tbuckley/cabot-search huggingface dataset:
Safety of pembrolizumab in combination with bevacizumab in recurrent glioblastoma (rGBM).
Authors: David A. Reardon, John Frederick De Groot, Howard Colman, Justin T Jordan, Mariza Daras, Jennifer Leigh Clarke, Phioanh Leia Nghiemphu, Sarah C. Gaffey, Katherine B. Peters
Journal: Journal of Clinical Oncology (2016)

2010 Background: Inhibition of vascular endothelial growth factor (VEGF) may enhance immunotherapies and decrease cerebral edema among GBM patients (pts). This multicenter, randomized phase 2 study determined safety and anti-tumor activity of pembrolizumab (P), a PD-1 blocking monoclonal antibody (Mab) with and without bevacizumab (Bev), a humanized anti-VEGF Mab among rGBM pts. Herein, we report the safety lead-in of this study. Methods: Pts in dose level 1 received P 200 mg Q3W and Bev 10 mg/kg Q2W. Dose de-escalation levels -1 and -2 increased the P interval to 4 and 6 weeks, respectively if dose level 1 exceeded maximum tolerated dose (MTD) based on standard 3+3 criteria. Eligible pts were ≥ 18 years, had 1or 2 recurrences, no prior anti-VEGF treatment, and KPS ≥ 70. The primary endpoint was MTD/recommended phase 2 dose (RP2D) determination based on dose limiting toxicity (DLT) during cycle 1. MRI scans were obtained after each 6-week cycle. Results: 6 pts were treated (4 male, 2 female) at1st (n = 2) or 2nd (n = 4) recurrence. Median age was 48 years (range: 27-79), and KPS = 90 (n = 3), 80 (n = 2) and 70 (n = 1). Median time from initial GBM diagnosis was 11 mo (range 4-61). Median duration on study was 3 mo (range 1-9.3). The most common adverse events that were at least probably related to study therapy were fatigue (grade 2, n = 2; grade 1, n = 2) and hypertension (grade 3, n = 2; grade 1, n = 1). No pt experienced a DLT and none required dose modification, interruption or discontinuation due to toxicity although Bev was electively held in 1 pt for a dental procedure. All pts discontinued study therapy due to progressive disease (PD). Best radiographic response was partial response (n = 1), stable disease (n = 2) and PD (n = 3). Two pts remain alive (327 and 328 days) while 4 have died. Median overall survival is 6.8 months. Accrual to the randomized phase 2 part of the study recently completed including 30 pts treated with P and 39 treated with P+Bev. Conclusions: This is the first study to report safety/tolerability of combination PD-1 plus VEGF blockade in GBM. P and Bev were safely combined when administered according to approved dosing schedules. No DLT or unexpected toxicity was encountered. Clinical Trial NCT02337491; Support – The Ben and Catherine Ivy Foundation Clinical trial information: NCT02337491.
Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin
Authors: I. Mittra, K. Pal, N. Pancholi, A. Shaikh, B. Rane, P. Tidke, S. Kirolikar, N.K. Khare, K. Agrawal, H. Nagare, N.K. Nair
Journal: Annals of Oncology (2017)
Opioid Use in Trauma
Authors: Crystal Webb, Amalia Cochran
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Abstract 2207: Significant Impact of the Total Cavopulmonary Connection Resistance on Cardiac Output and Exercise Performance in Single Ventricles
Authors: Kartik S Sundareswaran, Kerem Pekkan, Lakshmi Prasad Dasi, Hiroumi D Kitajima, Kevin Whitehead, Mark A Fogel, Ajit P Yoganathan
Journal: Circulation (2007)

Introduction: The resistance of the total cavopulmonary connection (TCPC) in single ventricle (SV) circulation has long been hypothesized as a critical contributing factor to their diminished exercise capacity. We investigate this hypothesis using a lumped parameter (LP) model coupled with cardiac catheterization (cath) and computational fluid dynamics (CFD). Methods: SV pulmonary vascular resistance (1.80 ± 0.83 WU) and systemic vascular resistance (18.4 ± 7.2 WU) were obtained from cath data on 48 pts with a TCPC. TCPC resistances (0.55 ± .24 WU, min=0.24, max = 0.93) were established from CFD simulations (n=13) and in vitro experiments (n=8) conducted on anatomically accurate TCPC models from MRI. Resistance and compliance values for the normal pediatric circulation were obtained from the literature. These values were then used in a LP model developed for both the normal and SV circulation. Results: For a biventricular circulation, the cardiac output (CO) dependence on resistance is negligible, but not for the SV circulation (Fig 1a ). Capacity to increase CO with heart rate is also severely reduced for the SV. At a simulated exercise HR of 140 beats per minute, the SV patient with the highest resistance (0.93 WU) had a significantly lower increase in cardiac output (22%) when compared to an SV patient with the lowest resistance (26%) and the normal circulation (67%) (Fig 1b ). Conclusion: Hemodynamic energy cascade in a SV circulation should not be judged by stereotypes of biventricular circulation. The impact of TCPC surgical pathway resistance on cardiac output at rest and exercise was significantly higher on SVs compared to biventricular circulation. Figure 1. Impact of TCPC resistance in single ventricle vs. normal circulation, specifically (a) resting cardiac output, and (b) exercise cardiac output
Evaluation des pratiques professionnelles: audit prospectif de 400 cholangio-pancréatographies rétrogrades endoscopiques
Authors: B Denis, A Peter
Journal: Endoscopy (2006)

