tbuckley/cabot-search huggingface dataset:
Correlation of epidermal growth factor receptor mutation status in plasma and tissue samples of patients with lung cancer
Authors: C. Son
Journal: Annals of Oncology (2019)

Background: Somatic mutations of the gene encoding epidermal growth factor receptor (EGFR) are detected in approximately 30%–50% of patients with non-small cell lung cancers (NSCLC), so detection of EGFR mutation is the pivotal step of treatment in patients with advanced NSCLC. However, difficulty in obtaining sufficient tissue and bias from the heterogeneity of the tumor samples are the major obstacles. Although analyzing EGFR with circulating tumor DNA (ctDNA) in plasma is a breakthrough, accuracy is the problem in variable methods. Peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve analysis (PANAMutyper®) is a novel and highly sensitive method of detecting EGFR mutation in tumor tissues. This study was designed to evaluate PANAMutyper® for detecting EGFR mutation with ctDNA of patients with lung cancer. Methods: EGFR mutation status detected by PNA clamp with tissue samples and by PANAMutyper® with ctDNA was compared. Tissue biopsy was done in 158 patients with lung tumor, in which 23 cases were excluded and 135 cases were enrolled. All the plasma samples of the cases with mutant EGFR in tissue samples were verified by an already known highly sensitive method of droplet digital polymerase chain reaction (ddPCR). Results: EGFR mutation rate was 23.0% (31/135) in overall patients. The concordance rate of tissue and plasma samples was 91.9% (124/135). The sensitivity, specificity, negative predictive value, and positive predictive value were 64.5%, 100.0%, 90.4%, and 100.0%, respectively, according to the tissue samples as a standard. Conclusions: PANAMutyper® method was not inferior to ddPCR for the detection of EGFR mutation including T790M with ctDNA. These results suggest that the detection of EGFR mutation status using ctDNA in plasma by PANAMutyper® is a feasible test prior to tissue biopsy. Legal entity responsible for the study: Choonhee Son. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
HIV Testing and Sexual Health Among Black African Men and Women in London, United Kingdom
Authors: Ibidun Fakoya, Louise Logan, Winnie Ssanyu-Sseruma, Alison Howarth, Gary Murphy, Anne M. Johnson, Anthony Nardone, Alison J. Rodger, Fiona Burns
Journal: JAMA Network Open (2019)

Black African adults are disproportionately affected by HIV in the United Kingdom. Many within this population acquire HIV after migration or are diagnosed late. Data are needed to inform targeted interventions to increase HIV testing and prevention in this population.
Abstract 18072: Low Endothelial Shear Stress is Associated With High-Risk Coronary Plaque Characteristics in Humans: A Three-Dimensional Frequency-Domain Optical Coherence Tomography Study
Authors: Rocco Vergallo, Michail I Papafaklis, Haibo Jia, Christos V Bourantas, Iris McNulty, Hang Lee, Bo Yu, Italo Porto, Luigi M Biasucci, Filippo Crea, Charles L Feldman, Lampros K Michalis, Peter H Stone, Ik-Kyung Jang
Journal: Circulation (2013)

Introduction: Large lipid pool and thin fibrous cap are characteristics of plaques at high-risk for rupture resulting in adverse cardiac events. However, the local factors associated with the development of a rupture-prone plaque phenotype are not well known in humans. Endothelial shear stress (ESS) plays a major role in the development and progression of atherosclerotic plaques. We sought to investigate in vivo the relationship between computed ESS and plaque characteristics assessed by frequency-domain optical coherence tomography (FD-OCT). Methods: Three-dimensional coronary artery reconstruction was performed in 9 patients (4 left anterior descending, 2 left circumflex and 3 right coronary arteries) presenting with acute coronary syndrome using FD-OCT and coronary angiography. Each coronary artery was divided into sequential 3-mm segments, and each segment was analyzed for the assessment of predominant local ESS value by computational fluid dynamics and morphologic characteristics by FD-OCT. A total of 58 non-culprit segments without significant stenosis were evaluated. Results: Segments with low ESS (&lt;1 Pascal [Pa]) had significantly larger lipid arc (120.9° ± 36.2° vs. 82.5° ± 22.0°, p = 0.015) and thinner fibrous cap (172.7 ± 69.4 μm vs. 264.5 ± 110.5 μm, p = 0.008) compared to segments with higher ESS (≥1 Pa) (Figure). Segments with macrophage accumulation tended to have lower local ESS values (0.98 ± 0.42 Pa vs. 1.62 ± 1.50 Pa, p = 0.170) compared to those without macrophage accumulation. Similarly, segments with lipid-rich plaque (lipid arc &gt;90°) showed lower ESS values compared to those without lipid-rich plaque (1.06 ± 1.02 Pa vs. 1.78 ± 1.54 Pa, p = 0.177). Conclusions: The present study shows that coronary regions exposed to low ESS are characterized by larger lipid burden and thinner fibrous cap, suggesting that low ESS has a critical role in the development of vulnerable plaques.
Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia
Authors: Andrea DeCensi, Matteo Puntoni, Aliana Guerrieri-Gonzaga, Silvia Caviglia, Franca Avino, Laura Cortesi, Cristiana Taverniti, Maria Grazia Pacquola, Fabio Falcini, Marcella Gulisano, Maria Digennaro, Anna Cariello, Katia Cagossi, Graziella Pinotti, Matteo Lazzeroni, Davide Serrano, Daniela Branchi, Sara Campora, Marilena Petrera, Tania Buttiron Webber, Luca Boni, Bernardo Bonanni
Journal: Journal of Clinical Oncology (2019)

Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose.We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ.Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen (P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo.Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.
Current treatment patterns in patients with metastatic melanoma: A retrospective claims database analysis in the United States (US).
Authors: Yaozhu J. Chen, Qiufei Ma, Dionne M. Hines, Zhongyun Zhao, Julie Munakata, Beth L. Barber
Journal: Journal of Clinical Oncology (2015)

e20086 Background: Real-world evidence on the use of melanoma therapy is limited. This study was to describe the real-world treatment patterns of current melanoma therapies among patients with metastatic melanoma in the US. Methods: A retrospective cohort analysis was conducted using the IMS PharMetrics Plus claims database. Patients were included in the analysis if: ≥ 1 prescription for ipilimumab, vemurafenib, temozolomide, or dacarbazine between 1/1/2011-8/31/2013 (the date of the first use as the index date and the drug as the index drug); diagnosis of melanoma (ICD-9-CM 172.x, V10.82) and metastasis (ICD-9-CM 196.x-198.x) before the index date (pre-index); no index drug use pre-index date; continuous health plan enrollment for ≥ 6 months before and ≥ 3 months after the index date; age ≥ 18 years. Treatment duration was assessed from the index date until a gap in days supplied for > 90 days, or the end of follow-up, whichever came first. Proportion of days covered (PDC) was defined as days exposed to the index therapy divided by continuously-enrolled days between the index date and the last prescription date of the index drug. Results: 1,043 patients with metastatic melanoma were included, with a median age of 57 years (43% ≤ 55 years), and 62% male. 405 patients received the index drug of ipilimumab, 361 vemurafenib, 203 temozolomide, and 74 dacarbazine. Mean (median) treatment duration with vemurafenib, temozolomide and dacarbazine was 174 (148), 100 (59) and 64 (52) days, respectively. Mean PDC with vemurafenib, temozolomide and dacarbazine was 81%, 67% and 51%, respectively. For patients receiving ipilimumab, 58% (234/405) had the full 4 doses, 20% (79/405) had 3 doses only, 14% (57/405) had 2 doses only, and 9% (35/405) had 1 dose only for the first induction course; 4% (10/234) received re-induction, and no patients had a 3rd re-induction course of treatment. Conclusions: This study provides evidence of current treatment patterns of melanoma therapies, including newer agents, in the real-world clinical practice.
Ethnic differences in survival of elderly chronic myeloid leukemia patients in pre- and post-imatinib era in the United States.
Authors: Dipesh Uprety, Binay Kumar Shah
Journal: Journal of Clinical Oncology (2015)

