tbuckley/cabot-search huggingface dataset:
NBI system versus conventional endoscopy in diagnosis of colorectal adenomas: a systematic review
Authors: Xi-feng Jin, Tong-hai Chai, Chun-an Liu, Huan-ming Zhou, Juan Fang
Journal: BMJ (2009)

Objective To evaluate the validity of narrow-band imaging (NBI) system in detection of colorectal adenoma, as compared to that of endoscopy of the colon and rectum, in a systematic review. Methods Relevant literatures were retrieved from Medline (January 1966 to October 2008), OVID (January 1996 to October 2008), EMBASE (January 1980 to October 2008), Coehrane Library (Issue 3, 2008) and Chinese Biological Medicine Disk (CBM disk, January 1997 to October 2008). Quality of the literatures retrieved was assessed based on the Cochrane Reviewers' Handbook and Jadad's score. RevMan version 4. 2 software was used for meta-analysis. Results Seven randomized clinical trials (2838 patients) were included in the study. Compared with white-light colonoscopy, no significant difference was observed in terms of adenoma detection rate (OR 1.18, 95% CI 1.00-1.39, P=0.06) by NBI system, which could significantly improve total number of detection for fiat lesions of the colon and rectum (pooled WMD 0.14, 95% CI 0.02-0.26, P=0.02), but with a longer withdrawn time (pooled WMD 1.05, 95% CI 0.08-1.22, P<0.01). Conclusions Detection rate for flat lesions of the colon and rectum, not for adenoma, can be improved by NBI system and meanwhile its withdrawn time is prolonged, indicating that routine use of NBI system for detecting colorectal adenomas may be recommended only with its further refined technique.

Key words: 
Colorectal neoplasms;  Narrow band imaging;  Meta-analysis
Reply to: “Definition of SPSS: we need to speak the same language”
Authors: Michael Praktiknjo, Jordi Torner, Macarena Simón-Talero, Wenyi Gu, Antoni Perez-Poch, Cristina de la Torre, Inés del Val, Francisco Alpiste, Joan Genescà, Jonel Trebicka
Journal: Journal of Hepatology (2020)
一本值得阅读的好书--《打开临床科研之门》
Authors: 何权瀛
Journal: BMJ (2005)

冯正中医生曾给我寄来他编写的一本有关医学科研方面的专著-- (湖南科学技术岀版社,2003).因为当时正值非典肆虐京城,无暇阅读此书,此事便拖延下来.直到去年国庆节前我去欧洲开会,利用其间空闲时间通读完了这本书,整个阅读过程使我深受启示和促进,最后决定写几点读后体会,也算是对冯正中医生的一番谢意。
Personalized antibodies for gastroesophageal adenocarcinoma (PANGEA): Secondary and final primary efficacy analyses.
Authors: Daniel V.T. Catenacci, Bryan Peterson, Leah Chase, Samantha Lomnicki, Anthony Serritella, Natalie Reizine, Chih-Yi Liao, Lindsay Alpert, Namrata Setia, John Hart, Uzma Siddiqui, Sunil Narula, Murtuza M. Rampurwala, Yuan Ji, Theodore Karrison, Blase N. Polite, Hedy L. Kindler
Journal: Journal of Clinical Oncology (2020)

