tbuckley/cabot-search huggingface dataset:
A phase Ib/II clinical trial of a novel oxygen therapeutic in chemoradiation of glioblastoma.
Authors: Evan C. Unger, Jason D. Lickliter, Jeremy Ruben, Ross Jennens, Ganessan Kichenadasse, Cecelia Gzell, Ralph Mason, Raymond Carmody, Jennifer Becker, Heling Zhou, Michael Sellenger, Olivia Longacre, Kaitlin Graham, Baldassarre Stea
Journal: Journal of Clinical Oncology (2017)

2561 Background: Tumor hypoxia limits the response of glioblastoma multiforme (GBM) to radiotherapy (RT) and chemotherapy (temozolomide[TMZ]). Additionally, patient biomarkers are strong predictors of responsiveness to TMZ. The purpose of this study is to evaluate the use of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM and stratify the results based on predicted TMZ response. Methods: 11 adult GBM patients have been enrolled. Patients were administered DDFPe via IV infusion (2% w/vol at doses of 0.05, 0.1 or 0.17 mL/kg) an hour prior to each 2 Gy fraction of RT (30 fractions over 6-weeks) with supplemental oxygen. Patients also received standard concurrent and adjuvant TMZ. To confirm tumor re-oxygenation, patients underwent TOLD MRI before and after DDFPe administration. Archived tumor specimens were studied with GliomaSTRAT assay for methylated genes predictive of response. Patients were also studied with serial MRI scans per standard of care and followed for survival. Results: There were minimal acute adverse events related to DDFPe administration. One patient at each of dose levels 0.1 and 0.17 mL/kg developed symptomatic radiation necrosis, which was judged to be related to DDFPe. Enrollment has continued at the 0.1 mL/kg dose without additional significant DDFPe-related toxicity. TOLD MRI showed significant decrease in T 1 of tumor tissue consistent with tumor re-oxygenation (p=0.015) with no significant change in oxygenation of normal brain tissue. Historically, the average overall survival for GBM patients, for both TMZ responders and non-responders, is about 14.6 months. The progress chart for patient overall survival is listed below, 4 patients have died. All other patients are alive. Conclusions: DDFPe is a promising oxygen therapeutic for reversing tumor hypoxia. A Phase II study is being planned to assess its effectiveness. Clinical trial information: NCT02189109. [Table: see text]
Whole Transcriptome Sequencing Identified a Distinct Subtype of Acute Lymphoblastic Leukemia with Abnormalities of CREBBP and EP300
Authors: Hui Zhang, Maoxiang Qian, Shirley, Kow Yin Kham, Shuguang Liu, Chuang Jiang, Xujie Zhao, Yi Lu, Ting-Nien Lin, Ranran Zhang, Takaya Moriyama, Zhaohong Yin, Lei Shi, Zhenhua Li, Kean-Hui Chiew, Zhiwei Chen, Bhojwani Deepa, Shuhong Shen, Huyong Zheng, Ching-Hon Pui, Allen Eng Juh Yeoh, Jun J. Yang
Journal: Blood (2016)
Unusual pattern of <i>KRAS</i> mutations in inner city patients with NSCLC.
