tbuckley/cabot-search huggingface dataset:
Ramucirumab (RAM) or merestinib (MER) or placebo (PL) plus gemcitabine (GEM) and cisplatin (CIS) as first-line treatment for advanced or metastatic biliary tract cancer (BTC): A randomized, double-blind, phase II study.
Authors: Juan W. Valle, Li-Yuan Bai, Rashida Orlova, Eric Van Cutsem, Jorge Adeva Alfonso, Li-Tzong Chen, Radka Obermannova, Thomas Jens Ettrich, Jen-Shi Chen, Harpreet Singh Wasan, Crystal S. Denlinger, Arndt Vogel, Aiwu Ruth He, Nathalie Bousmans, Allicia C Girvan, Wei Zhang, Richard A. Walgren, Roberto Carlesi, Do-Youn Oh
Journal: Journal of Clinical Oncology (2020)

477 Background: We assessed RAM or MER plus standard of care GEM+CIS as first-line treatment for BTC. Methods: Patients (pts) with BTC, ECOG PS 0/1, and measurable disease were randomized 2:1:2:1 to oral MER 80 mg QD, oral PL QD, IV RAM 8 mg/kg days 1 and 8 Q3W or IV PL days 1 and 8 Q3W. Pts also received up to 8 cycles IV GEM 1000 mg/m 2 + CIS 25 mg/m 2 days 1 and 8 Q3W. RAM, MER, or PL could continue until disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall survival (OS), objective response rate (ORR), and safety. PFS and hazard ratios (HRs) were compared using stratified log-rank tests and Cox regression models, respectively. NCT02711553. Results: 309 pts were randomized to RAM (106), MER (102), or pooled PL (101). More pts in the RAM (54.7%) and MER (49.0%) groups had baseline ECOG PS 1 vs PL (38.6%). Efficacy endpoints are in Table. Fewer pts received post-discontinuation systemic therapy in the RAM group (RAM 37.5%, MER 50.0%, PL 52.0%). The most common grade ≥3 treatment-emergent adverse events were: RAM vs PL: neutropenia (49.0% vs 33.0%), thrombocytopenia (34.6% vs 17.0%), and anemia (26.9% vs 19.0%); MER vs PL: neutropenia (47.1% vs 33.0%), thrombocytopenia (18.6% vs 17.0%), and alanine aminotransferase increased (10.8% vs 5.0%). Conclusions: PFS, OS, and ORR were not improved with the addition of RAM or MER to GEM+CIS. Treatment was well tolerated, with safety profiles consistent with known profiles for RAM, MER, and GEM+CIS. Translational studies are ongoing. Clinical trial information: NCT02711553 . [Table: see text]
日本人の関節リウマチにおけるACPA値に対するHLA-DRB1対立遺伝子の定量的効果: HLA-DRB1*09:01成層後のACPA値への共有エピトープの強くはない遺伝学的影響
Authors: Terao Chikashi, Ikari Katsunori, Ohmura Koichiro, Suzuki Taku, Iwamoto Takuji, Takasugi Kiyoshi, Saji Hiroo, Taniguchi Atsuo, Momohara Shigeki, Yamanaka Hisashi, Matsuda Fumihiko, Mimori Tsuneyo
Journal: Annals of the Rheumatic Diseases (2012)
Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization
Authors: Pavlo Gilchuk, Charles D. Murin, Jacob C. Milligan, Robert W. Cross, Chad E. Mire, Philipp A. Ilinykh, Kai Huang, Natalia Kuzmina, Pilar X. Altman, Sean Hui, Bronwyn M. Gunn, Aubrey L. Bryan, Edgar Davidson, Benjamin J. Doranz, Hannah L. Turner, Tanwee Alkutkar, Robin Flinko, Chiara Orlandi, Robert Carnahan, Rachel Nargi, Robin G. Bombardi, Megan E. Vodzak, Sheng Li, Adaora Okoli, Morris Ibeawuchi, Benjamin Ohiaeri, George K. Lewis, Galit Alter, Alexander Bukreyev, Erica Ollmann Saphire, Thomas W. Geisbert, Andrew B. Ward, James E. Crowe
Journal: Immunity (2020)
The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus
Authors: Lijun Kang, Yi Li, Shaohua Hu, Min Chen, Can Yang, Bing Xiang Yang, Ying Wang, Jianbo Hu, Jianbo Lai, Xiancang Ma, Jun Chen, Lili Guan, Gaohua Wang, Hong Ma, Zhongchun Liu
Journal: The Lancet Psychiatry (2020)
Evaluation of the ratio of plasma fibrinogen to platelet in resectable pancreatic cancer.