L'évaluation des pratiques professionnelles est dorénavant une obligation légale. Le but de ce travail était d'évaluer les cholangio-pancréatographies rétrogrades endoscopiques (CPRE) réalisées dans notre unité dans le but d'en améliorer la qualité et la sécurité.
Focus on sharing individual patient data distracts from other ways of improving trial transparency
Authors: Tammy Hoffmann, Paul Glasziou, Elaine Beller, Ben Goldacre, Iain Chalmers
Journal: BMJ (2017)

The debate on sharing clinical trial data has been dominated by individual patient data. <b>Tammy Hoffmann and colleagues</b> argue that, although patient level data are important, a focus on the other simpler elements of trial transparency should be the first priority
Plasma caveolin-1 level: A prognostic marker for pancreatic cancer.
Authors: Nebi Serkan Demirci, Mutlu Dogan, Gokmen umut Erdem, Sabite Kacar, Turan Turhan, Fatma Meric Yilmaz, Saadettin Kilickap, Lutfi Can Cigirgan, Ertugrul Kayacetin, Nurullah Zengin
Journal: Journal of Clinical Oncology (2016)

e15706 Background: Evaluation of the prognostic significance of plasma caveolin-1(cav1) and its relation with survival & response rates in metastatic pancreatic cancer(MPC). Methods: The patients followed-up between March 2013 & April 2015 were enrolled. Plasma samples were collected from 41 MPC patients (group 1), 48 patients with chronic pancreatitis (group 2) & 41 healthy subjects (group 3). Group 1 had cisplatin & gemcitabine (cisplatin 75 mg/m2 D1, gemcitabine 1200mg/m2 D1 & D8, q3w). Plasma cav1 was evaluated before and after 3 cycles of chemotherapy by ELISA method. Results: Median OS of MPC patients was 5.6 months (0.4-33.8) with a median follow-up of 4.2 months (0.03-33.8). Median cav1 level was 13.8 ng/mL (4-96) for group 1 &12.2ng/mL (3-30.4) for group 3(p:0.009). Median caveolin-1 levels of group 1 & 3 and group 2 & 3 were similar (p:0.390, p:0.135). Median chemotherapy cycle was 3 (1-6). The cut-off value for cav1 level was calculated as 11.6 ng/mL by ROC (Receiver Operating Characteristic) curve. Basal Ca 19-9, CEA and LDH levels had no effect on survival. There was no relation between plasma cav1 level and these parameters. Median OS & DFS were 5 & 2,4 months for those with high basal plasma cav1 level whilst they were as 10.5 & 9,4 months for the others with low plasma cav1 level (p = 0.008, p = 0.002). 23 of 41 MPC patients could have completed at least 3 cycles of chemotherapy (group 1a). Median basal plasma cav1 level was 13.8 ng/mL (4-96) for group 1 whereas it was 13 ng/mL (9.4-96) for group 1a. The patients who had high basal plasma cav1 level still had high plasma caveolin-1 level even after chemotherapy with a worse trend towards lower response rates (p:0.086). Conclusions: We consider that basal plasma cav1 level seems to be an independent poor prognostic factor for MPC. Although the prognostic significance of cav1 overexpression in the tumor tissue has been established previously, to best of our knowledge, this is the first study evaluating the prognostic significance of plasma cav1 level as a prognostic factor in MPC. Evaluation of cav-1 in plasma samples is easier and cheaper than immunhistochemical staining on tumor tissue. In conclusion, plasma cav1 level might be used as a cost-effective poor prognostic factor for MPC.
Occult Renal Granulomatous Inflammatory Lesions in Granulomatosis with Polyangiitis Detected by 18F-FDG PET/CT
Authors: Zhanli Fu, Meng Liu, Ziao Li, Jin Zhang, Qian Li
Journal: Clinical Nuclear Medicine (2017)

