tbuckley/cabot-search huggingface dataset:
Intraoperative electrochemotherapy in locally advanced pancreatic cancer: Results and impact on quality of life. a single center experience.
Authors: Mariacristina Di Marco, Claudio Ricci, Riccardo Carloni, Elisa Grassi, Stefania De Lorenzo, Andrea Palloni, Francesca Abbati, Elisa Andrini, Alessandro Di Federico, Angela Dalia Ricci, Carlo Ingaldi, Carla Serra, Laura Alberici, Emilio De Raffele, Alessandra Guido, Francesco Minni, Alessandro Rizzo, Giovanni Brandi, Maria A. Pantaleo, Riccardo Casadei
Journal: Journal of Clinical Oncology (2020)

e16731 Background: Locally advanced pancreatic cancer (LAPC) is usually treated with chemoradiotherapy with poor results, thus additional therapies have been proposed. Of the latter, electrochemotherapy (ECT) represents a non-thermal ablation method, which combines the administration of chemotherapeutic drugs with permeabilizing electric pulses for cell membrane electroporation. The present study is the first to assess the short and long-term results, and the quality of life of the patients who underwent ECT for LAPC. Methods: Observational study of patients affected by LAPC who underwent intraoperative ECT after chemoradiotherapy. The inclusion criteria were: 1- patients with LAPC (defined according to the National Comprehensive Cancer Network 2019), 2- previous chemoradiotherapy and 3- absence of disease progression at restaging. Data at diagnosis and at restaging were collected for each patient. The Quality of life was evaluated using the Euro Quality of Life Group Association Questionnaire (EQ-5D-5L). The questionnaire was administered to all patients before and after ECT. Results: From May 25, 2018 to November 26, 2019 five patients underwent ECT: in 4 cases, the tumors were located in the head and, in one, in the body of the pancreas. Preoperative chemotherapy consisted mainly of 6 cycles of modified folfirinox, while the radiotherapy consisted of 54 Gy (27 fractions). At restaging, the serum value of CA 19-9 and tumor size were reduced; however, the vascular involvement did not change. No downstaging was recorded. Intravenous bleomycin 15,000IU/m2 was given as a bolus, the ECT procedure was performed using at least 4 needles with a mean duration time of 27 minutes, (range 15-40). No postoperative mortality or major complications were reported. The mean length of stay was 8 days (range 5-14). Four patients were alive and well at the end of the study while one patient died from disease progression. The mean follow-up was 20.8 months (range 9-34) from diagnosis and 9.4 months (range 2-19) from ECT. The quality of life was good (EQ-5D-5L scale &gt; 50 in all cases) and there was improvement in pain/discomfort with respect to the pre-treatment period in 3 out of 5 patients. Conclusions: Electrochemotherapy can be considered a simple, feasible and safe palliative additional treatment in LAPC without progression after chemoradiotherapy, and it seems to allow a good quality of life and pain improvement.
影响哮喘儿童药物吸入相关因素的评价
Authors: 王艳霞, 张风兰
Journal: BMJ (2006)

喘吸入疗法对儿童有一定难度,错误使用率高.本研究对常用吸入疗法中最难掌握的2种方法进行评价. 一、对象与方法 78例患儿均为本哮喘中心2004年8月至2005年6月间诊断的哮喘儿童,诊断符合文献[1].治疗中采用定量手控气雾剂吸入法(pMDI)45例,男27例,女18例,年龄6～13岁;采用干粉吸入法(DPI)33例,男16例,女17例,年龄6～12岁.
Association of gene expression with clinical outcomes in patients with renal cell carcinoma treated with pembrolizumab in KEYNOTE-427.
Authors: David F. McDermott, Jae-Lyun Lee, Frede Donskov, Scott S. Tykodi, Georg A. Bjarnason, James M. G. Larkin, Rustem Gafanov, Mark D. Kochenderfer, Jahangeer Malik, Alexandr Poprach, Sabina Signoretti, Razvan Cristescu, Raluca Andreia Predoiu, Andrey Loboda, Yiwei Zhang, Qing Zhao, Alexandra Snyder, Charles Schloss, Rodolfo F. Perini, Michael B. Atkins
Journal: Journal of Clinical Oncology (2020)