4561 Background: Targeted therapies (tx) have had limited benefit in advanced (aGEA) due to baseline spatial (primary vs metastatic tumor PT/MT) &amp; temporal molecular heterogeneity (BMH/TMH). We previously reported PANGEA methods &amp; results: 35% BMH rate &amp; 1 0 OS results achieving 1yr OS of 66% &amp; mOS of 16.4 months (m) using the personalized tx strategy (Catenacci et al. GI ASCO 2020 Abstr356). Here we will report the TMH rates at progressive disease points (PD1 &amp; PD2), ORR/PFS/DCR in each of 3 tx lines, time to strategy failure (TTF), &amp; updated OS/safety. Methods: PANGEA enrolled newly diagnosed aGEA pts who then received up to 3 cytotoxic (cx) tx lines (L). Baseline tissue biomarker profiling (BP) was mandated on PT/MT &amp; PD1/PD2, &amp; ctDNA analysis throughout. After initiating 1L cx &amp; upon learning MT BP results, antibody (AN) was added by a predefined prioritized tx algorithm incorporating tissue &amp; blood BP (Table). At PD1, pts went to 2L cx + initial AN. Upon results of PD1 BP, pts changed AN only if BP evolved per tx algorithm. The same was done at PD2. The 1 0 endpoint was 1yr OS; enrolling 68 pts provided 80% power to detect a 63% 1yr OS compared to historical 50% 1yr OS (HR 0.67), using a 1-sided test (0.10 alpha). Results: 80 pts were enrolled, &amp; 68 tx’d per protocol. At data cut-off 2/1/20, 15 pts were still on trial with only 2 of these pts on tx &lt;12m (8 pts in 1L, 5 in 2L, 2 in 3L). All 68 pts had at least 1 dose of 1L tx, 87% 2L tx, &amp; 36% 3L tx. AN assigned by the tx algorithm at 1L, OS, TTF, &amp; ORR 1 /PFS 1 /DCR 1 of 1L tx are shown in Table; 2L &amp; 3L ORR/DCR outcomes will be shown. The 3yr &amp; 4yr OS rates were 12% &amp; 8%. TMH leading to molecular subgroup change by tx algorithm was 51% after 1L &amp; 36% after 2L; details &amp; results by subgroup will be provided. Any grade &gt;3 non-heme tox thru all 3 tx lines was seen in 25% of pts. Conclusions: PANGEA showed superior 1 0 &amp; 2 0 endpoint efficacy, even when excluding HER2- pts, compared to historical outcomes. Clinical trial information: NCT02213289 . [Table: see text]
Biomarker analyses from the phase III CheckMate 214 trial of nivolumab plus ipilimumab (N+I) or sunitinib (S) in advanced renal cell carcinoma (aRCC).
Authors: Robert J. Motzer, Toni K. Choueiri, David F. McDermott, Thomas Powles, Jin Yao, Ron Ammar, Simon Papillon-Cavanagh, Shruti S. Saggi, Brent M. McHenry, Petra Ross-Macdonald, Megan Wind-Rotolo
Journal: Journal of Clinical Oncology (2020)

5009 Background: In CheckMate 214 (NCT02231749), N+I demonstrated superior clinical outcomes vs S in patients (pts) with aRCC. Here, we report exploratory biomarker analyses of pretreatment tumor samples relative to outcomes. Methods: Formalin-fixed, paraffin-embedded aRCC samples were characterized by immunohistochemistry (tumor programmed death ligand 1 [PD-L1], n = 992; PD-L1 combined positive score [CPS], n = 980), whole exome sequencing (WES; tumor mutational burden, indel burden, HLA class I zygosity, and PBRM1 mutation status; n = 481), and RNAseq (n = 213). Gene signature scores were calculated as the median value of Z-scored expression for transcripts. Association with outcome was tested using Fisher’s exact test and Cox proportional hazards model. With ≥ 42 mo follow-up, prolonged progression-free survival (PFS) with N+I ( &lt; or ≥ 18 mo; n = 82 vs 27, respectively) was analyzed by limma and gene set enrichment analysis of Hallmark gene sets (MSigDB). Results: PD-L1 CPS did not have improved predictive power over tumor PD-L1. The WES-derived biomarkers were not associated with outcomes in pts treated with N+I or S. For the RNAseq cohort, objective response rates (ORR) for pts with ≥ median scores, and hazard ratios (HR) relative to &lt; median are shown (Table). A higher angiogenesis (Angio) gene signature score was associated with higher ORR and PFS for S; lower Angio score was associated with higher ORR in N+I. Immune signature scores were not predictive for ORR in N+I. Prolonged PFS with N+I (≥ 18 mo, n = 27) was associated with higher expression of Hallmark inflammatory response and Hallmark epithelial mesenchymal transition (EMT) gene sets (both adjusted P = 0.002). Conclusions: The Angio gene signature was associated with ORR for S (high score) and N+I (low score). Prolonged PFS in 27 pts receiving N+I was linked with inflammation (consistent with findings from PD-1 blockade monotherapy), but associated with EMT-related transcripts (in contrast with findings in other tumor types). Further validation of these exploratory analyses will be required. Clinical trial information: NCT02231749 . [Table: see text]
治疗咳嗽中成药的合理应用
Authors: 吴群励
Journal: BMJ (2010)

