tbuckley/cabot-search huggingface dataset:
Association of lymph node count and survival after primary retroperitoneal lymph node dissection (RPLND) for testicular nonseminomatous germ cell tumor (NSGCT).
Authors: Hiren V. Patel, Arnav Srivastava, Sinae Kim, Eric A. Singer, Isaac Yi Kim, Thomas L Jang
Journal: Journal of Clinical Oncology (2020)

e17052 Background: RPLND for clinical stage (CS) I &amp; IIA/B NSGCT has both staging and therapeutic implications. Single center studies have reported on the impact of lymph node count on outcome after 1° RPLND for men with NSGCT. However, this has yet to be corroborated in a nationally representative dataset. Methods: Using the National Cancer Database, patients who received a 1° RPLND from 2004-2014 for CS I &amp; IIA/B NSGCT were identified. The analytic cohort was stratified according to LN count (≤20, 21-40, and &gt; 40 LNs). Sociodemographic characteristics were compared among groups. The Kaplan-Meier method was calculated and pairwise comparisons performed. Based on sensitivity analyses to determine LN cutoff that impacts survival, subsequent analysis compared patients with ≤20 and &gt; 20 LNs resected. Multivariate analysis using stepwise regression was used to determine factors associated with receipt of an RPLND with &gt; 20 LNs resected. Results: Of 1,376 men who received 1° RPLND for Stage I or IIA/B NSGCT, 35.6%, 27.4%, and 14% had ≤20, 21-40, and &gt; 40 LNs resected, respectively. LN count was associated with overall survival (OS), with 95%, 97%, and 98% 8-year OS for men with LN count ≤20, 21-40, and &gt; 40 LNs, respectively. OS in men with ≤20 vs 21-40 (p = 0.018) and &gt; 40 LNs (p = 0.042) resected differed significantly. However, no significant difference was observed when 21-40 vs &gt; 40 LNs were resected (p = 0.677). Therefore, subsequent analysis compared those who had ≤20 and &gt; 20 LN resected, and OS between these two groups differed significantly (Figure). Multivariate analysis demonstrated that patients with private insurance, surgery having been performed at an academic center or in the Northeast, and those with pT2 disease were more likely to have &gt; 20 LNs resected at the time of RPLND. Conclusions: Lymph node count after 1° RPLND for NSGCT is significantly associated with overall survival, with more favorable survival seen in those who receive an RPLND with &gt; 20 LNs resected when compared to ≤20 LNs.
The future of TTOM
Authors: Søren Overgaard
Journal: Behavioral and Brain Sciences (2020)

Abstract “Thinking through other minds,” or TTOM, is defined in two different ways. On the one hand, it refers to something people do – for example, inferences they make about others’ expectations. On the other hand, it refers to a particular theoretical model of those things that people do. If the concept of TTOM is to have any future, this ambiguity must be redressed.
咳嗽变异性哮喘的临床特征和诊断标准
Authors: 刘国梁, 林江涛
Journal: BMJ (2009)

咳嗽变异性哮喘(cough variant asthma,CVA)为慢性咳嗽常见的病因之一,以慢性咳嗽为主要表现,其病理生理过程与典型哮喘并无本质区别,一部分CVA者可以发展成为典型哮喘。
Prevention of cisplatin nephrotoxicity (CN) in head and neck cancer patients receiving concurrent chemoradiation (CCRT) by adding oral rehydration solution (ORS) to short hydration regimen: A randomized open-label controlled trial.
Authors: Aungsumal Maisrikrod, Siwat Sakdejayont, Jakkapan Rongmuang, Chirawadee Sathitruangsak, Patrapim Sunpaweravong, Arunee Dechaphunkul
Journal: Journal of Clinical Oncology (2020)