Authors: Yusuke Arakawa, Mitsuo Shimada, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yu Saito, Shinichiro Yamada, Masato Yoshikawa, Katsuki Miyazaki
Journal: Journal of Clinical Oncology (2020)

756 Background: Several prognostic factors were reported in pancreatic cancer such as neutrophil lymphocyte ratio (NLR), platelet lymphocyte ration (PLR) modified GPS. Fibrinogen platelet ratio (FPR) was reported as one of the prognostic factor of resectable gastric cancer (Surgery today 2019). In this report, the FPR was evaluated in patients with resectable pancreatic cancer. Methods: Between 2004 and 2019, one hundred and sixty-three patients in our institution with curative resection for pancreatic cancer were enrolled in this retrospective study. The cases of non-curative resection were excluded. The FPR was calculated with the preoperative plasma fibrinogen and the platelet counts. Cut-off value was decided with ROC curve. The patients were divided into high and low FPR group according to cut-off value. Results: The cut-off value of FPR was 25.51. In age, gender, BMI, operative factors including operative type, amount of blood loss and operative time, there was no significant difference between these two groups. Patients in low FPR group had significantly better overall survival (OS) rates and relapse-free survival (RFS) rates compared with high FPR group (p &lt; 0.05). On multivariate analysis, the high FPR, CA19-9 &gt; 300 U/ml and receipt of adjuvant chemotherapy were independent risk factor of post-operative recurrence. Conclusions: The FPR might be a prognostic factor of patients with resectable pancreatic cancer.
A phase III study of nivolumab (Nivo) in previously treated advanced gastric or gastric esophageal junction (G/GEJ) cancer (ATTRACTION-2): Three-year update data.
Authors: Li-Tzong Chen, Yoon-Koo Kang, Taroh Satoh, Yee Chao, Ken Kato, Hyun Cheol Chung, Jen-Shi Chen, Kei Muro, WonKi Kang, Takaki Yoshikawa, Sang Cheul Oh, Takao Tamura, Keun Wook Lee, Narikazu Boku
Journal: Journal of Clinical Oncology (2020)

383 Background: Nivo is the first immune checkpoint inhibitor (ICI) to show efficacy and tolerability in G/GEJ cancer patients refractory to or intolerant of standard chemotherapy. Although Nivo has demonstrated durable efficacy in several cancer types, no long-term efficacy data in G/GEJ cancer has been reported to date. Here, we report the 3-year survival data of Nivo in G/GEJ cancer. Methods: A total of 493 patients with unresectable advanced or recurrent G/GEJ cancer after the failure of two or more chemotherapy regimens were randomized in a 2:1 ratio to receive 3 mg/kg Nivo (N = 330) or placebo (N = 163) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Updated results of the efficacy and safety were based on ≥ 3 years of follow-up after last patient enrollment. In subgroup analysis, we evaluated OS by BOR and incidence of select treatment-related adverse events (TRAEs). Results: As of data cut-off in February 2019, 3 years after last patient enrollment, the hazard ratios of OS and PFS in the Nivo group compared with the placebo group remained 0.62 and 0.60, respectively. The 36-month OS rates of Nivo and placebo were 5.6% and 1.2 % and the 36-month PFS rates were 2.4% and 0%, respectively. In the OS subgroup analysis by BOR, the median OS and 3-year OS rate in CR/PR patients with Nivo were 26.7 months and 35.5%, respectively. The incidence rate and severity of TRAEs were comparable with those of the 2-year cut-off. In the OS subgroup analysis based on the presence or absence of select TRAEs, the hazard ratio in patients with select TRAEs was 0.46 compared to those without select TRAEs. We are analyzing the baseline characteristics that are associated with long-term survival with Nivo. Conclusions: Nivo showed durable efficacy and a good safety profile on long-term follow-up in heavily pretreated G/GEJ cancer patients. Clinical trial information: NCT02267343.
Improvement of Cardiovascular Functional Reserve After Kidney Transplant—Has the CAPER Been Solved?
Authors: George L. Bakris, Michelle A. Josephson
Journal: JAMA Cardiology (2020)

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Impact of race on incidence and survival from colorectal cancer in young adults in the United States.