Authors: Yuanquan Yang, Janaki Neela Sharma, Balazs Halmos, Rasim A. Gucalp, Missak Haigentz, Stuart H. Packer, Steven M. Keller, Changcheng Zhu, Roman Perez-Soler, Haiying Cheng
Journal: Journal of Clinical Oncology (2016)

e20033 Background: KRAS mutations (mut) occur in 15-25% of non-squamous NSCLC and may be associated with poor survival and primary EGFR TKI resistance. Distinct subgroups of KRAS-mut non-squamous NSCLC may have different tumor biology and clinical outcomes. Very limited data are available for KRAS mut patterns in different racial groups. Montefiore Medical Center (MMC), a community-based academic center located in New York City, treats a large minority population. We initiated reflex molecular testing on all non-squamous NSCLC patients (pts) in 01/2012. Methods: We retrospectively reviewed our cancer registry database from 01/2009 to 12/2014 and analyzed all non-squamous NSCLC pts with pathology available in our system for rates and patterns of KRAS mut. KRAS mut testing was performed by PCR-based technology. Results: 1161 pts with NSCLC had their pathology diagnosis at MMC from 2009 to 2014 and 264 were tested for KRAS mut. The KRAS mut rate was 44% (115/264) for all races, 42% (48/110) for African Americans (AA) and 47% (54/115) for Whites. When corrected for selection bias to include patients with EGFR mutations who were not tested for KRAS, the KRAS mut rate was 36% (115/320) for all races, 36% (48/134) for AA and 37% (54/145) for Whites. Around 40% of KRAS-mut patients had stage I disease, while 37% had stage IV. Only 6% of the patients with KRAS mut were never-smokers. The most common KRAS mut were G12C (46%) and G12V (25%). Other mutations included G12D, G13C, G12A, G13D, G12S and G12R. One pt had a complex mut of G12C and G13D. The median overall survival was 13 months for the G12C (n = 53), 14 months for G12V (n = 29) and 18 months for the other mutation subgroups (n = 33). Conclusions: KRAS-mut NSCLCs are very prevalent in our pt population in all racial groups which indicates that its higher than expected frequency is not driven by racial influences but more likely by socioeconomic and smoking status. Given this strikingly high rate of a very aggressive, treatment-resistant form of lung cancer, increased efforts should be placed not only on therapy but also on smoking cessation and screening initiatives targeted for similar poor, inner city patient populations.
Antacid therapy in idiopathic pulmonary fibrosis: more questions than answers?
Authors: Kerri A Johannson, Irina Strâmbu, Claudia Ravaglia, Jan C Grutters, Claudia Valenzuela, Nesrin Mogulkoc, Fabrizio Luppi, Luca Richeldi, Athol U Wells, Carlo Vancheri, Michael Kreuter, Carlo Albera, Katerina M. Antoniou, Goksel Altinisik, Elisabeth Bendstrup, Benjamin Bondue, Raphael Borie, Kevin K. Brown, Philippe Camus, Diego Castillo, Harold R. Collard, Vincent Cottin, Nunzio Crimi, Giovanni Ferrara, Aryeh Fischer, Jack Gauldie, Thomas Geiser, Andreas Guenther, Nathan Hambly, David M. Hansell, Sergio Harari, Mark G. Jones, Michael Keane, Brett Ley, Toby M. Maher, Maria Molina-Molina, Stefano Palmucci, Venerino Poletti, Antje Prasse, Paola Rottoli, Paolo Spagnolo, Martina Sterclova, Sebastiano Torrisi, Eliza Tsitoura, Martina Vasakova, Simon L. Walsh, Marlies S. Wijsenbeek, Wim A. Wuyts
Journal: The Lancet Respiratory Medicine (2017)
HIV Testing, Linkage to HIV Medical Care, and Interviews for Partner Services Among Women — 61 Health Department Jurisdictions, United States, Puerto Rico, and the U.S. Virgin Islands, 2015
Authors: Renee Stein, Songli Xu, Mariette Marano, Weston Williams, Qi Cheng, Adanze Eke, Andrea Moore, Guoshen Wang
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Diagnoses of human immunodeficiency virus (HIV) infection among women declined 17% during 2011-2015, and a total of 7,498 women received a diagnosis of HIV infection in 2015 (1). Although black or African American (black) women accounted for only 12% of the U.S. female population, 60% of women with newly diagnosed HIV infection were black (1,2). By the end of 2014, an estimated 255,900 women were living with HIV infection (3), including approximately 12% who did not know they were infected; in addition, approximately 45% of women who had received a diagnosis had not achieved viral suppression (3). HIV testing is an important public health strategy for identifying women with HIV infection and linking them to HIV medical care. Analysis of CDC-funded program data submitted by 61 health departments in 2015 indicated that among 4,749 women tested who received a diagnosis of HIV infection, 2,951 (62%) had received a diagnosis in the past (previous diagnosis), and 1,798 (38%) were receiving a diagnosis for the first time (new diagnosis). Of those who had received a previous diagnosis, 87% were not in HIV medical care at the time of the current test. Testing and identifying women who are living with HIV infection but who are not in care (regardless of when they received their first diagnosis) and rapidly linking them to care so they can receive antiretroviral therapy and become virally suppressed are essential for reducing HIV infection among all women.
Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA/bioglass components – Guidance of the inflammatory response as basis for osteochondral regeneration
Authors: Mike Barbeck, Tiziano Serra, Patrick Booms, Sanja Stojanovic, Stevo Najman, Elisabeth Engel, Robert Sader, Charles James Kirkpatrick, Melba Navarro, Shahram Ghanaati
Journal: Bioactive Materials (2017)

The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the (molecular) weight loss and the morphological and mechanical variations after immersion in SBF. The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods. Both scaffold parts kept their structural integrity, while changes in morphology were observed, especially for the PLA/G5 scaffold. Mechanical properties decreased with progressive degradation, while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds. The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds, while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization. Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers. Altogether, the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength. Furthermore, the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs, while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration. Thus, this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects. Additionally, the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.
Using ultrasound and palpation for predicting axillary lymph node status following neoadjuvant chemotherapy: Results from the prospective multi-center SENTINA trial.
Authors: Lukas Schwentner, Gisela Helms, Valentina Nekljudova, Beyhan Ataseven, Ingo Bauerfeind, Nina Ditsch, Tanja N. Fehm, Barbara Fleige, Maik Hauschild, Joerg Heil, Sherko Kümmel, Annette Lebeau, Cornelia Liedtke, Sibylle Loibl, Sabine Schmatloch, Peter Schrenk, Annette Staebler, Michael Untch, Gunter Von Minckwitz, Thorsten Kühn
Journal: Journal of Clinical Oncology (2016)

1054 Background: Prediction of downstaging of axillary lymph nodes following neoadjuvant chemotherapy (NACT) in previously cN1 patients is important for therapy management. This study aims to investigate the predictive value of palpation in axillary ultrasound in formerly cN1 patients following NACT in the prospective multi-center SENTINA study. Methods: The SENTINA trial is a 4-arm prospective multicenter cohort study designed to examine the Detection-Rate (DR) and False-Negativ-Rate (FNR) of a standardized Sentinel-Node-Biopsy (SLNB)-procedure in the neoadjuvant setting. In SENTINA, patients were categorized into four treatment arms according to axillary staging results before and after NACT using palpation, ultrasound (+/-FineNeedleBiopsy/CoreNeedleBiopsy). In this subset analysis we only included patients and their clinical evaluated axillary lymph node status from arm C (cN1 converted to cN0 after NACT) and D (cN1 remained cN1 after NACT) following NACT. Results: 1240 patients from 104 institutions entered the trial. 715 (arm C n = 592; arm D n = 123) patients, who presented initially with suspicious nodes were included into arm C/D and received evaluation following NACT using palpation und ultrasound. Palpation alone revealed a true negative result in 307 patients, true positive in 32 patients, false negative in 352 patients, demonstrating a FNR of 91.7% and a negative predictive value (NPV) of 46.6%. Ultrasound alone was associated with 299 true negative, 93 true positive and 296 false negative results following NACT with a FNR of 76.1%, and a NPV of 50.3%. Even the combined evaluation of palpation and ultrasound resulted in only 298 true negative (95 true positive, 294 false negative) results, providing a FNR of 75.6%, and a NPV of 50.3%. These results were similar to the result of ultrasound alone, indicating that investigators mainly decided on the basis of the ultrasound finding. Also investigators overall evaluation involving both methods demonstrated more than 2 involved nodes in 24.2% of patients with a cN0 axilla following NACT. Conclusions: Evaluation of the axilla by palpation and ultrasound is negatively impacted by NACT.
Final results of a first-in-human study evaluating the safety, pharmacology and initial efficacy of MM-151, an oligoclonal anti-EGFR antibody in patients with refractory solid tumors.