5024 Background: We assessed the association of baseline RNA-sequencing–based gene expression signatures and DNA alterations with response or resistance to pembrolizumab in patients with advanced renal cell carcinoma in cohorts A (clear cell; n = 110) and B (non-clear cell; n = 165) of the phase 2 KEYNOTE-427 study (NCT02853344). Methods: Using RNA-sequencing, we analyzed the association of gene expression signatures (18-gene T-cell–inflamed gene expression profile [GEP]; 10 non–T-cell–inflamed GEP canonical signatures [angiogenesis, gMDSC, glycolysis, hypoxia, mMDSC, MYC, proliferation, RAS, stromal/EMT/TGFβ, WNT]) quantifying tumor microenvironment elements (TME) with objective response rate (ORR) and progression-free survival (PFS). Canonical signatures were derived from 2 databases (TCGA, Moffit) using an algorithm that included genes based on their correlation to reference signatures in the literature. Signature definitions were finalized before linking to the clinical data, and significance was prespecified at 0.10 given the potential for limited power. Canonical signatures were analyzed through regression testing of response for association with consensus signatures after adjusting for T-cell–inflamed GEP and International Metastatic RCC Database Consortium scores in the model. P values were adjusted for multiplicity. Using whole exome sequencing, we also summarized the association of renal cell carcinoma driver gene mutations with ORR. Clinical data cutoff: Jan 30, 2019. Results: Patient characteristics for this analysis were comparable to the overall population. In cohort A, T-cell–inflamed GEP (n = 78) was statistically significantly associated with a better ORR ( P = 0.021; AUROC = 0.65) but not PFS ( P = 0.116). No other TME canonical signatures showed a correlation with ORR or PFS. ORR was estimated for mutations (Table). Conclusions: RNA-sequencing–based, T-cell–inflamed GEP was associated with ORR in patients with clear cell renal cell carcinoma receiving first-line pembrolizumab. Precision was limited by sample size for estimating ORR by specific gene mutation status. Evaluation of tissue-based biomarkers in larger studies are planned. Biomarker analyses from patients in cohort B will also be presented. Clinical trial information: NCT02853344 . [Table: see text]
The model of training the trainers in community general practice
Authors: Qian Chen, Tian-hao Wang, Jie Gu, Yuan Zhang, Shan-zhu Zhu, Hong-chang Wang
Journal: BMJ (2013)

Objective
To evaluate a normative and systematic training mode for teachers of community general practice.


Methods
A total of 16 general practice teachers, who came from Fenglin community health service centre in Shanghai, participated three-stage training mode during March 2011 to February 2012. The clinical competence evaluation and questionnaire survey were conducted before and after training. Fifty trainees trained by the teachers also received clinical competence evaluation.


Results
After the three-stage training, the test score in medical knowledge, physical examination and clinical skills of the teachers did not change significantly(P=0.794, 0.674 and 0.326). The self assessment questionnaire survey of general practice teachers indicated a significant increase, especially in practice capability (t=-2.840, P=0.015) and overall quality (t=-3.017, P=0.011). After training by the teachers, the medical knowledge (t=-9.200, P=0.000), physical examination (t=-9.947, P=0.000) and clinical skills (t=-14.828, P=0.000) of 50 trainees increased markedly.


Conclusions
Differed from conventional training courses, the three-stage training enhances teaching ability and overall quality of community general practice teachers, and provides a effective training model.


Key words: 
General practitioner; Teacher training
Comparison between PSI and CURB-65 score for the prognostic assessment of elderly community acquired pneumonia
Authors: Xingjing Li, Peng Wang, Fang Shen
Journal: BMJ (2014)

Pneumonia severity score (PSI) and CURB-65 were used to evaluate the medical records of 218 elderly inpatients with community acquired pneumonia (CAP) at our hospital. The comparisons of PSI and CURB-65 were made. According to PSI, there were 21, 82, 105, 11 patients in grades Ⅱ-Ⅴ and the fatality rate were 0.0%, 1.2%, 12.4%, 5/11 respectively. There were 157, 48, 11, 1 and 1 patients with CURB-65 score of 1-5 and the fatality rate were 1.3%, 14.6%, 8/11 , 1/1, 1/1 respectively. The results indicated that both PSI and CURB-65 could be used for evaluating the prognosis of elder CAP. The former offered an overall evaluation of disease, but it was too complicated. The later was easy to use but it could underestimate the condition of elder CAP.