咳嗽是临床常见症状,止咳中成药种类名目繁多,许多患者在自行选用,结果是有些见效,有些无效甚至加重,其原因为药证不符.中医治疗咳嗽应遵循中医辨证施治的原则,只有合理治疗才有收效.中医通常将咳嗽分为外感咳嗽和内伤咳嗽,下面具体分析介绍。
Surface-modified nanoparticle transport evaluated in a multistage model of ovarian cancer.
Authors: Stephen Winter, Hunter Miller, Hermann Frieboes, Jill Steinbach-Rankins
Journal: Journal of Clinical Oncology (2020)

e18057 Background: A novel multi-stage model composed of ovarian cancer (SKOV-3) and fibroblast (MRC-5) cells was developed to provide a physiologically relevant in vitro platform to assess nanoparticle (NP) transport and aid in the development of more targeted clinical therapies. This multicellular ovarian tumor spheroid model is customized to the stages of ovarian cancer progression. The model leverages knowledge of these distinct stages in vivo to simulate their respective microenvironment, and thus provide a more accurate platform for evaluation of nanoparticle transport and drug delivery into ovarian tumor tissue. We hypothesized that alterations to the tumor microenvironment (TME) along with inclusion of a peptide-based scaffold (Puramatrix, PMX) to represent the site of metastasis, would lead to enhanced cell growth, migration and altered NP transport, which may be more indicative of the challenging transport conditions encountered in clinical ovarian cancer. Methods: In order to validate the in vitro model, tumor spheroid growth and invasion were evaluated while exposed to stromal cell activation and tissue hypoxia. MRC-5 activation was achieved via the TGF-ß1 mediated pathway, while tissue hypoxia was induced via incubation at 5% oxygen. PEG and MPG surface-modified NP transport was assessed in both stages of the model via confocal microscopy. Results: Consistent with in vivo observations in the ascites and site of distal metastasis, spheroids exposed to an activated stromal microenvironment were denser, more contractile and more invasive than their unactivated counterparts (p &lt; 0.05). Additionally, hypoxic conditions, like those observed in the low pH environment of the ascites, resulted in negative spheroid radial growth over 5 days, compared to an increase for those cultured in normoxic conditions (p &lt; 0.005). MPG-modified NPs exhibited superior tissue penetration relative to PEG-modified NPs in the ascites stage of the model (p &lt; 0.05). Alternatively, PEG NPs enhanced penetration relative to MPG NPs when evaluated under metastatic conditions. In this case, NP transport was attenuated regardless of surface modification, due to the PMX-induced ECM reorganization. Conclusions: A novel multi-stage model, representative of ovarian cancer, was developed to evaluate NP transport in tumor tissue. We evaluated critical conditions in the microenvironment of ascites and metastasis and how these conditions may affect nanotherapy. Future studies will evaluate NP treatments by encapsulating a chemotherapeutic and measuring IC-50 values.
TCGA Kidney Cell Atlas: A differential gene expression database for the dissection of tumor-specific gene modules.
Authors: Saif Alimohamed, James I. Geller, Bruce Aronow
Journal: Journal of Clinical Oncology (2020)