e18560 Background: CN remains a frequent occurrence despite receiving standard fluid hydration, particularly for head and neck cancer patients undergoing CCRT. We aimed to investigate whether adding ORS to short hydration regimen can reduce CN. Methods: We conducted a randomized open-label controlled trial in patients with head and neck cancer receiving CCRT with 3-weekly cisplatin (≥ 60 mg/m²). Eligible patients were randomly assigned to receive short hydration regimen (2000 mL of normal saline on day 1) alone or in combination with 2000 mL of ORS on days -1, 2 and 3 of each cycle. All patients were instructed to drink at least 2000 mL of fluid. The primary end point was the incidence of ≥ gr 1 creatinine (Cr) elevation on day 8. The planned sample size was 160 (80 patients each arm). Results: Thirty-five patients in ORS group and 34 patients in control group (43% of planned sample size) were enrolled. Baseline characteristics were balanced between the two groups, except more patients in ORS group underwent surgery (35.3% vs. 22.9%), and had less feeding tube prophylaxis (76.5% vs. 88.6%), although there were not statistically significant. The mean dose of cisplatin on day 1 was significantly higher in ORS group (91.2 mg/m 2 vs. 85.1 mg/m 2 , p=0.01). There was no difference of volume of total fluid intake and toxicities between the two groups. Less percentage of patients in ORS group developed ≥ gr 1 Cr elevation as shown in the Table, although there were not statistically significant. Conclusions: Although our interim analysis showed no significant difference of CN between the groups, there was a trend that addition of ORS might prevent acute and chronic kidney injury secondary to cisplatin. The completed enrollment is warranted to confirm this early findings. Clinical trial information: TCTR20200207005 . [Table: see text]
An exploratory study of sorafenib plus toripalimab for unresectable hepatocellular carcinoma with portal vein tumor thrombus.
Authors: Yu Yang, Qiu Li
Journal: Journal of Clinical Oncology (2020)

TPS4658 Background: Portal vein tumor thrombosis (PVTT) is common among advanced hepatocellular carcinoma ( HCC), resulting in poor prognosis. As the standard first-line treatment, the efficacy of Sorafenib is not satisfactory in HCC with PVTT. Although immune checkpoint inhibitors have made a breakthrough in treatment of advanced HCC, objective response rate (ORR) of anti-PD-1 monoclonal antibody monotherapy is only 17-20%. Recently, PD-1/PD-L1 inhibitors combined with anti-angiogenesis therapy have shown good efficacy in the clinical studies. However, the data on immunotherapy for HCC with PVTT are still limited. Toripalimab is the first Chinese-produced anti-PD-1 monoclonal antibody marketed. We designed the study to evaluate the efficacy and safety of Sorafenib plus Toripalimab as the first-line treatment for unresectable HCC with PVTT. Methods: The study is a multicenter, single-arm, phase Ib/II trial. The primary objectives are 6-month progression-free survival (PFS) rate and safety. Secondary objectives include ORR, disease control rate, PFS, overall survival. The escalation stage includes two dose cohorts: Sorafenib 400 mg po qd or 400 mg bid combined with Toripalimab 240 mg iv d1 q3w. 6-12 patients are estimated to evaluate the dose-limiting toxicity within the first 42 days of administration. In the expansion stage, patients are treated with the recommended dose based on the escalation stage, until progressive disease or intolerable toxicity. Assuming Sorafenib plus Toripalimab can improve the 6-month PFS rate to 40% (Sorafenib:20%, β = 0.2, α = 0.05) and dropout is 10%, this stage need 39 patients. A total of 45-51 patients are enrolled. Major eligibility requirements include: unresectable HCC with diagnoses confirmed histologically or cytologically, or confirmed clinically in accordance with Chinese guideline for HCC diagnosis and treatment (v2017); radiographic evidence of PVTT; age ≥18 and &lt; 75 years; at least one measurable lesion according to RECIST 1.1; a predicted life expectancy ≥ 3 months; ECOG PS≤1, Child-Pugh class A or B (≤7); no any prior systemic anti-cancer treatment; adequate organ function. Patients with hepatitis B treated with antiviral therapy (viral load &lt; 100 IU/mL) or patients with chronic hepatitis C can be included. The study is open and actively enrolling at time of submission. Clinical trial information: NCT04069949 .
Anakinra for severe forms of COVID-19: a cohort study
Authors: Thomas Huet, Hélène Beaussier, Olivier Voisin, Stéphane Jouveshomme, Gaëlle Dauriat, Isabelle Lazareth, Emmanuelle Sacco, Jean-Marc Naccache, Yvonnick Bézie, Sophie Laplanche, Alice Le Berre, Jérôme Le Pavec, Sergio Salmeron, Joseph Emmerich, Jean-Jacques Mourad, Gilles Chatellier, Gilles Hayem
Journal: The Lancet Rheumatology (2020)
Racial and socioeconomic disparities in overall survival in colorectal cancer (CRC) at West Cancer Center &amp; Research Institute (WCCRI), Memphis, TN.
Authors: Vanessa Wookey, Gabriella Bufalino, Gregory A. Vidal, Bradley G. Somer, Lee S. Schwartzberg, Axel Grothey
Journal: Journal of Clinical Oncology (2020)