Key words: 
Community-acquired pneumonia; Assessment
卡维地洛联用血管紧张素转换酶抑制剂及利尿剂治疗高原心脏病疗效观察
Authors: 李高元, 刘争建, 石焕青, 王立志, 周军
Journal: BMJ (2010)

高原心脏病(highaltitude heart disease,HAHD)是由于长期慢性缺氧致肺动脉壁增厚、肺动脉压力增高等因素使右心室负荷增加,导致右心室增大、右心衰竭或以右心衰竭为主的全心衰竭[1].本研究旨在观察卡维地洛联用血管紧张素转换酶抑制剂(ACEI)、利尿剂治疗HAHD心功能Ⅱ-Ⅳ级患者的疗效。
Cytokines as a prognostic biomarker of overall survival in pancreatic cancer.
Authors: Harold Nathan Choa Tan, Rogelio Nona Velasco, Michael Ducusin San Juan, Gerardo H. Cornelio
Journal: Journal of Clinical Oncology (2020)

e16753 Background: Pancreatic cancer is an aggressive malignancy with a dismal 5-year survival rate of only 9%. Novel biomarkers are urgently needed to improve the survival outcomes of patients with this dreaded disease. Cytokines serve a key role in tumor development and metastasis in pancreatic cancer, with each cytokine demonstrating unique functionality in the tumor microenvironment. This meta-analysis examined the role of cytokines in prognosticating overall survival (OS) of pancreatic cancer patients. Methods: Relevant literature were identified via electronic search of PubMed, EMBASE, Google Scholar and Cochrane Library databases up to January 1, 2020. Employing Review Manager 5.3, pooled hazard ratios and 95% confidence intervals were computed. Results: A total of 18 studies comprising 1920 patients were included. Pooled analysis showed worse OS among patients with high T-helper 1 (Th1) cytokines, with a hazard ratio of 1.48 (95% CI 1.27-1.74, p &lt; 0.00001). High T-helper 2 (Th2) cytokines also demonstrated significant association with poor OS, with a hazard ratio of 1.62 (95% CI 1.12–2.34, p = 0.01). In terms of individual cytokines, high IL-6 correlated with inferior OS, with a hazard ratio of 2.73 (95% CI 2.18-3.43, p &lt; 0.00001). Similarly, high IL-12 were linked with worse OS, with a hazard ratio of 1.85 (95% CI 1.26-2.72, p = 0.002). Other individual cytokines were not significantly associated with OS. Conclusions: Cytokines show promise as a prognostic biomarker in pancreatic cancer. Th1 and Th2 cytokines portend worse overall survival outcomes. In particular, high levels of IL-6 and IL-12 can potentially prognosticate patients with poor overall survival. Further prospective studies are encouraged to delineate the role of cytokines in mediating treatment outcomes in this deadly disease.
A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer.
Authors: Quincy S. Chu, Derek J. Jonker, Diane M. Provencher, Wilson H. Miller, Nathaniel Bouganim, Anthony Frank Shields, Geoffrey Shapiro, Michael B. Sawyer, Stephanie Lheureux, Vanessa Samouelian, Walter H. Gotlieb, Khashayar Esfahani, Sara L. Zaknoen, Patricia S Smith, Joel Owen, Caroline Fortier, John R. Stille, Darcy Vincett, Amit M. Oza
Journal: Journal of Clinical Oncology (2020)