7063 Background: Survival of chronic myeloid leukemia (CML) has improved since FDA approval of imatinib in May 2001. However, there is limited data on survival pattern of elderly patients. We conducted this study to evaluate ethnic differences in survival of elderly CML patients. Methods: We selected elderly CML patients ( ≥ 65 years) from the Surveillance, Epidemiology, and End Results (SEER) 18 database. We analyzed one- and five-year relative survival (RS) rates of CML patients by ethnicity during pre-imatinib (1990-2000) and post-imatinib (2001-2006) time periods. We used Z-test to compare survival rates. Results: The database comprised of 5,802 patients. Among them, 3,183 were males and 2,619 were females. Likewise, 5,073 were Caucasians and 394 were African Americans. The median age at diagnosis was 76 years. The median follow up period was 18 months (range: 1 to 60 months). The RS of the patients improved significantly in post-imatinib era as compared to pre-imatinib era (1 year: 65.6 ± 0.9 vs 59.2 ± 1.0, Z score = 4.93; 5 year: 34.6 ± 1.1 vs 22.2 ± 0. 9, Z score = 8.45). Survival rates of Caucasians improved significantly (1 year: 59.2 ± 1.1 vs 65.6 ± 1.0, Z score = 4.49; 5 year: 22.3 ± 1.0 vs 34.3 ± 1.1, Z score = 7.59) but there was no significant improvement in survival for African Americans (1 year: 58.8 ± 3.8 vs 61.1 ± 3.7, Z score = 0.49; 5 year: 21.1 ± 3.5 vs 31.1 ± 4.0, Z score = 1.61). There was no difference in survival rates of African Americans compared to Caucasians in pre-imatinib era. Conclusions: Survival rates of elderly CML patients have improved significantly in post-imatinib era. This improvement in survival rates is limited to Caucasians.
Understanding Lactatemia in Human Sepsis. Potential Impact for Early Management
Authors: Luciano Gattinoni, Francesco Vasques, Luigi Camporota, Jennifer Meessen, Federica Romitti, Iacopo Pasticci, Eleonora Duscio, Francesco Vassalli, Lui G. Forni, Didier Payen, Massimo Cressoni, Alberto Zanella, Roberto Latini, Michael Quintel, John J. Marini
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy.Objectives: To understand the relationship among central venous oxygen saturation (ScvO2), lactate, and base excess to better determine the origin of lactate.Methods: This was a post hoc analysis of baseline variables of 1,741 patients with sepsis enrolled in the multicenter trial ALBIOS (Albumin Italian Outcome Sepsis). Variables were analyzed as a function of sextiles of lactate concentration and sextiles of ScvO2. We defined the "alactic base excess," as the sum of lactate and standard base excess.Measurements and Main Results: Organ dysfunction severity scores, physiologic variables of hepatic, metabolic, cardiac, and renal function, and 90-day mortality were measured. ScvO2 was lower than 70% only in 35% of patients. Mortality, organ dysfunction scores, and lactate were highest in the first and sixth sextiles of ScvO2. Although lactate level related strongly to mortality, it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dl), as rapidly detected by a negative alactic base excess. In contrast, positive values of alactic base excess were associated with a relative reduction of fluid balance.Conclusions: Hyperlactatemia is powerfully correlated with severity of sepsis and, in established sepsis, is caused more frequently by impaired tissue oxygen use, rather than by impaired oxygen transport. Concomitant acidemia was only observed in the presence of renal dysfunction, as rapidly detected by alactic base excess. The current strategy of fluid resuscitation could be modified according to the origin of excess lactate.
STELLAR: Final updated results of a phase II trial of TTFields with chemotherapy for unresectable malignant pleural mesothelioma
Authors: G.L. Ceresoli, J.G. Aerts, R. Dziadziuszko, S. Cedres, B. Hiddinga, J.P. Van Meerbeeck, M. Mencoboni, D. Planchard, A. Chella, L. Crinò, M.J. Krzakowski, J. Madrzak, R. Ramlau, F. Grosso
Journal: Annals of Oncology (2019)

Background: Tumor Treating Fields (TTFields), an anti-mitotic, regional treatment approved for glioblastoma utilizes low intensity, alternating electric fields delivered non-invasively to the tumor using a portable medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields. Methods: The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria included ECOG PS of 0-1 and pathologically proven mesothelioma. The primary endpoint was overall survival (OS). A visual analog scale was used to assess EOCG performance status and cancer-related pain assessed until disease progression. The sample size provided 80% power with two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months compared to historical controls (Vogelzang, JCO 2003). Results: All 80 patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2 months (95% CI 12.1-25.8) versus 12.1 months in the historical control. Median OS for epithelioid patients was 21.2 months (95% CI 13.2-25.8). ECOG score was stable during the first year of follow up. Median time to deterioration in performance status was 13.1 months. Average score of pain was lower compared to baseline during the first 7 months of the treatment and was higher later on the study, with a median time to a clinical significant 33% increase in pain of 8.4 months. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Four patients (5%) had grade 3 dermatitis. Conclusions: The study met primary endpoint of significant extension of overall survival in previously untreated mesothelioma patients. TTFields was not associated with a decrease in performance status or an increase in pain for the duration of TTFields use. TTFields in combination with chemotherapy is efficacious in malignant pleural mesothelioma compared to historical data. Clinical trial identification: NCT02397928. Legal entity responsible for the study: Novocure. Funding: Novocure. Disclosure: G.L. Ceresoli, F. Grosso: Travel funds: Novocure. All other authors have declared no conflicts of interest.
THU-268-Human microfibrillar-associated protein 4 expressed in the liver and serum in alcoholic liver disease predicts liver fibrosis severity with accuracy similar to transient elastography and enhanced liver fibrosis test
Authors: Bjørn Madsen, Maja Thiele, Sönke Detlefsen, Maria Kjærgaard, Linda Sevelsted Møller, Ditlev Nytoft Rasmussen, Anders Schlosser, Uffe Holmskov, Jonel Trebicka, Grith Lykke Sorensen, Aleksander Krag
Journal: Journal of Hepatology (2019)
The Bane of “Boilerplate” Language in Research Consent Forms: Ensuring Consent Forms Promote Autonomous Authorization
Authors: Jeffrey R. Botkin
Journal: The American Journal of Bioethics (2019)