e17078 Background: The Cancer Genome Atlas project has become a leading source for data that has allowed the identification of a broad range of human cancer tumor types and subtypes and has revealed deep complexity with respect to the differentiation, or lack thereof, among human cancers. In particular, differential gene expression analyses have revealed a wealth of active oncogenic pathways, underlying gene mutation drivers, discriminative markers, and candidate therapeutic targets. Despite its rich composition, several factors have led to it not attaining the utility it would seem to offer. Methods: To study this, we dissected molecular subtypes in the TCGA and used the Pan-Kidney (n = 1022 samples) Portion within it to determine where obstacles seem to limit its utility. We re-clustered the renal carcinomas to create more appropriate histology annotations for these samples. The molecular subtypes were then found through K-means using differentially expressed known developmental regulators per histological annotation. After deriving these new annotations, the histology and molecular subtypes were compared to one another via T-test to generate gene modules that characterize these classes/subclasses. Results: We identified a number of factors that include inconsistent metadata attributes, apparent misclassification of histological subtypes, and molecular subtypes that do not match with that obtained by focused approaches to rederive principle subclasses. Our gene modules showed a molecular subtype of clear cell renal carcinoma that was enriched for vascular development and nephron development. In general, the clear cell renal carcinoma and papillary renal cell carcinoma cohorts both showed significant co-expression with atlases that were enriched for genes involved in kidney development. Conclusions: Our atlas highlights the limitations of the current TCGA atlas and provides another tool to capture the rich insights from the TCGA repository through the efforts explained above, highlighted by its use in kidney carcinoma.
Patients prefer "medical labels" to lay language, study finds
Authors: R. Dobson
Journal: BMJ (2003)

GPs need to watch their language when they are diagnosing what's wrong with a patient. Although health professionals are being encouraged to use lay language to improve communication in consultations, patients may actually prefer medical terminology, a new study says.

Patients see a medical label such as gastroenteritis as an assurance that their problem has been taken more seriously, while the equivalent lay label, stomach …
Job satisfaction of general practitioners in Beijing Chaoyang District and influencing factors
Authors: Jie Li, Xin Du, Ting Zhang, Wenhua Wang, Xiaohui Yang, Hui Wang, Hong Du, Changsheng Ma
Journal: BMJ (2018)

Objective
To investigate the job satisfaction of general practitioners in Beijing Chaoyang District and related influencing factors.


Methods
Total 500 general practitioners from 35 community health service centers in Chaoyang District were invited to join this web-based survey in June 2015, and valid response was obtained from 419 of them. Information on the satisfaction to their career, income and practicing environment were collected. Factors associated with job satisfaction were analyzed using Chi-square test and logistics regression respectively, before and after adjustment of common confounders.


Results
Among 419 responders, there were 296 females (70.6%) and 123 males (29.4%) with a median age of 38 years old and median working duration of 15 year; 297 (70.9%) of them had college degree or above; 185 (44.2%) of them saw>120 patients per week and 227 (54.2%) of them worked >40 hour per week; 179 (42.7%) of the responders worked at the outpatient clinics; 180 (43.0%) of them were planning for further education in the next 5 years; 311 (74.2%) of the responders were satisfied with their career, while only 124 (29.6%) of them were satisfied with their income, and 206 (49.2%) were satisfied with the practice environment. The multivariate logistic regression showed that age>40 year (OR=2.20, 95%CI: 1.33-3.61), working  40 year old (OR=2.03, 95%CI: 1.28-3.21), working <40 hours per week (OR=1.60, 95%CI: 1.04-2.46), and planning for further education in the next 5 years (OR=2.03, 95%CI: 1.28-3.22) were positively associated with satisfaction with the income; education lower than university (OR=2.14, 95%CI: 1.37-3.36), seeing<90 patients per week (OR=1.78, 95%CI: 1.18-2.69), working <40 hours per week (OR=1.73, 95%CI: 1.15-2.59), not working at outpatient clinic (OR=1.54, 95%CI: 1.02-2.31) and planning for further education in the next 5 years (OR=1.75, 95%CI: 1.16-2.63) were significantly associated with higher satisfaction with practice environment. Most of the responders thought that there was a shortage of primary care physicians.