A 33-year-old woman with a 7-month history of granulomatosis with polyangiitis 18F-FDG PET/CT scan due to low-grade intermittent fever and elevation of serum inflammatory markers, which revealed multiple hypermetabolic lesions in bilateral kidneys. Biopsy of a lesion showed granulomatosis with polyangiitis, consistent with renal involvement of granulomatosis with polyangiitis.
Antibiotic Resistance in Acne Treatment
Authors: Brandon L. Adler, Heather Kornmehl, April W. Armstrong
Journal: JAMA Dermatology (2017)

What is the evidence for antibiotic resistance in acne, and how does resistance affect treatment?Use of topical and systemic antibiotics for acne is associated with formation of resistance in Propionibacterium acnes and other bacteria, with clinical consequences. Guidelines recommend resistance reduction strategies including avoidance of antibiotic monotherapy, combination treatment with topical modalities, and limiting the duration of oral antibiotic use.
Factors modulating worry and risk perception of breast cancer in a prevention trial of low dose tamoxifen in postmenopausal hormone users.
Authors: Gabriella Rondanina, Matteo Puntoni, Aliana Guerrieri-Gonzaga, Domenico Marra, Bernardo Bonanni, Andrea De Censi
Journal: Journal of Clinical Oncology (2016)

e13048 Background: We previously showed that refusal to participate in a breast cancer prevention trial was associated with higher worry about breast cancer. Given this counterintuitive finding, we studied which factors influenced worry and risk perception of breast cancer. Methods: We assessed the relationships of breast cancer worry and risk perception with age, age at menopause, Gail risk score, education, current HRT use, mammographic screening, BMI, smoking, physical activity, alcohol use, anxiety and depression in 457 postmenopausal women who were eligible to participate in a prevention trial of low-dose tamoxifen. Results: Women with menopause < 48 years were more worried about breast cancer than women with menopause > 52 years (OR = 5.9, 95% CI, 1.5-23.2). There was a significant inverse linear trend between age at menopause (as continuous variable) and breast cancer worry (p-trend = .001). Worry was also associated with high absolute risk perception and former smoking. Women > 60 years or with moderate or severe depression had a higher increased perception of breast cancer risk. Women with heightened breast cancer worry had a higher risk perception (p-trend < .001). Smoke, overweight and no exercise were associated with a 3-fold absolute risk perception of breast cancer. Use of HRT and parity were associated with a trend to an increased risk perception. Conclusions: The inverse association between early menopause and worry about breast cancer is in contrast with the known protective effect of early menopause on breast cancer risk and seems to reflect a feeling of aging and disease vulnerability. Our findings indicate that the affective construct of worry about cancer is linked but different from the cognitive construct of cancer risk perception, which is more adherent to biology. Since affective factors are engaged in decision making and health promotion changes, increasing breast cancer risk awareness in subjects high in worry without a plan of emotional coping may be counterproductive because of avoidant attitudes. A better understanding of the emotional factors that modulate the decision making process can potentially improve adherence to breast cancer prevention programs. Clinical trial information: NCT01579734.
Depth electrode neurofeedback with a virtual reality interface
Authors: Hagar Grazya Yamin, Tomer Gazit, Natalia Tchemodanov, Gal Raz, Gilan Jackont, Fred Charles, Itzhak Fried, Talma Hendler, Marc Cavazza
Journal: Brain-Computer Interfaces (2017)

Invasive brain–computer interfaces (BCI) provide better signal quality in terms of spatial localization, frequencies and signal/noise ratio, in addition to giving access to deep brain regions that play important roles in cognitive or affective processes. Despite some anecdotal attempts, little work has explored the possibility of integrating such BCI input into more sophisticated interactive systems like those which can be developed with game engines. In this article, we integrated an amygdala depth electrode recorder with a virtual environment controlling a virtual crowd. Subjects were asked to down regulate their amygdala using the level of unrest in the virtual room as feedback on how successful they were. We report early results which suggest that users adapt very easily to this paradigm and that the timing and fluctuations of amygdala activity during self-regulation can be matched by crowd animation in the virtual room. This suggests that depth electrodes could also serve as high-performance affective interfaces, notwithstanding their strictly limited availability, justified on medical grounds only.
Tissue transglutaminase and coeliac disease
Authors: E Thornton, M Lynskey, J Donlon, F Stevens
Journal: Endoscopy (2006)