Authors: Dhruvika Mukhija, Sajan Nagpal
Journal: Journal of Clinical Oncology (2020)

62 Background: Multiple studies have reported an increasing incidence of colorectal cancer (CRC) in young( &lt; 45 years)adults.However, the impact of race on the incidence, tumor location and survival in adults &lt; 45 years with CRC has not been explored. Methods: Using Surveillance,Epidemiology and End Results database,we identified patients with CRC and abstracted data on patient demographics,tumor location and survival between 1973-2014, and compared these variables in patients 18-44 years with those &gt; 45 years. Cases where CRC was not the first/only malignancy were excluded.Categorical variables were compared using the Chi-square test and overall survival was analyzed using Kaplan-Meier method. Results: Overall, 453,019 patients were included (27, 352 &lt; 45,and 425,667 &gt;45 years). 81.7% among those &gt; 45 years were caucasian, as compared to 74.3% &lt; 45 years of age. Among those &lt; 45, 14.3% were black, 10.3% were Asian/Pacific Islander (API) and 1.1% were American Indian/Alaska Native (compared to 10.1%, 7.5% and 0.6% respective in adults &gt; 45) (p &lt; 0.0001*) (Table). 73.1% of those &lt; 45 had left sided disease (descending, sigmoid colon and rectum) as compared to 60.1% in those &gt; 45 (p &lt; 0.0001*).Survival was poorer for non-white patients (black, API and AI) (94 months, 95%CI 90-100) as compared to white patients (153 months, 95%CI 145-161) overall, and individually for the &lt; 45 and &gt;45 years subgroups as well. Conclusions: Racial distribution in patients with CRC differs significantly among patients &lt; 45 as compared to older adults,with incidence in young American Indian/Alaska Natives approaching 2 times that of older adults,and 1.5 times in young Blacks and Asian/Pacific Islanders.Non-white races have poorer survival across all age groups.With rates of CRC rising sharply in young adults, underlying reasons for these differences require further investigation to better channelize efforts for education and screening. [Table: see text]
Clinical characteristics of nivolumab-induced radiation recall pneumonitis in patients with non-small cell lung cancer: A multicenter real-world analysis of 669 patients.
Authors: Tadasuke Shimokawaji, Shoko Narita, Tomoyuki Naito, Hibiki Udagawa, Koichi Goto, Taichi Miyawaki, Nobuaki Mamesaya, Kazuhisa Nakashima, Hirotsugu Kenmotsu, Terufumi Kato, Taiki Hakozaki, Yusuke Okuma, Masaki Nakamura, Yuko Nakayama, Hirokazu Watanabe, Masahiko Kusumoto, Yuichiro Ohe, Hidehito Horinouchi
Journal: Journal of Clinical Oncology (2020)

88 Background: Immune checkpoint inhibitors can cause immune-related pneumonitis in lung cancer patients. Some of those patients with history of previous thoracic radiation therapy (TRT) are reported to show radiation recall pneumonitis (RRP) pattern. In this multicenter retrospective study, we analyzed the patient background and clinical characteristics of RRP. Methods: Medical records of non-small cell lung cancer patients, who received nivolumab between December 2015 and March 2017, were retrospectively reviewed. Incidence of pneumonitis, and incidence, risk factors and clinical characteristics of RRP were analyzed at 5 institutions. Person’s chi-square test (age, sex, smoking history, performance status at the start of nivolumab treatment, background lung disease, history of previous radiation pneumonitis, total dose, volume receiving more than 20Gy, 30Gy, mean lung dose of TRT, and duration after TRT) was conducted to identify potential risk factors of RRP. RRP was defined as fibrosis or consolidation occurring in the previous TRT field, and imaging analysis was conducted by two individual radiologists. Results: A total of 669 patients were evaluated, and the incidences of all-grade and ≥ grade 3 pneumonitis were 8.8% (59/669) and 6.2% (18/669), respectively. Incidence of RRP was 5.4% (14/257) among patients with history of previous TRT. There were no significant risk factors for RRP. Although we did not find significant difference between the severity of RRP pattern and other radiological patterns of pneumonitis, patients with RRP showed better outcome. All patients recovered from RRP without no exacerbation or death, compared to 9.3% of exacerbation or death in other patterns of pneumonitis. Conclusions: Incidence of RRP was 5.4% among patients with history of previous TRT, although there were no significant risk factors of RRP. Patients with RRP pattern showed relatively better outcome.
A phase II study of trifluridine/tipiracil, irinotecan, and bevacizumab in pretreated metastatic colorectal cancer (TABAsCO).