Conclusion
General practitioners are generally satisfied with their careers, but are not satisfied with their income and practice environment in Beijing Chaoyang District.


Key words: 
Job satisfaction; Questionnaires; General practitioners
加强对耐药性结核病的认识
Authors: 葛瑛
Journal: BMJ (2005)

当前,全球结核病耐药形势日趋严重,受人类免疫缺陷病毒(HIV)感染以及不合理化疗等因素的影响,耐药结核尤其是耐多药结核(multiple-drug resistance tuberculosis, MDR-TB)病例数急剧上升,估计目前全球耐药结核菌感染者已达5 000万人[1].耐药种类、数量增加使治疗费用增加、临床治愈率下降、病死率上升,结核有可能再次成为难治之症、不治之症。
Safety and efficacy of tazemetostat, an enhancer of zeste-homolog 2 inhibitor, in patients with relapsed or refractory malignant mesothelioma.
Authors: Marjorie Glass Zauderer, Peter Wojciech Szlosarek, Sylvestre Le Moulec, Sanjay Popat, Paul Taylor, David Planchard, Arnaud Scherpereel, Thierry Marie Jahan, Marianna Koczywas, Martin Forster, Robert B. Cameron, Tobias Peikert, Evren Kocabas Argon, Neil Michaud, Jay Yang, Vikram Kansra, Dean A. Fennell
Journal: Journal of Clinical Oncology (2020)

9058 Background: Breast cancer gene 1 (BRCA1)-associated protein 1 (BAP1), a nuclear deubiquitinase, is commonly inactivated in malignant mesothelioma. Preclinical data showed that BAP1 inactivation sensitizes mesothelial cells to inhibition of enhancer of zeste-homolog 2 (EZH2), a methyltransferase implicated as an oncogenic driver in this tumor. This study evaluated the safety and efficacy of tazemetostat (TAZ), a potent and selective EZH2 inhibitor, in relapsed/refractory (R/R) malignant mesothelioma with BAP1-inactivation. Methods: EZH-203 (NCT02860286) was a 2-part, open-label, phase 2 study that assessed the pharmacokinetics (PK), safety, and efficacy of TAZ in pts with R/R malignant mesothelioma. In part 1, pts received TAZ 800 mg QD on day 1 (D1) and 800 mg BID, beginning day 2 of cycle 1 (C1). In part 2, pts received 800 mg of TAZ BID on D1 of C1. A two-stage Green-Dahlberg design was used for part 2. Primary endpoints were PK profiling of TAZ in all pts (part 1), and disease control rate (DCR) at week 12 in pts with BAP1-deficient R/R malignant mesothelioma (part 2). Secondary endpoints included safety, overall response rate (ORR), progression-free survival, overall survival, and duration of response (DOR). Results: The study enrolled 74 pts with R/R malignant mesothelioma, 70 pts (95%) were centrally confirmed to be BAP1-deficient. Median prior lines of therapy were 2 (range, 1-9). Observed clinical data in the presence of CYP3A4 inhibitors and inducers suggest a low DDI potential of TAZ. The 12 week DCR was 47% (n = 35). The ORR per RECIST version 1.1 was 3% [complete response: 0%; partial response (PR): 3% (n = 2)]. Of the 2 patients with PR, 1 had a DOR of 21 weeks and the other is ongoing (15.3 weeks at data cut off). 47 pts (64%) and 21 pts (28%) had stable disease (SD) and progressive disease, respectively. Overall, 91% pts discontinued, either due to disease progression (n = 65), death (n = 5), or treatment discontinuation (n = 1). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in ≤5% of patients, most commonly anemia (5%) and dyspnea (4%). No pts discontinued due to TEAEs. There were no treatment related deaths. Conclusions: Based on disease control rate and stable disease, TAZ showed antitumor activity in pts with BAP1-deficient R/R malignant mesothelioma. TAZ monotherapy was generally well-tolerated. The current data support further clinical evaluation of TAZ in these pts. Furthermore, this trial presents an optimal paradigm for drug development in molecularly-enriched cohorts in mesothelioma. Clinical trial information: NCT02860286.
Trends in primary surgical resection and chemotherapy for metastatic colorectal cancer, 2000-2016.
Authors: Nina Niu Sanford, Michael Ryan Folkert, Todd Anthony Aguilera, Muhammad Shaalan Beg, Syed Mohammad Ali Kazmi, Aravind Sanjeevaiah, Linda Farkas
Journal: Journal of Clinical Oncology (2020)