"The Bane of "Boilerplate" Language in Research Consent Forms: Ensuring Consent Forms Promote Autonomous Authorization." The American Journal of Bioethics, 19(4), pp. 83–84
SAT-234-Risk of hepatocellular carcinoma and efficacy of direct-acting antivirals in patients with concurrent hepatitis C virus
Authors: Elizabeth Harrod, Ritu Agarwal, Parissa Tabrizian, Madhavi Rayapudi, Aftab Ala, Isabel Fiel, Myron Schwartz, Douglas Dieterich, Scott Friedman, Behnam Saberi
Journal: Journal of Hepatology (2019)
Contaminated blood scandal: solicitors for victims call for hepatitis C screening programme in England and Wales
Authors: Susan Mayor
Journal: BMJ (2019)

Solicitors acting on behalf of people who received contaminated blood have urged NHS England and Public Health Wales to set up nationwide screening programmes to detect any people currently unaware that they are infected with the virus, so that they can start treatment.

The law firm Leigh Day is representing more than 300 people affected by contaminated blood as part of the infected blood inquiry,1 a UK-wide public inquiry into the use …
Blood plasma versus serum: which is right for sampling circulating membrane microvesicles in human subjects?
Authors: Ming-Lin Liu, Victoria P Werth, Kevin Jon Williams
Journal: Annals of the Rheumatic Diseases (2019)

We have read with great interest the article by Kato and colleagues regarding the ‘Apoptosis-derived membrane vesicles drive the cGAS–STING pathway and enhance type I IFN production in systemic lupus erythematosus’.1 However, we are concerned that the authors studied exclusively blood serum, that is, all blood samples from their patients with lupus and healthy controls were coagulated ex vivo before analysis.

At least three major changes can occur to the population of membrane microvesicles (MVs) during coagulation in a test tube. First, a subset of circulating MVs participate in, and become consumed by, clotting. For example, studies from our group and others indicated that over half of the total membrane MVs in blood plasma …
Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001
Authors: A.T. Shaw, G.J. Riely, Y.-J. Bang, D.-W. Kim, D.R. Camidge, B.J. Solomon, M. Varella-Garcia, A.J. Iafrate, G.I. Shapiro, T. Usari, S.C. Wang, K.D. Wilner, J.W. Clark, S.-H.I. Ou
Journal: Annals of Oncology (2019)

BackgroundIn the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001.Patients and methodsROS1 status was determined by FISH or reverse transcriptase–polymerase chain reaction. All patients received crizotinib at a starting dose of 250 mg twice daily.ResultsFifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% [95% confidence interval (CI), 58% to 83%], including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2–45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2–39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6 months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4 months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between OS and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2, per CTCAE v3.0. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment.ConclusionsThese findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup.Trial Registration NumberClinicalTrials.gov identifier NCT00585195
Are we there yet? The never-ending quest for an Epstein-Barr virus vaccine
Authors: Sandhya Sharma, Rayne H. Rouce
Journal: Journal of Clinical Investigation (2019)

The Epstein-Barr virus (EBV) is estimated to infect a large part of the population and is associated with a variety of human tumors; therefore, EBV is an important target for vaccine development. In this issue of the JCI, Rühl et al. developed a promising heterologous prime-boost vaccination strategy for EBV-associated malignancies and symptomatic primary infection. The authors show that two prime-boost regimens, using either dendritic cells or an adenovirus approach targeting nuclear antigen EBNA1 followed by a modified vaccinia virus Ankara (MVA) booster, induced significant T cell-mediated, EBV-specific immune control and Ab production. These findings suggest that administration of heterologous prime-boost vaccinations targeting EBNA1 may result in potent CD4+ and CD8+ T cell-mediated EBV immune control and may be a promising clinical approach.
THU-270-Severe alcoholic hepatitis has no influence on prognosis of variceal bleeding in patients with alcoholic cirrhosis
Authors: Petra Fischer, Andreea Fodor, Adelina Horhat, Daniela Matei, Maria Imbuzan, Ingrit Iuhasz, Oana Nicoara-Farcau, Andreea Bumbu, Zeno Sparchez, Marcel Tantau, Horia Stefanescu, Bogdan Procopet
Journal: Journal of Hepatology (2019)
PS-119-Time-varying mHAP III is the most accurate score in predicting survival in patients wit hepatocellular carcinoma undergoing trans-arterial chemoembolization
Authors: Claudia Campani, Alessandro Vitale, Sami Aburas, Gabriele Dragoni, Umberto Arena, Edoardo Giovanni Giannini, Umberto Cillo, Franco Trevisani, Fabio Marra
Journal: Journal of Hepatology (2019)