Authors: Wael A. Harb, Alex A. Adjei, Murali Beeram, J. Marc Pipas, Sharon Chen, Andrea Valencia, Victoria Rimkunas, Ty McClure, Jeffrey D. Kearns, Rachel Nering, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2016)

2518 Background: MM-151 is a mixture of three IgG1 antibodies designed to bind simultaneously to non-overlapping EGFR epitopes and inhibit ligand-mediated signal amplification, downregulate EGFR expression, and enhance immune-effector activities (ADCC, CDC). A Phase 1 study was completed to assess safety, tolerability, pharmacology and preliminary clinical activity of MM-151 alone and in combination with irinotecan. Methods: This study evaluated MM-151 when administered as a monotherapy and in combination with irinotecan. An expansion cohort was also enrolled to evaluate clinical activity in EGFR-refractory metastatic CRC patients (pts). Subset analyses and additional biomarker evaluations were performed in EGFR-driven indications. Results: A total of 111 patients were enrolled (87 pts on monotherapy). The most common tumor types were CRC (43 [39%]), NSCLC (11 [10%]) and SCCHN (14 [13%]). Weekly dose selection was previously reported. Reported here are final safety and biomarker data. Most adverse events were CTCAE Grades 1 and 2. The most common Grade 3 (G3) or higher non-infusion related reaction (IRR) AEs included EGFR-pathway toxicities such as maculopapular rash (11 [9.9%]), hypomagnesemia (10 [9%]), general rash (8 [7.2%]) and diarrhea (8 [7.2%]). G3 IRRs occurred in 8/57 (14%) of pts enrolled at the non-optimized dosing guidelines vs. 1/57 (1.7%) of pts in the optimized dosing cohorts. Biomarker analyses revealed a complex set of resistance mechanisms. Notably, clinically meaningful durations were achieved in patients presenting with multiple resistance markers, including RAS/RAF mutations. Within a CRC subset, 13/29 (45%) achieved SD or PR at 3 cycles of treatment and 5/29 (17%) achieved a PR, with highly durable responses and disease control. Conclusions: Results to date demonstrate that MM-151 has an acceptable tolerability profile. Preliminary indications of objective clinical activity across both the EGFR-refractory and naïve populations suggest potential for broad effect. Biomarker profiling also suggests that MM-151 may overcome mechanisms of resistance. Further clinical evaluation is underway. Clinical trial information: NCT01520389.
Addition of pazopanib (PZ) to endocrine therapy in hormone resistant advanced breast cancer (ABC).
Authors: Melanie Catherine Majure, Ariadna Gasol Cudós, Austin Nicholas Angelidakis, Michelle E. Melisko, Ariel R. Karwat, Amy Jo Chien, Andrei Goga, Mark M. Moasser, John W. Park, Amy N. DeLuca, Hope S. Rugo
Journal: Journal of Clinical Oncology (2016)

560 Background: A major limitation of endocrine therapy is development of resistance in hormone receptor positive (HR+) ABC. Preclinical data suggests that higher levels of vascular endothelial growth factor (VEGF) are associated with endocrine therapy resistance. We conducted a phase II trial to evaluate the clinical benefit (CB) from adding PZ, a VEGF receptor tyrosine kinase inhibitor (TKI) to nonsteroidal aromatase inhibitors (NSAIs) in pts with ABC resistant to NSAIs. Methods: Eligibility included postmenopausal women with HR+ ABC and progressive disease (PD) after at least one month of NSAIs. Treatment was PZ 800 mg/day plus either letrozole or anastrozole. The primary endpoint was clinical benefit rate at 12 weeks (CBR12, wks). Secondary endpoints were PFS and safety. A CBR of 20% was considered a clinically meaningful comparison to the expected CBR of < 5% with continued NSAIs after PD. Using a 2-stage design, stable disease in at least 1 of the first 13 pts allowed continued enrollment to a planned 28. Results: 32 pts were enrolled; 28 are evaluable for study endpoints. The median age was 58 years (range: 41-77). Pts were heavily pre-treated: mean of 3 and 2 lines of prior hormone (range 1-6) and chemotherapy (range 0-8), respectively. 8 pts (28.6%) stopped treatment due to toxicity including hypertension (HTN), fever, transaminitis, and pulmonary embolism (PE); 6 pts progressed before wk 12. CBR12 was 46.4% (12 SD, 1 PR); CBR24 was 25% (5 SD, 2 PR). Median PFS for pts with CBR12 was 24 wks; 7 pts had PFS > 6 months (24, 32, 36, 36, 48, 96 and 144 wks). 2 pts remain on study at 96 and 144 wks. The most common grade 1/2 adverse events (AE) were nausea (56%), fatigue (44%), diarrhea (44%), and anorexia (30%). Grade 3/4 AE included HTN (3/28; 11%), transaminitis (3/28; 11%), headache (2/28; 7%), and PE (1/28; 4%). Conclusions: The addition of PZ to NSAIs resulted in a CBR12 of 46.4%, and a CBR24 of 25% in pts with heavily pre-treated hormone resistant ABC. These results support clinical efficacy of antiangiogenic TKI in HR+ ABC, and suggest benefit in hormone resistant disease. Expected toxicities resulted in early discontinuation in 28.6%, which limited drug exposure. Evaluation of biomarkers and immune signatures is ongoing. Clinical trial information: NCT01466972.