Authors: Medhavi Gupta, Christos Fountzilas, Namrata Vijayvergia, Kristopher Attwood, Howard S. Hochster, Sarbajit Mukherjee, Renuka V. Iyer, Patrick McKay Boland
Journal: Journal of Clinical Oncology (2020)

TPS275 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in US. The majority of US patients (pts) receive first-line therapy (Rx) with FOLFOX [Folinic acid (FA), 5-fluorouracil (5-FU) and oxaliplatin (Ox)] + a biologic, making FOLFIRI [FA+ 5-FU+ irinotecan (Iri)] + bevacizumab (Bev) a common second-line Rx. This regimen has a median progression-free survival (PFS) of approximately 6 months (mo) and overall survival (OS) of 12 mo. Further gains are desperately needed. Trifluridine/tipiracil (FTD/TPI) is an oral combination Rx of a thymidine-based nucleoside analogue, FTD, and a phosphorylase inhibitor, TPI. FTD/TPI has a distinct mechanism of action from 5-FU and in preclinical models can overcome 5-FU resistance via DNA incorporation, base excision repair pathway and glycosylation responses to DNA damage. Further, there is an additive effect in combination with Iri. FTD/TPI was FDA approved for use in refractory metastatic CRC (mCRC) based on phase III RECOURSE trial. Phase I data showed combination of FTD/TPI, Iri and Bev to be safe, and an efficacy signal was seen in dose-expansion cohort (NCT01916447). A 12.5% response rate, 83.4 % disease control rate and PFS of 7.9 mo was achieved. As this study largely assessed refractory pts, one might expect a greater efficacy in Iri naïve pts. To test this hypothesis, we are conducting a multi-center phase II study of FTD/TPI, Iri and Bev as second-line Rx in mCRC pts. Methods: Eligible pts have mCRC and received first-line Ox based Rx. Rx to be given in 28-day cycles: Iri (180 mg/m 2 ) and Bev (5 mg/kg) on D1 &amp; 15, and FTD/TPI (25 mg/m 2 ) twice daily on D2-6 &amp; 16-20. Response assessment via CT/MRI to be done q8 wks (RECIST 1.1). Rx to continue until disease progression or unacceptable toxicity. The primary objective is to estimate PFS. Secondary objectives include ORR, OS, and safety. Final analysis to be done either 12 mo after enrollment of the final pt or once all pts have progression, whichever occurs earlier. A total of 40 pts to be accrued, and enrollment to start in January 2020. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Taiho Oncology, Inc.
Distinct Pathological Pathways in Patients With Heart Failure and Diabetes
Authors: Jasper Tromp, Adriaan A. Voors, Abhinav Sharma, João P. Ferreira, Wouter Ouwerkerk, Hans L. Hillege, Karla A. Gomez, Kenneth Dickstein, Stefan D. Anker, Marco Metra, Chim C. Lang, Leong L. Ng, Pim van der Harst, Dirk J. van Veldhuisen, Peter van der Meer, Carolyn S.P. Lam, Faiez Zannad, Iziah E. Sama
Journal: JACC Heart Failure (2020)
Vascular endothelial growth factor (VEGF)-D and clinical outcomes in metastatic colorectal cancer (mCRC) patients (pts) treated with second-line FOLFIRI plus bevacizumab (Bev): A biomarker study of the WJOG 6210G trial.