3581 Background: LY2880070 (LY) is an oral, selective competitive inhibitor of checkpoint kinase 1 (Chk1). Chk1 inhibitors are known to increase the anti-tumor efficacy of agents such as gemcitabine (GEM), which induce replication stress. Synergy between these two agents has been applied to the clinical setting. Methods: This two-part, open-label multi-center study explores the safety, pharmacokinetics (PK), and anti-tumor activity of LY in patients with advanced or metastatic cancers. The primary objective of this study was to determine the maximum tolerated dose (MTD) for multiple escalating oral doses of LY in combination with GEM. Secondary objectives were to: 1) Characterize the dose-limiting toxicities (DLTs) and overall safety profile for LY; 2) Evaluate the PK of LY; and 3) Evaluate the anti-tumor activity of LY. Patients received LY in a variety of different dose regimens, in combination with GEM (50 to 800 mg/m 2 ) on days 1, 8, and 15 (optional) of a 21-day cycle. Results: The combination of LY with GEM required lower doses of both LY (vs 200 mg BID monotherapy RP2D dose) and GEM (vs approved doses). The dose levels explored ranged from LY:GEM of 10 mg QD:800 mg/m 2 to 50 mg BID:100 mg/m 2 . BID dosing of LY was implemented in order to maximize the total daily dose and avoid the adverse events that appeared to correlate with C max . Treatment-emergent adverse events in &gt; 40% of patients included vomiting, nausea, and fatigue. DLTs included reduced platelet count (Gr2), fatigue (Gr3), diarrhea (Gr3), and thrombocytopenia (x2, Gr2). The t 1/2 of LY was ~ 5 h, and was not significantly affected by combination with GEM. Two patients had a best overall response of SD for a duration of ≥ 6 cycles, and a confirmed PR was observed in an ovarian cancer patient who had failed multiple regimens. Conclusions: LY was tolerated in combination with lower dose GEM. The toxicity profile can be modulated by changing the dosing frequency from QD to BID while administering the same daily dose. LY may be good candidate for combination therapy with DNA damaging agents. Clinical trial information: NCT02632448 .
Camrelizumab plus famitinib malate in patients with advanced renal cell cancer and unresectable urothelial carcinoma: A multicenter, open-label, single-arm, phase II trial.
Authors: Yuan-Yuan Qu, Hongqian Guo, Hong Luo, Qing Zou, Ninazeng Xing, Zhongquan Sun, Xuepei Zhang, Shujie Xia, Chaohong He, Hailiang Zhang, Jinling Cai, Xiao Zhang, Quanren Wang, Dingwei Ye
Journal: Journal of Clinical Oncology (2020)

5085 Background: Camrelizumab (SHR-1210) is a humanised anti-PD-1 antibody. Famitinib malate is a tyrosine kinase inhibitor (TKI) against VEGFR-2, PDGFR, c-kit, and FGFR. This is an ongoing, open label, multi-center Phase II study to assess the preliminary efficacy and safety of camrelizumab in combination with famitinib malate in patients (pts) with genitourinary cancers and gynecologic cancers. Here we just report genitourinary cancers results. Methods: Eligible pts were aged 18 or older, who had advanced clear-cell renal-cell carcinoma with their primary tumour resected or unresectable urothelial carcinoma, had an ECOG performance status of 0-1and measurable disease. Previous system treatments were allowed (excluding prior PD-1/PD-L1 inhibitors or famitinib treatment). Famitinib 20 mg was administered orally once daily with SHR-1210 200 mg given intravenously every 3 weeks. We assessed antitumour activity and safety in all pts who received at least one dose treatment. The primary end point was objective response rate (ORR) per RECIST v1.1. Results: From 23 Jan 2019 to 24 Jun2019, 35 pts were enrolled (25 with RCC, 10 with UC). Median previous treatment line was 1 (range, 1-4), and 50.0% of pts had received ≥2 prior therapies in RCC, all pts received one or more-line therapies in UC. At the data cut-off date (Dec 31, 2019), after at least 6 months follow-up, 22 (63%) pts were still receiving study treatment. The most common reason for discontinuing treatments was disease progression (n = 10). 16 pts achieved a confirmed response, all were partial response, with 8 additional &gt; 24 weeks stable disease. the ORR was 52.0% (13/25, 95% CI 31.3% to 72.2%) in RCC and 30.0% (3/10) in UC, the disease control rate was 84.0% (21/25) in RCC and 70.0% in UC. 13/16 confirmed PR pts were still on treatment, the median duration of response is not reached. The most common grade 3-4 treatment-related AEs (TRAEs) were hypertension (17.1%), proteinuria (11.4%), platelet count decreased (8.6%), hand-foot syndrome (8.6%) and anemia (5.7%). Immune-related adverse events were observed in 7 pts (20%) of 35 pts, 1 pt (2.9%) with grade 3 enteritis. Conclusions: The camrelizumab with famitinib combination appeared to show encouraging activity in pts with heavy-treated RCC and UC, and the safety profile of the combination seemed to be manageable and consistent with that of each drug alone. This combination represented a novel potential treatment option for these settings and warranted further investigation. Clinical trial information: NCT03827837 .
Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism
Authors: Qingxin Zhou, Meihua Lin, Xing Feng, Fei Ma, Yuekun Zhu, Xing Liu, Chao Qu, Hong Sui, Bei Sun, Anlong Zhu, Heng Zhang, He Huang, Zhi Gao, Yongxiang Zhao, Jiangyun Sun, Yuxian Bai, Junfei Jin, Xuehui Hong, Chang Zou, Zhiyong Zhang
Journal: The Journal of Experimental Medicine (2020)