e16000 Background: When, whether and in whom resection of the primary tumor for patients with metastatic colorectal cancer (CRC) is indicated remains incompletely elucidated, although a recent randomized trial (JCOG1007, presented at GI ASCO 2020) showed no survival benefit in resection of asymptomatic primary tumors in this population. Given the emergence of multiagent chemotherapy, surgery may be used less, but patterns of care for metastatic CRC have not been reported. As such, we sought to evaluate trends in use of primary surgical resection and chemotherapy among patients with metastatic CRC. Methods: Patients diagnosed with metastatic CRC between 2000-2016 were identified from the Surveillance, Epidemiology and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing primary surgical resection, with year of diagnosis as the primary independent variable. The cohort analysis was also stratified by primary site (colon versus rectum), age ( &lt; 50 vs. &gt;50 years) and whether patients also underwent resection of metastatic sites (yes versus no). The secondary endpoint of interest was receipt of any chemotherapy, also assessed by multivariable logistic regression. Results: Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent resection of their primary tumor. The odds of undergoing primary surgery decreased with later year of diagnosis, with patients diagnosed in 2016 61.1% less likely to undergo surgery than those diagnosed in 2000 (AOR 0.39, 95% CI 0.36-0.42, p &lt; 0.0001; absolute percent 62.3% to 43.8%). Black patients and women were also less likely to have surgery (p &lt; 0.001). Similar trends by year for primary surgery were observed among each of the subgroups, although patients with colon primary, young adults (age &lt; 50), and patients also undergoing metastatectomy were more likely to undergo primary surgery (p &lt; 0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with later year of diagnosis, with patients diagnosed in 2016 221% more likely to receive chemotherapy than those diagnosed in 2000 (AOR 2.21, 95% CI 2.04 to 2.40, p &lt; 0.0001; 45.5% to 64.0%). Conclusions: From 2000-2016, we observed a sharp decline in the rate of primary surgical resection for patients with metastatic CRC, while use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC, perhaps with stratification by molecular and clinical characteristics, in order to optimize both cancer-specific and symptomatic outcomes.
"精神病"患者的真相
Authors: 金世红
Journal: BMJ (2009)

我是一名全科医生,所以亲人朋友也自然把我当成了他们的家庭医生,有什么身体上的问题都会先来问问我的意见.家里有位亲戚,男孩,今年18岁,上高三,住在北方的一个小城.听家人讲这孩子从小听话,以前学习成绩也很好,可是,近一年来他的妈妈每次挂电话来都抱怨他变得非常叛逆,厌学,脾气暴躁,常与家人争吵.他外婆用好吃懒做来形容他的状况,因为他不但不学习、不爱做事,还很好吃,有时甚至偷拿父母的钱去买零食.家人对他的行为感到非常失望,都认为他不可救药了,也怀疑他有精神病.电话里听到他的事,我的直觉反应考虑是青春期叛逆的问题,并未考虑到很具体的医学问题。