tbuckley/cabot-search huggingface dataset:
Prognostic role of serum vascular endothelial growth factor level in hepatocellular carcinoma.
Authors: A. Tan, F. Aucejo, X. Liu, R. Lopez, R. D. Kim
Journal: Journal of Clinical Oncology (2010)

e14662 Background: The only curative option for unresectable hepatocellular carcinoma (HCC) is liver transplantation. Pathologic characteristics at the time of surgery such as vascular invasion is known to predict an increased risk of recurrence after transplantation. HCC, a highly vascular tumor, expresses vascular endothelial growth factor (VEGF). A high serum VEGF level has been shown to correlate with tumor progression and metastasis in several human cancers but its significance in HCC is unclear. This pilot, prospective study aims to correlate the expression of preoperative serum VEGF levels with pathologic features of HCCs in liver transplantation settings. Methods: 48 consecutive HCC patients who underwent a liver transplantation from 01/2008 to 04/2009 at the Cleveland Clinic Foundation were identified. Preoperative serum VEGF levels were measured in 27 patients using enzyme-linked immunosorbent assay (ELISA) and correlated with pathologic findings at the time of surgery. Results: Using Receiver Operating Characteristics (ROC) analysis, preoperative serum VEGF >31 pg/ml appeared to correlate with the presence vascular invasion, poor differentiation and/or features beyond the Milan criteria. Patients with a preoperative serum VEGF level >31 pg/ml were 5.2 times more likely to have any or all of these poor pathologic features compared to those with lower levels. This however did not reach statistical significance (p=0.061). Conclusions: There is a trend suggesting that a higher serum VEGF level is predictive of poor pathologic features at the time of liver transplantation for HCC. Large studies with long term follow-up are needed to evaluate its role in HCC patients in liver transplantation settings. Patient characteristics Factor All (N=27) Pretransplant treatment 16 (59.3) Positive margin 0 (0.0) Vascular invasion 12 (44.4) Within Milan 15 (55.6) Grade (N=24) Well 3 (12.5) Moderate 15 (62.5) Poor 6 (25.0) Vascular invasion, beyond Milan and/or poor differentiation 18 (66.7) # lesions on explant path 1 12 (44.4) 2 5 (18.5) 3 4 (14.8) 4 3 (11.1) 5 3 (11.1) Largest lesion on explant path (cm) 3.5 (1.7) % necrosis on explanted HCCs (N=24) 0.4 (0.3) Mean (SD) for lesion size and % necrosis. Otherwise, N (%). No significant financial relationships to disclose.
Upper airway and systemic inflammation in obstructive sleep apnoea
Authors: Eugenio Vicente, Jose M. Marin, Santiago J. Carrizo, Carlos S. Osuna, Ricardo González, Marta Marin-Oto, Marta Forner, Paul Vicente, Pablo Cubero, Ana V. Gil, Xavier Soler
Journal: European Respiratory Journal (2016)

Obstructive sleep apnoea (OSA) is associated with pharyngeal inflammation, but the coexistence of systemic inflammation is controversial. This study investigated whether local and systemic inflammatory biomarkers are related in patients with OSA. An uncontrolled extension to the study assessed the response to effective treatment. We recruited 89 patients with OSA (apnoea/hypopnoea index (AHI) ≥5 events·h −1 ), 28 snorers and 26 healthy controls. Pharyngeal lavage (PHAL) and plasma samples were collected at baseline and after a 1-year follow-up. Inflammatory cells were evaluated by flow cytometry; interleukin (IL)-6, IL-8 and tumour necrosis factor-α were evaluated by immunoassay. In PHAL, CD4 + T-cells, IL-6 and IL-8 were higher in OSA patients than in snorers or healthy controls (p&lt;0.05). The AHI correlated with CD4 + , IL-6 and IL-8 in PHAL (all p-values &lt;0.05). There were no differences in the inflammatory biomarkers in plasma between the study groups and no relationship between plasma and PHAL biomarkers. Biomarkers decreased significantly in PHAL but not in plasma after 1 year of therapy with continuous positive airway pressure or surgery. In patients with OSA, increased levels of inflammatory biomarkers were found in PHAL, which were reduced with effective treatment. No simultaneous increase in plasma inflammatory biomarkers was found.
Comprehensive mutation analysis in NRG Oncology/RTOG 9802: A phase III study of RT vs RT + PCV in high-risk low-grade gliomas (LGGs).
Authors: Erica Hlavin Bell, Joseph P McElroy, Jessica Fleming, Cynthia Dawn Timmers, Arup R Chakraborty, Andrea L Salavaggione, Edward G. Shaw, Kenneth D. Aldape, David Brachman, Albert D Murtha, Minhee Won, Minesh P. Mehta, Arnab Chakravarti
Journal: Journal of Clinical Oncology (2016)

2017 Background: This study sought to examine the prognostic significance of mutations within IDH1/2, ATRX, CIC, FUBP1, and the TERT promoter in a prospective phase III study of high-risk LGG using multivariate analyses (MVAs). Methods: IDH mutation status was determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq DNA panel was used for mutation analysis; TERT promoter mutations were detected by Sanger sequencing. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated and tested using the Cox proportional hazard model and the log-rank test. MVAs were performed incorporating age, treatment, surgery, histology, and performance status as covariates. Results: Observed mutations, by frequencywere 74% (85/115) within IDH1/2, TERT promoter in 40% (32/80), CIC in 25% (17/69), ATRX in 24% (16/67), and FUBP1 in 10% (7/69). In the univariate analysis (UVA) on OS, IDH1/2 (HR = 0.40; p < 0.001), CIC (HR = 0.40; p = 0.04), and TERT promoter mutations (HR = 0.40; p = 0.007) were all statistically significant. For PFS, by UVA, IDH1/2 mutations (HR = 0.45; p = 0.003) were significantly associated with better outcome, and TERT promoter (HR = 0.62; p = 0.11) and CIC mutations (HR = 0.56; p = 0.12) trended toward better PFS. Upon MVA, TERT promoter (HR = 0.41; p = 0.04) and CIC mutations (HR = 0.23; p = 0.01) were significantly associated with OS, whereas IDH1/2 mutations were significantly associated with PFS (HR = 0.46; p = 0.005). Conclusions: This study underscores the prognostic value of TERT promoter, IDH, and CIC mutations and suggests that TERT and CIC may provide additional information beyond IDH. Most importantly, this is the first study to examine the prognostic effects of these mutations using rigorous MVA in a grade II cohort with prospectively-collected, well-annotated clinical data. Efforts to increase sample size and to perform predictive analyses are ongoing. Funding: U10CA21661, U10CA180868, U10CA180822, and U10CA37422 (NCI). Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC). Clinical trial information: NCT00003375.
Ferritin Heavy Chain Stimulates HbS-to-HbF Switching in Erythroid Precursor Cells from Sickle Cell Patients.
Authors: Robert H. Broyles, Visar Belegu, Austin C. Roth, Emily J. Clarkson, Kelly S. Williamson, Charles A. Stewart, Quentin N. Pye, Robert A. Floyd, Klodiana Jani, Marie Trudel, Paolo Santambrogio, Sonia Levi, Paolo Arosio, Joan Parkhurst Cain
Journal: Blood (2006)
No Association of Lower Hippocampal Volume With Alzheimer’s Disease Pathology in Late-Life Depression
Authors: François-Laurent De Winter, Louise Emsell, Filip Bouckaert, Lene Claes, Saurabh Jain, Gill Farrar, Thibo Billiet, Stephan Evers, Jan Van den Stock, Pascal Sienaert, Jasmien Obbels, Stefan Sunaert, Katarzyna Adamczuk, Rik Vandenberghe, Koen Van Laere, Mathieu Vandenbulcke
Journal: American Journal of Psychiatry (2016)