Infective Endocarditis After Transcatheter Aortic Valve Implantation
Authors: Ignacio J. Amat-Santos, David Messika-Zeitoun, Helene Eltchaninoff, Samir Kapadia, Stamatios Lerakis, Asim N. Cheema, Enrique Gutiérrez-Ibanes, Antonio J. Munoz-Garcia, Manuel Pan, John G. Webb, Howard C. Herrmann, Susheel Kodali, Luis Nombela-Franco, Corrado Tamburino, Hasan Jilaihawi, Jean-Bernard Masson, Fabio Sandoli de Brito, Maria Cristina Ferreira, Valter Correa Lima, José Armando Mangione, Bernard Iung, Alec Vahanian, Eric Durand, E. Murat Tuzcu, Salim S. Hayek, Rocio Angulo-Llanos, Juan J. Gómez-Doblas, Juan Carlos Castillo, Danny Dvir, Martin B. Leon, Eulogio Garcia, Javier Cobiella, Isidre Vilacosta, Marco Barbanti, Raj R. Makkar, Henrique Barbosa Ribeiro, Marina Urena, Eric Dumont, Philippe Pibarot, Javier Lopez, Alberto San Roman, Josep Rodés-Cabau
Journal: Circulation (2015)

Background— We aimed to determine the incidence, predictors, clinical characteristics, management, and outcomes of infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI). Methods and Results— This multicenter registry included 53 patients (mean age, 79±8 years; men, 57%) who suffered IE after TAVI of 7944 patients after a mean follow-up of 1.1±1.2 years (incidence, 0.67%, 0.50% within the first year after TAVI). Mean time from TAVI was 6 months (interquartile range, 1–14 months). Orotracheal intubation (hazard ratio, 3.87; 95% confidence interval, 1.55–9.64; P =0.004) and the self-expandable CoreValve system (hazard ratio, 3.12; 95% confidence interval, 1.37–7.14; P =0.007) were associated with IE (multivariate analysis including 3067 patients with individual data). The most frequent causal microorganisms were coagulase-negative staphylococci (24%), followed by Staphylococcus aureus (21%) and enterococci (21%). Vegetations were present in 77% of patients (transcatheter valve leaflets, 39%; stent frame, 17%; mitral valve, 21%). At least 1 complication of IE occurred in 87% of patients (heart failure in 68%). However, only 11% of patients underwent valve intervention (valve explantation and valve-in-valve procedure in 4 and 2 patients, respectively). The mortality rate in hospital was 47.2% and increased to 66% at the 1-year follow-up. IE complications such as heart failure ( P =0.037) and septic shock ( P =0.002) were associated with increased in-hospital mortality. Conclusions— The incidence of IE at 1 year after TAVI was 0.50%, and the risk increased with the use of orotracheal intubation and a self-expandable valve system. Staphylococci and enterococci were the most common agents. Although most patients presented at least 1 complication of IE, valve intervention was performed in a minority of patients, and nearly half of the patients died during the hospitalization period.
Post-infantile giant cell hepatitis: the role of steroids
Authors: A Zaheer, G Macdonald, S Shah, E Connealley, D Kelleher, N Mahmud, S Norris
Journal: Endoscopy (2006)

Introduction: Giant cell Hepatitis (GCH) is rare in adults. Various conditions are associated with GCH, however pathogenesis remains unclear. GCH has an ominous prognosis with limited treatment options.
The RIP3-RIP1-NF-κB signaling axis is dispensable for necroptotic cells to elicit cross-priming of CD8+ T cells
Authors: Junming Ren, Xian Jia, Yihao Zhao, Wenke Shi, Jiongcong Lu, Yingying Zhang, Jianfeng Wu, Bo Liang, Rui Wu, Guo Fu, Jiahuai Han
Journal: Cellular and Molecular Immunology (2017)