CDC-like kinase 3 (CLK3) is a dual specificity kinase that functions on substrates containing serine/threonine and tyrosine. But its role in human cancer remains unknown. Herein, we demonstrated that CLK3 was significantly up-regulated in cholangiocarcinoma (CCA) and identified a recurrent Q607R somatic substitution that represented a gain-of-function mutation in the CLK3 kinase domain. Gene ontology term enrichment suggested that high CLK3 expression in CCA patients mainly was associated with nucleotide metabolism reprogramming, which was further confirmed by comparing metabolic profiling of CCA cells. CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes. Notably, the CCA-associated CLK3-Q607R mutant induced USP13-Y708 phosphorylation and enhanced the activity of c-Myc. In turn, c-Myc transcriptionally up-regulated CLK3. Finally, we identified tacrine hydrochloride as a potential drug to inhibit aberrant CLK3-induced CCA. These findings demonstrate that CLK3 plays a crucial role in CCA purine metabolism, suggesting a potential therapeutic utility.
Survey on knowledge of chronic heart failure and influencing factors in general practitioners in Beijing
Authors: Tao Xiao, Zhaoxia Yin, Shu Cai, Yang Chen
Journal: BMJ (2014)

Objective
To investigate the knowledge of chronic heart failure (CHF) and influencing factors in general practitioners (GP) in Beijing.


Methods
A self-designed questionnaire contained total 28 items, including basic knowledge of CHF, non-drug management, drug management and other management; clinical cases were used to test clinical ability in 7 items. The questionnaire survey was conducted among GPs who participated in continuing education courses from 16 counties/districts in Beijing during January to June 2013.


Results
Total 720 questionnaires were distributed and 657 valid questionnaires were returned with a recovery rate of 91.3%. Total scores was 60.6. Scores of basic knowledge, non-drug management, drug management and other management was 63.1, 76.9, 44.0 and 56.9, respectively. There were statistical differences in scores of basic knowledge, non-drug management, drug management and other management between GPs with different diploma (F value: 36.8, 5.8, 21.6, 12.2, respectively; P 0.05).


Conclusions
The knowledge of CHF is less desirable in GPs of Beijing, so that measures should be taken to improve the GP's knowledge of CHF.


Key words: 
General practitioners; Heart failure; Questionnaires
Survey on knowledge, attitude and practice about hypertention in elderly patients from communities of Shanghai Xuhui District
Authors: Jie Gu, Xiang-jie Zhang, Tian-hao Wang, Yuan Zhang, Qian Chen
Journal: BMJ (2012)

Objective To survey on the knowledge,attitude and practice about hypertention in elderly patients and its relation to blood pressure control.Methods A sampling survey on the knowledge,atitude and practice about hypertention were carried out in a target population of 47 572 elderly hypertensive patients from 5 communities in Xuhui District of Shanghai during May 2011 to July 2011.Total 3800 questionairres were distributed and 3328 responded with a response rate of 87.5％.Results Among 3328 responders,3036 were aged above 65 years with a mean age of (76 ±7) years and 43.3％ were males.The rates of knowledge about  were 88.5％-97.8％.General practitioners in out-patient service were the major source of knowledge.Raults revealed that 81.9％ had received health education before;81.8％ requied a regular health education; 67.2％ had self-tested blood pressure weekly; 89.6％ controlled salt intake; 66.8％ attended outdoor activities weekly with (5.6 ±2.1) times a week and (45 ±28) min each time.The blood pressure control rate in uncomplicated hypertensive patients was higher than those complicated with diabetes,coronary heart disease or stroke (62.3 ％ vs.17.0％,P ＜ 0.01).Knowing high blood pressure was related to salt intake (OR =3.364,P ＜ 0.01),hoping a regular health education about hypertension (OR =1.718,P ＜ 0.01) were factors contributing to blood pressure control in uncomplicated hypertensive patients; while self-testing blood pressure once or twice a month(OR =2.572,P ＜ 0.01)was contributing factor to blood pressure control in complicated hypertensive patients.Conclusions Elderly hypertensive patients from communities in Shanghai have enough knowledge,positive attitude but lack practices.General practitioners should carry out personalized and stronger health education focued on behavioral changes for those patients.

Key words: 
Hypertension; Elderly; Questionnaires