Authors: Naoki Izawa, Kohei Shitara, Toshiki Masuishi, Tadamichi Denda, Kentaro Yamazaki, Toshikazu Moriwaki, Hiroyuki Okuda, Chihiro Kondoh, Tomohiro Nishina, Akitaka Makiyama, Hideo Baba, Hironori Yamaguchi, Masato Nakamura, Yu Sunakawa, Kohei Akiyoshi, Mikio Sato, Kimio Yonesaka, Takayuki Yoshino, Takeharu Yamanaka, Kei Muro
Journal: Journal of Clinical Oncology (2020)

226 Background: The WJOG 6210G trial demonstrated a similar efficacy between FOLFIRI plus Bev and FOLFIRI plus panitumumab (Pani) at 2nd-line treatment in pts with KRAS exon2 wild-type mCRC (Shitara K, et al, Cancer Sci 2016). Recently, angiogenesis biomarker studies of clinical trials have identified VEGF-D as a potential predictor for angiogenesis inhibitors in mCRC. We evaluated whether VEGF-D level are associated with clinical outcomes in the WJOG 6210G trial. Methods: Plasma samples which were collected at pre-treatment were analyzed. VEGF-D level in plasma was measured by means of magnetic bead panel (G &amp; G SCIENCE CO., LTD.). The correlations of VEGF-D level with progression-free survival (PFS) and overall survival (OS) were evaluated by cox regression analyses. Results: Ninety-nine pts were evaluable for VEGF-D level (Bev, n = 51; Pani, n = 48) among 121 pts enrolled in the WJOG6210G. The median VEGF-D level was 441 pg/ml (range 60-1570). VEGF-D level was not affected by the period from last administration of 1st-line Bev to start of 2nd-line treatment. When the median VEGF-D level was adopted as cut-off value, pts with high VEGF-D achieved a shorter PFS and OS than pts with low VEGF-D in the Bev arm [HR: 0.58 (95%CI 0.32-1.07), p = 0.08; HR: 0.62 (95%CI 0.34-1.11), p = 0.10]. In pts with high VEGF-D, the Bev arm tended to have a shorter OS and PFS compared to Pani arm [median: 12.4 m vs. 17.5 m, HR: 1.58 (95%CI 0.87-2.88); median: 4.7 m vs. 5.5 m, HR: 1.31 (95%CI 0.72-2.40)]; whereas, comparable OS and PFS in pts with low VEGF-D [median: 18.9 m vs. 16.5 m, HR: 1.08 (95%CI 0.59-2.01); median: 5.9 m vs. 7.2 m, HR: 1.10 (95%CI 0.62-1.99)]. OS was stratified by VEGF-D level quartile, then OS of Bev arm in each quartile was compared with that of Pani arm (Table). Clinical trial information: UMIN000031621. Conclusions: Our study suggests clinically meaningful association between VEGF-D level and clinical outcomes in mCRC pts treated with 2nd-line FOLFIRI plus Bev. [Table: see text]
Predicting Pneumonia in Chronic Obstructive Pulmonary Disease. Have We Unraveled the Network of Risks?
Authors: Mark T. Dransfield, Dave Singh
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Have We Unraveled the Network of Risks?Inhaled corticosteroids (ICS) reduce exacerbation rates in patients with chronic obstructive pulmonary disease (COPD) but may also cause adverse effects, including pneumonia (1, 2).Blood eosinophil counts can predict the clinical response to ICS and ,100 eosinophils/ml is associated with a low probability of a reduction in exacerbation rates (3).Based in part on these data, the use of ICS in clinical practice is becoming more personalized, weighing the possibility of benefit (using exacerbation history and blood eosinophil counts) against the risk of adverse events, including pneumonia (4, 5).In this issue of the Journal, Martinez-Garcia and colleagues (pp.1078-1085) report the relationships between pneumonia risk and ICS use, blood eosinophil counts, and chronic bacterial infection (CBI) of the airways (assessed using sputum samples) from a cohort of 201 patients with COPD followed for a median of 84 months (6).Previous studies have shown that pneumonia risk factors in COPD include ICS use, older age, lower FEV 1 , lower body mass index, and previous pneumonia (7-9).An important novel aspect of this study is that bacterial infection data is included in the analysis of pneumonia risk.Bacterial isolates were detected in 42.3% of patients on at least one occasion, whereas CBI was present in 22.4%.Univariate analysis showed that older age, lower FEV 1 , presence of bronchiectasis, exacerbation rates, and ,100 eosinophils/ml were associated with CBI.These risk factors were also associated with pneumonia risk, as was CBI and ICS treatment.A multivariate Cox proportional hazard regression model showed that age, FEV 1 , CBI, and ,100 eosinophils/ml were all independently associated with pneumonia.Of note, ICS use itself was not associated with pneumonia in the overall population, although ICS further increased the risk of pneumonia in those with CBI and ,100 eosinophils/ml.Few studies of pneumonia in COPD have included blood eosinophil counts as a risk factor, mostly showing either a weak or no association (3, 10).Martinez-Garcia and colleagues also found that higher eosinophil thresholds (e.g., ,150 or ,300 cells/ml) were not associated with pneumonia risk, but very low eosinophil counts (,100 cells/ml) were associated with pneumonia, and this was the most important risk factor in the adjusted Cox regression model, ahead of age and FEV 1 (6).This is an observational study, in contrast to previous analyses of eosinophils and pneumonia risk that were based on data from randomized controlled trials (RCTs) (3, 10), and differences in study design or population characteristics may explain the varying results.Also, the way that pneumonia was defined varied, and even when chest radiographs