tbuckley/cabot-search huggingface dataset:
Development and validation of a six-gene signature for predicting prognosis in prostate cancer patients with lymph node metastasis.
Authors: Jinan Guo, Wenzhuan Xie, Mengli Huang, Chan Gao
Journal: Journal of Clinical Oncology (2020)

e17524 Background: Prostate cancer (PCa) patients with lymph node metastasis (LNM) always exhibit poor clinical outcomes. A gene signature that could predict survival in these patients would allow for earlier detection of mortality risk and will also guide individualized therapy. Methods: A prediction model was developed using a public cohort consisting of 623 patients with clinicopathologically confirmed PCa. Data were gathered from cBioPortal and UCSC Xena. Genes expressed differentially in patients with lymph node metastasis versus those without lymph node metastasis were identified. Uni-variate Cox regression analysis and LASSO Cox regression were applied to build a prediction model. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier curves were used to assess the prognostic capacity of the model, followed by external validation using the MSKCC dataset from cBioPortal. Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: We identified a six-gene signature (covering GSDMB, SSTR1, MX1, CCBE1, MYBPC1, and FAM3D) that could effectively identify a high-risk subset of PCa patients. ROC analysis indicated that the signature had a good performance (AUC &gt; 0.7) in survival prediction in both the training and the testing/validation cohorts. Cox regression analysis showed that the six-gene signature could independently predict disease-free survival (DFS) as well, although with lower predictive power. Subgroup analyses showed that signature-based risk score may serve as a promising marker to predict DFS in different subgroups, including stage T2 (HR = 0.12, p &lt; 0.001), stage T3 (HR = 0.29, p &lt; 0.001), TP53-wild-type (HR = 0.22, p &lt; 0.001), TP53-mutated (HR = 0.07, p &lt; 0001), AR pathways-wild-type (HR = 0.2, p &lt; 0.001) and AR pathways-mutated(HR = 0.16, p = 0.0419). The performance of the six-gene signature in LNM+ was stable for stratifying the patients according to risk of deatch (HR = 0.23, p = 0.0333). Moreover, GSEA revealed distinct pathway enrichment features in the different risk groups, where pathways related to DNA repair were more prominently enriched in the high-risk group while the low-risk group had higher enrichment of androgen response. Conclusions: We developed a robust six-gene signature that can effectively classify PCa patients into groups with low- and high-risk group, which may help select high-risk patients who require more aggressive adjuvant target therapy or immune therapy.
彩色超声在膀胱小隆起性病变早期诊断中的应用
Authors: 邢秋, 蔡艳, 许怡韵
Journal: BMJ (2010)

膀胱小隆起性病变是指超声检测显示直径≤2.0 cm以下,膀胱壁呈局部增厚或隆起的组织病变的统称,包括膀胱良、恶性肿瘤,腺性膀胱炎.膀胱的肿瘤占泌尿系肿瘤的首位,发病率逐年上升,若能早期发现,对临床早期诊治具有重要的指导意义。
Necessity of introducing basic rheumatology to general practitioners
Authors: Xiuyan Yang
Journal: BMJ (2017)

风湿免疫病学是一门病种复杂且覆盖面广泛的学科，其复杂性在于它不是以解剖学系统划分，而是以非组织器官特异性的炎症为特征。通过对以系统损害为主的风湿免疫病、以炎症性关节病变为主的风湿免疫病、以骨关节炎为代表的退行性病变和以痛风为代表的代谢性风湿病4个方面的阐述，介绍了这个以非感染非肿瘤性炎症为特征的学科，提高临床医生对风湿免疫病的认识。
Effects of aerobic exercises therapy on platelet function in phase I essential hypertension
Authors: Fang Yuan, Li-xia Wang
Journal: BMJ (2008)

Objective To study the effects of aerobic exercises on platelet function in patients with phase Ⅰ essential hypertension (EH). Methods Low-intensity aerobic exercises therapy was given to 36 patients with phase Ⅰ EH for three months. Changes of their blood pressure, heart rate, platelet aggregation rate (PAGTmax), alpha-granule membrane protein (GMP-140) and mean platelet volume (MPV) werer ecorded and compared to those in 36 normal healthy controls. Results As compared to those in controls,PAGTmax, level of GMP-140 and MPV were all increased in patients with phase Ⅰ EH before exercises therapy(t=15.221, 10. 916 and 16. 401, respectively, all P  0.05). Conclusions Aerobic exercises therapy could be effective in lowering blood pressure in patients of mild EH with increased platelet activation, as well as inhibition ontheir platelet activation.

Key words: 
Aerobic exercise;  Essential hypertension;  Platelet activation
Adjuvant concurrent chemoradiotherapy in extrahepatic cholangiocarcinoma.
Authors: Walid Labib Shaib, Katerina Mary Zakka, Feng Tian, Zhengjia Chen, Pretesh R. Patel, Jolinta Y Lin, Christina Wu, Mehmet Akce, Olatunji B. Alese, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2020)