Hippocampal volume is commonly decreased in late-life depression. According to the depression-as-late-life-neuropsychiatric-disorder model, lower hippocampal volume in late-life depression is associated with neurodegenerative changes. The purpose of this prospective study was to examine whether lower hippocampal volume in late-life depression is associated with Alzheimer's disease pathology.Of 108 subjects who participated, complete, good-quality data sets were available for 100: 48 currently depressed older adults and 52 age- and gender-matched healthy comparison subjects who underwent structural MRI, [18F]flutemetamol amyloid positron emission tomography imaging, apolipoprotein E genotyping, and neuropsychological assessment. Hippocampal volumes were defined manually and normalized for total intracranial volume. Amyloid binding was quantified using the standardized uptake value ratio in one cortical composite volume of interest. The authors investigated group differences in hippocampal volume (both including and excluding amyloid-positive participants), group differences in amyloid uptake and in the proportion of positive amyloid scans, and the association between hippocampal volume and cortical amyloid uptake.A significant difference was observed in mean normalized total hippocampal volume between patients and comparison subjects, but there were no group differences in cortical amyloid uptake or proportion of amyloid-positive subjects. The difference in hippocampal volume remained significant after the amyloid-positive subjects were excluded. There was no association between hippocampal volume and amyloid uptake in either patients or comparison subjects.Lower hippocampal volume was not related to amyloid pathology in this sample of patients with late-life depression. These data counter the common belief that changes in hippocampal volume in late-life depression are due to prodromal Alzheimer's disease.
Are There Still Too Few Suicides to Generate Public Outrage?
Authors: Megan C. Lytle, Vincent M. B. Silenzio, Eric D. Caine
Journal: JAMA Psychiatry (2016)

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 Psychiatry 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 Psychiatry journal
Phase I trial of pemetrexed, carboplatin, and sorafenib as first-line treatment in patients with metastatic NSCLC.
Authors: C. H. Brandts, B. Borchard, C. F. Waller, U. M. Martens, M. Mohr, C. Young, J. Gerss, H. Serve, W. E. Berdel, R. Wiewrodt
Journal: Journal of Clinical Oncology (2010)

e18112 Background: Lung cancer is the leading cause of cancer death worldwide and the majority of patients present with locally advanced or metastatic disease. Novel treatment regimens combining multikinase inhibitors with platinum-based chemotherapy may increase efficacy without additional toxicity. Methods: 12 patients (median age 62 yrs (44-77); 4/12 females; 7/12 ECOG 0) with untreated NSCLC (UICC6 stage IIIB with pleural effusion and IV; 7/12 non-squamous cell histology) were enrolled in a phase I dose escalation trial and received sorafenib 200mg bid (n = 3) to 400 mg bid (n = 9) d2-d19 following pemetrexed 500 mg/m2 d1 and carboplatin AUC6 d1. The primary endpoint was to determine the recommended sorafenib dose, secondary endpoints were safety, toxicity and efficacy. Results: 52treatment cycles were applied. 11/12 patients experienced CTCAE grade 3/4 hematotoxicity (83% thrombocytopenia, 83% neutropenia, 92% leucopenia) requiring one (n = 2) or two dose reductions (n = 7). The majority of dose reductions were caused by grade 3/4 thrombocytopenia (82%). 4/7 patients were withdrawn from the trial after experiencing grade 3/4 thrombocytopenia in three consecutive cycles despite two dose reductions. Other grade 3/4 adverse events were infrequent (25%). Best responses were PR in 3 patients (25%), SD in 8 patients (67%), and PD in 1 patient (8%). Median PFS was 6.3 months (95%CI 3.7-8.9) and median OS was 14.7 months (6.8-22.6). Results do not differ among the sorafenib dose cohorts (200 mg bid vs. 400 mg bid) and among histology (squamous vs. non-squamous NSCLC) (p > 0.1, all comparisons). Conclusions: Both in squamous and non-squamous metastatic NSCLC, the combination of sorafenib with pemetrexed-carboplatin was active and safe except for hematotoxicity. Sorafenib administered in this combination appears to enhance thrombocytopenia compared to historical data. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Advisory Board Member
Face transplant: long-term follow-up and results of a prospective open study
Authors: Laurent Lantieri, Philippe Grimbert, Nicolas Ortonne, Caroline Suberbielle, Dominique Bories, Salvador Gil-Vernet, Cédric Lemogne, Frank Bellivier, Jean Pascal Lefaucheur, Nathaniel Schaffer, Fréderic Martin, Jean Paul Meningaud, Pierre Wolkenstein, Mikael Hivelin
Journal: The Lancet (2016)
Demographics and Long-Term Outcome of Incident Immune Thrombocytopenic Purpura: A Twelve-Years Nationwide Population-Based Study in Taiwan
Authors: Bor-Sheng Ko, Grace Hui-Min Wu, Yu-Chiao Wang, Ming Yao, Churn-Shiouh Gau, Szu-Chun Hsu, Jih-Luh Tang, Raoh-Fang Pwu
Journal: Blood (2015)
Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction
Authors: James T. Thackeray, Jens P. Bankstahl, Yong Wang, Kai C. Wollert, Frank M. Bengel
Journal: Theranostics (2016)

Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies.Molecular imaging holds promise for guidance of such therapies.The amino acid 11 C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes.We assessed the suitability of positron emission tomography (PET) with 11 C-methionine for imaging post-MI inflammation, from cell to mouse to man.Uptake assays demonstrated 7-fold higher 11 C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001).C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery.Serial 11 C-methionine PET was performed 3, 5 and 7d later.MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV).PET detected increased 11 C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/gvs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy).Increased 11 C-methionine uptake was associated with macrophage infiltration of damaged myocardium.Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and 11 C-methionine uptake by 46% at 3d post-MI.A patient study at 3d after ST-elevation MI and early reperfusion confirmed elevated 11 C-methionine uptake in the hypoperfused myocardial region.Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. 11 C-methionine-based molecular imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies.
Discordant Aortic Valve Morphology in Monozygotic Twins
Authors: Dawn S. Hui, Robert O. Bonow, Joshua M. Stolker, Stephen R. Braddock, Richard Lee
Journal: JAMA Cardiology (2016)

Bicuspid aortic valve (BAV) is considered an autosomal dominant condition, which is commonly associated with thoracic aortic aneurysm. Both conditions pose the risk of valvular and aortic complications not only for affected patients but also for genetically related persons as well. The genetic underpinnings of these disease processes, which are in various stages of elucidation, have implications for screening and risk prognostication.To analyze genetic differences between 2 pairs of monozygotic twins that had discordant aortic valve morphology, with 1 twin in each pair having a BAV and the other having a trileaflet aortic valve.Two pairs of twins that were objectively determined to be monozygotic were examined at a tertiary care medical center associated with an academic medical center. Aortic valves that were surgically excised for clinical indications were examined for morphology. Whole-exome sequencing was performed for the twin pair that had discordance of aortic valve and aortic aneurysm. In the second pair, targeted gene sequencing of 25 genes known to be associated with BAV and/or thoracic aortic aneurysm was performed. In each pair, the twin with a BAV underwent surgical aortic valve replacement for clinical indications.Genetic coding variations between monozygotic twins using whole-exome sequencing and targeted gene sequencing.This case series included 2 pairs of male monozygotic twins; one pair was aged 51 years and the other aged 59 years. Genetic sequencing methods identified no pathogenic sequence changes between the twins in each pair.Our findings challenge the traditional view of BAV as a condition with an entirely autosomal dominant inheritance pattern and emphasize the variability of penetrance of both BAV and thoracic aortic aneurysm as well as the variability of the association of the 2 conditions. Continued work to elucidate the genetic basis may lead to the refinement of risk stratification for affected patients and relatives.
Prognostic Importance of Comorbidity in a Population-Based Analysis of Patients with Advanced-Stage Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP
Authors: André Wieringa, Eric N. van Roon, Peter Joosten, Tim Beerden, Huib Storm, Robby Kibbelaar, Hanneke C. Kluin-Nelemans, Nic J.G.M. Veeger, Mels Hoogendoorn
Journal: Blood (2012)
Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers
Authors: Zhenghe Wang, Li Li, Kishore Guda, Zhengyi Chen, Jill Barnholtz-Sloan, Young Soo Park, Sanford D. Markowitz, Joseph Willis
Journal: JNCI Journal of the National Cancer Institute (2016)

African Americans have the highest incidence and mortality from colorectal cancer (CRC) of any US racial group. We recently described a panel of 15 genes that are statistically significantly more likely to be mutated in CRCs from African Americans than in Caucasians (AA-CRC genes). The current study investigated the outcomes associated with these mutations in African American CRCs (AA-CRCs). In a cohort of 66 patients with stage I-III CRCs, eight of 27 CRCs with AA-CRC gene mutations (Mut+) developed metastatic disease vs only four of 39 mutation-negative (Mut-) cases (P = .03, Cox regression model with two-sided Wald test). Moreover, among stage III cases (n = 33), Mut+ cancers were nearly three times more likely to relapse as Mut- cases (7 of 15 Mut+ vs 3 of 18 Mut-; P = .03, Cox regression model with two-sided Wald test). AA-CRC mutations may thus define a high-risk subset of CRCs that contributes to the overall disparity in CRC outcomes observed in African Americans.
Donor Natural Killer (NK) Alloreactivity Predicts Long-Term Relapse-Free Survival in Acute Myeloid Leukemia Patients Undergoing Immunotherapy with NK Cells
Authors: Antonio Curti, Loredana Ruggeri, Sarah Parisi, Andrea Bontadini, Elisa Dan, Simonetta Rizzi, Maria Rosa Motta, Sara Trabanelli, Darina Ocadlikova, Mariangela Lecciso, Valeria Giudice, Elena Urbani, Cristina Papayannidis, Giovanni Martinelli, Francesca Bonifazi, Giuseppe Bandini, Fiorenza Fruet, Russel E. Lewis, Michele Cavo, Andrea Velardi, Roberto M. Lemoli
Journal: Blood (2014)
Abstract 11616: Effect of a Lifestyle Weight Loss Intervention on Visceral Fat and Glycemic Control Among Individuals With and Without Type 2 Diabetes
Authors: Soohyun Nam, Soohyun Nam, Devon A Dobrosielski, Kerry J Stewart
Journal: Circulation (2015)

Background: Though a high amount of visceral fat is associated with insulin resistance, which can lead to type 2 diabetes (T2D) and cardiovascular diseases (CVDs), less is known about whether lifestyle modification (weight loss diet and exercise) induced changes in visceral fat are associated with improvements in glycemia. Methods: We randomized 77 individuals aged 35-65 years with T2D or pre-diabetes to 6-months of weight loss diet (D); or D combined with supervised moderate-intensity exercise training (D+E). Study measures were total abdominal, visceral and subcutaneous fat volumes by magnetic resonance imaging, aerobic fitness expressed as VO 2 peak during treadmill testing, body mass index (BMI), and HbA1c levels from blood samples. Results: Of 77 subjects (mean age, 54.8±7.8 years; mean BMI, 34.5 ± 4.7 kg/m 2 , women, 77.9%; Whites-65%, Blacks-34%, Asians-1%), n=37 had T2D and n=40 had pre-diabetes. At 6 months, both D and D+E groups improved from baseline (p&lt;0.05 for all) but did not differ in their changes for body weight (D: -6.04 ± 4.54 kg; D+E: -6.68 ± 4.48 kg, p= 0.61 for the group differences in change), abdominal total fat (D: -101.93 ± 68.67 cm 2 ; D+E:-104.16 ± 72.37 cm 2 , p= 0.92), visceral fat (D:-25.53 ± 39.44 cm 2 ; D+E:,-23.24 ± 35.62 cm 2 , p=0.85), HbA1c (D:0.04 ± 0.46%; D+E:0.03 ± 0.63%, p=0.96), and VO 2 peak (D: 2.26 ± 3.92 ml/kg/min ; D+E:3.71 ± 2.65 ml/kg/min, p=0.11). In a multivariate analysis, adjusting for baseline visceral fat, T2D status, body weight loss and increases in aerobic fitness, a reduction in HbA1c (β=-0.49, p =0.007) was associated with a reduction in visceral fat (R 2 =0.34, p=0.02). Conclusion: The key finding was that diet or diet plus exercise-mediated reductions in visceral fat was associated with reduced HbA1c among individuals with T2D or pre-diabetes. These data contribute to growing body of evidence of the benefits of reducing abdominal obesity, in this case, resulting in better glycemic control in T2D and pre-diabetes.