e16122 Background: WCCRI, a comprehensive regional community oncology center in Memphis, Tennessee and the Mid-South region, serves a racially, geographically and socioeconomically diverse patient cohort. We sought to evaluate disparity of outcomes in survival by race and socioeconomic status, in addition to patient and tumor characteristics. Methods: All consecutive patients referred to and treated at WCCRI with colorectal adenocarcinoma from 2007-2013 were included. Individual chart review was performed to verify diagnosis, stage, and date and cause of death. Kaplan-Meier Overall Survival curves were generated for the entire cohort and by race, sex, tumor location and income derived from zip code. WCCRI survival data were compared to SEER data. Results: From 2007-2013, 1,176 patients were included in the analysis: 405 blacks, 757 whites, 14 others. Median age at diagnosis: Blacks 58 yrs, whites 61 yrs. Stage distribution at diagnosis: stage 1: 100, stage 2: 275, stage 3: 425, stage 4: 376. All stages combined, blacks trended towards shorter OS vs whites (5-year OS: 52.8% vs 58.3%; median survival 71.0 mos vs 98.6 mos; p= 0.095). Blacks presented at later stages (71.4% at stage 3 or 4 vs 66.3% for whites) but no statistically significant OS differences were seen when compared by stage. Patients at or below the median income of $39,590 for WCC had worse 5-year OS (51.6% vs. 61.1%; p= 0.006), as did patients without private insurance (5-year OS: uninsured: 48.0%, Medicare/Medicaid: 50.0%, private: 62.0%; p&lt; 0.001). Adjusted for stage, 5-year OS was statistically significant for stage 4 (private: 18.0%, Medicare/Medicaid: 9.4%, uninsured: 8.3%; p= 0.020). A higher proportion of blacks were below the median income (69% vs 39%) but no statistically significant OS differences were seen when adjusted by race. Overall, cancer survival outcomes were similar to SEER results. Conclusions: At WCCRI, black patients with CRC presented at a later stage than whites, however, adjusted for stage, no significant racial difference in OS was found. Income and insurance status influenced survival outcomes. Overall, our results reveal racial and socioeconomic disparities in colorectal cancer in a diverse US population and further detailed multivariate data analyses are underway.
Evaluation of blood-based proteomic biomarkers associated with response to anti-PD-1 treatment in NSCLC.
Authors: Nicholas Dupuis, Silvia Lopez-Lastra, Clement Dumont, Vito Dozio, Kristina Beeler, Kamil Sklodowski, Emanuela Romano
Journal: Journal of Clinical Oncology (2020)

e21531 Background: Immune checkpoint inhibitors have remarkably improved the natural history of patients with non-small cell lung cancer (NSCLC), with improved clinical responses and overall survival compared to standard therapy. However, most unselected NSCLC patients do not respond, highlighting the need of theranostic biomarker discovery. In a cohort of NCSLC patients treated with anti-PD-1-blockade, we investigate baseline blood-based parameters with a high-throughput quantitative proteomics workflow, based on data independent acquisition mass spectrometry (DIA-MS). Quantified proteins are evaluated as potential circulating biomarkers for predicting the response to therapy. Methods: Plasma samples from 49 NSCLC subjects treated with anti-PD-1-blockade were prepared for mass spectrometry. All samples were analyzed on a Thermo Scientific Q Exactive HF-X operated in a DIA mode using capillary flow liquid chromatography with separation over a 40 min gradient. DIA data was extracted with Spectronaut to quantify expressed proteins. Results: Across all samples, 605 proteins were quantified and 17 were significantly associated (log2 fold change &gt; 0.58 and q-value &lt; 0.05) with Responders (SD + PR) vs Non-Responder (PD) groups. Functional mapping and unsupervised clustering of regulated proteins identifies three major subject groups based on protein expression profiles: Group A is characterized by high expression of acute phase proteins (e.g. SAA1/2, CRP), Group B has low overall protein expression, and Group C has high expression glycolysis related enzymes (ALDOA, GAPDH) and focal adhesion proteins (VCL). Consistent with previous studies the Group A, with high levels of acute phase proteins, had poor overall survival relative to the other two families (HR = 2.2 [1.2-4.2], p = 0.003). Notably, Group C is comprised largely of Non-Responders (8/12) yet had improved overall survival relative to Group A (HR = 2.5 [1.2-5.0], p = 0.004). Conclusions: Plasma proteomic profiling with capillary flow DIA-MS enables quantification protein profiles in a hypothesis free manner. Poor outcomes on anti-PD-1 therapy was confirmed for subjects with elevated acute phase proteins. However, a subgroup with high focal adhesion and glycolysis proteins had improved survival despite containing non-responder subjects, requiring further investigation.
全科医学学科建设与医院核心竞争力的提升
Authors: 王爽, 刘凤芝, 于晓松
Journal: BMJ (2009)

目前,对综合性教学医院是否需要设置全科医学科,面向社会提供全科医疗服务,尚未达成共识.作者从提升医院核心竞争力的角度,阐述大医院发展全科医疗服务的意义. 一、问题的提出 随着我国医药卫生体制改革的不断深化,以社区卫生服务为基础的新型城市卫生服务体系正在形成并日趋健全,但该项事业的发展遇到合格全科医师短缺、服务能力不强的瓶颈,尽管国务院、卫生部、教育部等部门多次提出高等医学院校及其附属医院应加强全科医学学科建设[1],但在实际执行中举步维艰.据卫生部统计,全国仅有16个省的34家医院被批准为全科医学专科医师培训试点基地,总招生规模897人[2],显然与不断增加的全科医师需求不相适应.而且,多数医院并没有成立单独的全科医学科,将培训任务挂靠在急诊科、老干部科或保健科等科室.出现这些问题的主要原因与全科医疗在综合性教学医院的功能定位存在模糊认识有关。
A novel proteomic mass spectrometry-based approach to reveal functionally heterogeneous tumor clones in breast cancer metastases and identify clone-specific drug targets.
Authors: Nawale Hajjaji, Mira Abbouchi, Lan Anh Nguyen, Samuel Charles, Sarah Leclercq, Delphine Bertin, Yves-Marie Robin, Isabelle Fournier, Michel Salzet
Journal: Journal of Clinical Oncology (2020)

e13063 Background: Breast cancer mortality is expected to rise by almost 30% by 2030 worldwide, mainly due to the occurrence of distant metastases. The development of drugs specifically targeted at tumor drivers has not yet curbed resistance to treatment, which prevents metastases curability. There is a need for new molecular approaches to tackle metastases complex biology, particularly tumor heterogeneity, a main determinant of resistance. The aim of this study was to use a proteomic mass spectrometry-based approach to reveal functionally heterogeneous’ tumor subpopulations in breast cancer metastases, and identify clone specific drug targets. Methods: Metastasis biopsies (n = 21) were collected retrospectively from patients with advanced breast cancer treated at Oscar Lambret Cancer Center (Lille, France). Tumor heterogeneity was analyzed directly on FFPE tissue sections using MALDI mass spectrometry imaging (MSI) on a RapifleX Tissuetyper. Unsupervised spatial segmentation was performed to reveal tumor subpopulations with distinct proteomic profiles within each metastasis. The full proteomic characterization of these tumor clones was further performed with spatially resolved proteomic mass spectrometry. Results: MSI revealed that breast cancer metastases contained 2 to 5 functionally distinct tumor clones (proteomic clones). Although the clone profiles within a metastasis were correlated, unsupervised hierarchical clustering showed a clear distinction between them and specific proteomic signatures. Enrichment analysis showed that differentially expressed proteins were involved in a variety of biological processes or pathways including regulation of histone acetylation, extracellular matrix degradation, DNA repair, NOTCH pathway, estrogen-responsive target genes or exocytosis. The evolution of the proteomic clones profile during disease progression was also determined by comparison of paired biopsies. To identify the candidate treatments best fitted to metastasis heterogeneity, the specific proteomic signatures of the clones were matched against a druggable genome database. It was possible to unveil candidate drug targets personalized to each metastasis functional clone. Conclusions: MALDI mass spectrometry imaging combined with spatially resolved proteomics has the potential to tackle breast cancer metastases heterogeneity, and identify candidate drug targets specific to functional clones to personalize treatments.
Analysis on herbal medicines utilized for treatment of COVID-19
Authors: Lu Luo, Jingwen Jiang, Cheng Wang, Martin Fitzgerald, Weifeng Hu, Yumei Zhou, Hui Zhang, Shilin Chen
Journal: Acta Pharmaceutica Sinica B (2020)

As coronavirus disease 2019 (COVID-19) pandemic poses a substantial global public health threat, traditional Chinese medicine (TCM) was used in 91.50% of the COVID-19 cases in China, showing encouraging results in improving symptom management and reducing the deterioration, mortality, and recurrence rates. A total of 166 modified herbal formulae consisting of 179 single herbal medicines were collected for treating COVID-19 in China. Glycyrrhizae Radix et Rhizome, Scutellariae Radix, and Armeniacae Semen Amarum are the most frequently utilized in clinics, most of which are antipyretic (47, 26.26%), expectorant and cough-suppressing (22, 12.29%), and dampness-resolving (21, 11.73%) from traditional descriptions. A total of 1212 chemical components containing β-sitosterol, stigmasterol, and quercetin were primarily selected. Additionally, using complex system entropy and unsupervised hierarchical clustering, 8 core herbal combinations and 10 new formulae emerged as potentially useful candidates for COVID-19. Finally, following scaffold analysis, self-organizing mapping (SOM) and cluster analysis, 12 clusters of molecules yielded 8 pharmacophore families of structures that were further screened as pharmacological targets in human metabolic pathways for inhibiting coronavirus. This article aims to make more easily accessible and share historical herbal knowledge used in contemporary treatments in a modern manner to assist researchers contain the global spread of COVID-19.
Post-registration experience of nivolumab (nivo) therapy in patients with advanced hepatocellular carcinoma (HCC): An international study.
Authors: Petros Fessas, Ahmed Omar Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Uqba Khan, Bo Yu, Sonal D Paul, Neil satish Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I. Mohamed, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Urban Marron, David James Pinato
Journal: Journal of Clinical Oncology (2020)

e16677 Background: Nivo is FDA-approved in sorafenib-experienced, advanced HCC. Post-registration data to portray treatment in a real-world setting is lacking. Methods: We describe safety and efficacy of nivo in patients (pts) from 8 centres (USA n = 181, Asia n = 47, Europe n = 5), documenting overall (OS), progression-free survival (PFS), overall response (ORR) and disease control rates (DCR) (RECIST). Results: We analysed 233 pts, mostly cirrhotic (n = 176, 75%) due to hepatitis C (n = 95, 54.0%) with Barcelona Clinic Stage (BCLC) C HCC (n = 178, 76.4%), Child-Pugh class (CP) A (n = 158, 67.8%) or B (n = 75, 32.2%), and AFP &gt; 400 IU/mL (n = 132, 56.7%). Nivo was given as first (1L, n = 85, 36.5%), second line (2L, n = 130, 55.8%) or &gt; 2L (n = 18, 7.7%), after local (n = 191, 82%) and systemic therapy (n = 148, 63.5%), mostly sorafenib (n = 142, 60.9%). Median duration of nivo was 6.0 months (mo, interquartile range [IQR] 2.6-11.9) and stopped due to progression (n = 109, 46.8%) or toxicity (n = 8, 3.4%). After median follow up of 7 mo (IQR 3.0-12.3), ORR was 22.4% and DCR was 52.1%. Best responses (n = 219, 94%) included complete and partial responses in 18 (7.7%) and 31 (13.3%) pts respectively, stable disease in 65 (27.9%) and progressive disease in 105 (45.1%), not dissimilar by CP (p = 0.26). Median OS was 12.2 mo (95%CI 8.4-16.0) and predicted by CP (CPA 16.3 mo 95%CI 11.7-20.8; CPB 7.3 mo 95%CI 4.2-10.4; hazard ratio [HR] 1.9, p = 0.01), nivo line (1L 16.3 mo 95%CI 8.0-24.5; &gt; 1L 10.4 mo 95%CI 7.4-13.5; HR 0.68, p = 0.05), and PVT (PVT- 13.8 mo 95%CI 11.7-16.0; PVT+ 10.4 mo 95%CI 7.8-13.0; HR 1.8, p = 0.015) but not cirrhosis, AFP, BCLC or steroid use (p &gt; 0.05). Median PFS was 10.1 mo (95%CI 6.1-14.2), predicted by BCLC (A-B 19.0 mo 95%CI 7.1-30.8; C 8.2 mo 95%CI 4.9-11.4; HR 2.8, p = 0.002) and line (1L 18.2 mo 95%CI 10.4-25.9; &gt; 1L 8.2 mo 95% CI 6.2-10.2; HR 0.60, p = 0.021), but not cirrhosis, AFP, or steroid use (p &gt; 0.05). 26 pts (11.2%) suffered &gt; = Grade 2 toxicities, most commonly fatigue (n = 29, 24.7%). Conclusions: Real-world use of nivo in advanced HCC across line of therapy suggests reproducible clinical efficacy and safety compared to prospective trials.
Evaluation of prognosis of rectal cancer patients with neoadjuvant chemoradiotherapy by clinical TNM stage: Is it suitable?
Authors: Yue Chen, Rui Zhang, Xinxin Dong, Fang Liu
Journal: Journal of Clinical Oncology (2020)

e16029 Background: In the Union for International Cancer Control /American Joint Committee on Cancer TNM classification system, the prognosis of rectal cancer patients with adjuvant treatment are based on pre-radiotherapy clinical TNM stage. However, the value of this classification system is still debated. Here, we find that neoadjuvant pathologic TNM stage may be better than clinical TNM stage in patients with rectal cancer. Furthermore, we propose a novel risk stratification which may be more accurate in the assessment of prognosis of these patients. Methods: Between 2010 and 2015, 316 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy followed by radical surgery were included for analysis. The clinicopathological factors for developing recurrences that affected prognosis were analyzed. Results: Our findings showed that the pathological complete response group had significantly better overall survival and recurrence-free survival than did the non-pCR group. Clinical N stage was not only an independent factor for developing recurrences but was also a significant prognostic factor in the pCR group, just as neoadjuvant pathologic TNM stage in the non-pCR group. Based on the independent prognostic factors, pCR patients were stratified into two recurrence risk categories: pCR with cN0 stage or pCR with cN+ stage. Non-pCR patients were stratified into three recurrence risk categories: non-pCR with ypTNM I stage, ypTNM II stage or ypTNM III stage, which might offer greater potential for the prognosis of patients with rectal cancer. Conclusions: Neoadjuvant pathologic TNM stage, rather than pre-radiotherapy clinical TNM stage, was an independent factor for developing recurrences in the non-pCR group. Furthermore, a novel risk stratification, which may be more accurate in the assessment of prognosis of rectal cancer patients, was proposed.
非手术治疗股骨头坏死
Authors: 张念非, 李子荣
Journal: BMJ (2006)

股骨头坏死是骨科常见的难治性疾病,由多种原因引起,可能通过共同途径导致骨坏死和股骨头结构的破坏.已知的危险因素近百种,现普遍认为非创伤性骨坏死共同的病理生理机制可能是血管内凝血和微循环血栓形成,造成缺血而导致骨坏死,这也是目前非手术治疗股骨头坏死的主要理论依据[1-3]。
Progress of standardized patients in general practice education and training
Authors: Dexin Jia
Journal: BMJ (2018)

The standardized patient or simulate patient (SP) plays treble roles in the clinical teaching and training: the role of a patient, the role of a teacher and the role of an evaluator. The SP has been widely used in clinical skill teaching and assessment in medical colleges and universities at home and abroad. This article reviews the progress of SP in general practice education and training, to provide the knowledge base for promoting its wide application in field of general practice.


Key words: 
Standardized patients; General practice; Teaching training; Examine