Coeliac disease (CD) is a permanent intolerance to dietary gluten peptides occurring in genetically predisposed individuals. Ingestion of gluten results in inflammation and effacement of mucosal villi, with consequent mal-absorption of nutrients. Tissue transglutaminase (TG2) has been identified as a major auto-antigen in CD. Earlier reports have presented evidence of elevated activity of TG2 in coeliac biopsy samples and that, by deamidating gliadin, TG2 may enhance intestinal T-cell recognition. Antibodies to gliadin, endomysium and TG2 are markers for CD. Using a large pool of coeliac and control samples we have not found any significant difference in the cross-linking activity of TG2 in coeliacs and non-symptomatic controls. However, we have observed subtle differences in the kinetic properties of TG2 in coeliac samples. We have also performed western blots and observed a greater prevalence of a 60kDa form of TG2 in controls. CD and control TG2 have differential overall charge consistent with a lower isoelectric point in control samples.
Safety and antitumor activity of weekly carboplatin plus paclitaxel in metastatic breast cancer: A ten years, single-institution, retrospective analysis.
Authors: Claudio Vernieri, Monica Milano, Alessia Mennitto, Claudia Maggi, Benvenuto Ferrari, Lucia Rinaldi, Roberta Mennitto, Claudia Stefanetti, Barbara Re, Gabriella Mariani, Giuseppe Capri, Giulia Valeria Bianchi, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2017)

e12556 Background: Safety and activity of weekly carboplatin plus paclitaxel in patients (pts) with metastatic breast cancer (mBC) are poorly known. Nevertheless, taxane-based chemotherapy (ChT) is the milestone in mBC treatment. In this retrospective analysis, we report the safety and clinical activity of this combination in a consecutive series of pts treated at IRCCS Fondazione Istituto Nazionale dei Tumori in Milan in the last decade. Methods: We collecteddata on mBC patients treated between January 2007 and December 2016 with carboplatin AUC 2 plus paclitaxel 80 mg/m 2 on days 1 and 8, every three weeks. Selection criteria were: ECOG 0-1; evaluable and/or measurable mBC; known estrogen and progesterone receptors (ER/PgR) status and HER2 expression levels. 274 pts fulfilled the selection criteria, and 265 pts were evaluable for response and survival. Response was assessed according to RECIST criteria. Results: The median number of administered cycles was 6 (range 1-17). 66.4% and 88.3% of pts had received taxanes or antracyclines, respectively, as an adjuvant treatment or in the metastatic setting. 97% of HER2+ pts received trastuzumab concomitant with ChT. Among patients with ER/PgR-positive tumors, 42.8% received different endocrine treatments as maintenance therapy after achieving the best response with ChT or due inacceptable toxicity. Hematological and gastrointestinal toxicities were the most frequent adverse events (AEs), and were severe in 19% and 1.2% of pts, respectively. In particular, G3-G4 neutropenia and febrile neutropenia occurred in 16.8 % and 1.9 % of pts, respectively. 10.2% of pts discontinued the treatment because of toxicity. The objective response rate was 44.8% in the overall population, with median progression free survival (mPFS) of 8.6 months and median overall survival (mOS) of 23.7 months. Conclusions: Weekly carboplatin plus paclitaxel is a well-tolerated and active regimen across all different molecular subgroups of mBC. [Table: see text]
Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells
Authors: Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F. Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter
Journal: Cancer Research (2017)

Abstract Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C &amp;gt; 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal or gemcitabine treatment, but depriving PDAC cells of nutrients before gemcitabine treatment attenuated this effect. Mechanistic investigations based on RNAi or CRISPR approaches implicated the RNA binding protein HuR in preserving survival under nutrient withdrawal, with or without gemcitabine. Notably, RNA deep sequencing and functional analyses in HuR-deficient PDAC cell lines identified isocitrate dehydrogenase 1 (IDH1) as the sole antioxidant enzyme under HuR regulation. HuR-deficient PDAC cells lacked the ability to engraft successfully in immunocompromised mice, but IDH1 overexpression in these cells was sufficient to fully restore chemoresistance under low nutrient conditions. Overall, our findings highlight the HuR–IDH1 regulatory axis as a critical, actionable therapeutic target in pancreatic cancer. Cancer Res; 77(16); 4460–71. ©2017 AACR.
Abstract 13967: Development of Pharmacogenomic Algorithm for Warfarin Dose Monitoring in Indian Patients
Authors: Pavani Addepalli, Naushad Shaik Mohammad, Ramesh Kumar T, Amaresh Rao M, Ramakrishna Pinjala, Vijay Kumar Kutala
Journal: Circulation (2010)

Introduction: Wide inter-individual variation in the dose of warfarin has become a serious cause of concern, which is attributable to physiological [age, body mass index, gender] and genetic factor...
Off-label Use of High-Risk Cardiovascular Devices
Authors: Karen E. Joynt, Daniel B. Kramer
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal