasing cancer stage and a lower Charlson comorbidity index. Conclusions: In a setting with universal healthcare, the majority of women with node positive breast cancer in Ontario received postmastectomy radiation, including women with 1-3 positive nodes. Older women, those with higher stage and those who had increased co-occurring medical conditions were less likely to receive radiation therapy.
Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC).
Authors: Sara M. Tolaney, William Thomas Barry, Hao Guo, Deborah Dillon, Chau T. Dang, Denise A. Yardley, Beverly Moy, P. Kelly Marcom, Kathy S. Albain, Hope S. Rugo, Matthew James Ellis, Iuliana Shapira, Antonio C. Wolff, Lisa A. Carey, Beth Overmoyer, Ann H. Partridge, Clifford A. Hudis, Ian E. Krop, Harold J. Burstein, Eric P. Winer
Journal: Journal of Clinical Oncology (2017)

511 Background: Retrospective data suggest that patients (pts) with small HER2+ cancers have more than just minimal risk of disease recurrence. The APT trial was designed to address treatment for such pts. We have previously reported 3-yr disease-free survival (DFS) and here we provide an updated analysis with 7-yr DFS. Methods: APT is a single arm multicenter, phase II study of TH. Pts with HER2+ BC (IHC 3+ and/or FISH ratio &gt; 2.0) with negative nodes (a single axillary lymph node micrometastasis was allowed) and tumor size &lt; 3 cm were eligible. Pts received T (80 mg/m 2 ) with H x 12 weekly (w), followed by H (weekly or q3w) x 39w. The primary endpoint was DFS. Recurrence Free Interval (RFI), Breast Cancer Specific Survival (BCSS), and overall survival (OS) were also analyzed. Intrinsic subtyping by PAM50 was performed on the nCounter Analysis system on archival tissue. Results: 410 pts were enrolled from September 2007 to September 2010 and 406 began protocol therapy. 67% had hormone-receptor (HR)+ tumors. Distribution by tumor size: 2% T1mi; 17% T1a; 30% T1b; 42% T1c, and 9% T2 ≤ 3 cm. 6 pts had a nodal micrometastasis. With a median follow-up of 6.5 yrs, there were 23 DFS events observed: 4 (1.0%) distant recurrences, 5 local/regional recurrences (1.2%), 6 new contralateral BC (1.5%), and 8 deaths without documented recurrence (2.0%). The 7-yr DFS was 93.3% (95% CI 90.4-96.2); 7-yr DFS for HR+ pts was 94.6% (95% CI 91.8-97.5) and for HR- pts was 90.7% (95% CI 84.6-97.2). 7-yr RFI was 97.5% (95% CI 95.9-99.1); 7-year BCSS is 98.6% (95% CI 97.0-100); and 7-yr OS was 95.0% (95% CI 92.4-97.7). Ongoing PAM50 testing (n = 227 pts) identified 142 (63%) HER2-enriched; 22 (10%) luminal A, 26 (11%) luminal B, and 20 (9%) basal-like; 17 samples had a poor quality assay. Additional testing and associations with clinical outcomes will be presented at the meeting. Conclusions: These data suggest that TH as adjuvant therapy for node-negative HER2+ BC is associated with few recurrences and only 4 distant recurrences with longer follow-up. Based on these data, if chemotherapy/trastuzumab is given to a pt with stage I HER2+ breast cancer, the TH regimen should be considered a standard treatment. Clinical trial information: NCT00542451.
Abstract 162: Influence of Age and Ischemia on Cardiac Subsarcolemmal and Interfibrillar Mitochondria in a Novel Model of Estrogen Deficiency
Authors: Alexandra M Garvin, Nicole C Aurigemma, Donna H Korzick
Journal: Circulation Research (2015)

Altered mitochondrial respiration (MR) and calcium retention capacity (CRC) are proposed cardiac cell death mechanisms exacerbated by aging in males. The present study aimed, for the first time, to determine changes in mitochondrial subpopulation function with age and ischemia/reperfusion (I/R) injury in the female heart. A novel model to recapitulate human menopause/age interactions was used in F344 female rats ovariectomized (OVX) at 15mo and studied at 24mo (MO OVX; n=15), vs adult (6mo; n=18). MR and CRC were assessed in isolated subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria following in vivo coronary artery ligation (CAL; 31 min I and 10 min R) or sham. State 3 MR energized by either complex I (CI) or complex II (CII) substrates was selectively reduced by age in SSM (p&lt;.02), and by I/R in IFM (p&lt;.05). The I/R-dependent decrease in CRC was 64% (18 vs 29.5) greater in MO OVX vs. adult IFM, suggesting earlier mitochondrial permeability transition pore (MPTP) opening. At CI, but not CII, cyclosporine A (CsA) enhanced CRC 20% (103 vs 86) more in SSM and 75% (98 vs 56) more in IFM from adult compared to MO OVX, suggesting reduced protective efficacy with age and MPTP involvement. Additionally, mitochondrial cyclophilin D increases with age, while cytoplasmic RIP1 is increased with age and I/R further implicating the MPTP mechanism and link with programmed necrosis in the aged female heart. In contrast to males, our data suggest a sex-specific phenotype whereby reductions in both SSM and IFM dynamics may play an additive role in the enhanced susceptibility to I/R injury and myocardial infarction in the aged female heart, which remains the leading cause of death in older women.