4583 Background: Resected cholangiocarcinomas are rare and have high relapse rates. Adjuvant chemotherapy is the standard of care (BiLCAP Trial). Adjuvant radiation therapy benefit is not well defined. This study aims to evaluate survival outcomes of the effect of adjuvant chemoradiotherapy compared to chemotherapy in extrahepatic cholangiocarcinoma (EHC) using the National Cancer Database (NCDB). Methods: Patients with resected EHC between 2004 and 2013 were identified from the NCDB using ICD-O-3 histology and topography codes: 8140, 8160, 8161, 8162 and C24.0. Patients with neoadjuvant therapy were excluded from this analysis. Univariate and multivariable analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on treatment received. Results: A total of 236 EHC patients were identified. Males comprised 60.6% and 88.1% were Caucasian. Median age was 64 (range, 31-84) years. The majority were distal (72.0%, N = 157) followed by perihilar (20.6%, N = 45), hilar (6.4%, N = 14) and cystic (0.9%, N = 2). Distribution across stages I-III was 28.8% (N = 68), 56.8% (N = 134), and 14.4% (N = 34), consecutively. Adjuvant chemotherapy was given in 37.7% (N = 89) and adjuvant chemoradiotherapy in 62.3% (N = 147). The median dose of radiation was 50.4 Gy. Adjuvant chemoradiotherapy was mostly given in regional node positive disease (p = 0.016) and negative surgical margin (p = 0.002) compared to regional node negative disease and positive surgical margin, respectively. The use of adjuvant chemoradiotherapy was associated with improved OS compared to chemotherapy alone in univariate (HR 0.64; 95% CI 0.44-0.93; p = 0.019) and multivariable analysis (HR 0.65; 95% CI 0.44-0.96; p = 0.030). Median survival and 1 year-OS for patients that received chemoradiotherapy was 33.8 months (95% CI 28, NA) and 87.7% (80.9%, 92.1%) compared to chemotherapy alone which was 23.8 months (95% CI 18.9, 35.4) and 75.5% (64.9%, 83.3%). Conclusions: Adjuvant chemoradiotherapy was associated with improved survival in patients with resected EHC compared to chemotherapy alone. This conclusion warrants further prospective studies to confirm these results.
脑卒中防治中的新技术和策略
Authors: 张勤奕, 刘伟竹
Journal: BMJ (2010)

张勤奕:在中国有大量脑卒中患者,但却没有一个全面、有效的防治体系.为此,我们于2003年成立了中美脑中风协作组,这个组织云集了血管支架、心房颤动(房颤)、卵圆孔未闭及宣传等方面的专家,旨在通过有效的防治体系,使中国的老人不要因脑卒中而瘫痪,降低其病死率。
肺栓塞心电图的表现及意义
Authors: 何秉贤
Journal: BMJ (2005)

肺栓塞(pulmonary embolism,PE)并不少见,现己成为猝死的主要原因之一,及时正确诊断很重要,但不容易.提高对其的临床认识和心电图(ECG)的诊断水平十分重要,因为ECG是最简捷、廉价、无创的检查方法,虽然对诊断PE不敏感也不特异.临床与ECG结合,对疑诊的患者进一步作心脏B超和多排CT,确诊后及时采用溶栓抗凝等治疗,可使病情转危为安.由于近年来对PE的重视,有关ECG也有不少进展,值得复习。
The Progression of Renal Disease
Authors: Franklin H. Epstein, Saulo Klahr, George Schreiner, Iekuni Ichikawa
Journal: New England Journal of Medicine (1988)

IN the past two decades, clinical and experimental studies have markedly expanded our understanding of the causes of renal disease. Enhanced understanding of the diverse pathogenetic mechanisms (vascular, metabolic, or immunologic disorders) involving the glomeruli, the interstitium, or both has not, however, resulted in commensurate therapeutic advances. Chronic renal insufficiency, once established, tends to progress to end-stage renal failure. Although there are some exceptions, efforts to halt or even slow the progression of chronic renal disease have been unsuccessful.The mechanisms underlying the progression of renal disease have remained obscure for at least two reasons. First, the glomerulus and the . . .
Comprehensive molecular assessment of mismatch repair deficiency in Lynch-associated ovarian cancers using next-generation sequencing (NGS) panel.
Authors: Rachel Soyoun Kim, Leslie E. Oldfield, Alicia Tone, Aaron Pollett, Emily Van de Laar, Stephanie Pedersen, Johanna Wellum, Blaise Clarke, Trevor J Pugh, Sarah Ferguson
Journal: Journal of Clinical Oncology (2020)

1523 Background: Abnormalities in mismatch repair (MMR) gene may be the result of pathogenic germline (Lynch syndrome) and somatic mutations as well as epigenetic events. Abnormalities in MMR have been described in non-serous/non-mucinous ovarian cancer (OC) but few studies have examined the causes of these MMR defects (MMRd). To address this, we have completed targeted mutational and methylation sequencing on MMRd OC cases. Methods: Women with newly diagnosed non-serous/mucinous OC (N = 215) were prospectively recruited from three cancer centers in Ontario, Canada between 2015-18. Tumors were reflexively assessed for MMR protein expression by immunohistochemistry. Tumor DNA was extracted from macrodissected MMRd cases and MMR-intact (MMRi) controls following pathology review. Matched tumor-normal samples were run on a custom NGS panel to identify germline and somatic mutations, copy number variants, rearrangements and promoter methylation in MMR and associated genes. Results: Of the 215 women enrolled in our study, 185 (86%) had OC alone and 30 (14%) had synchronous OC and endometrial cancer. Twenty-eight (13%) cases were MMRd, 11 of which were synchronous. The MMRd cohort had median age of 52.5 years, with mostly stage I (N = 14; 50%), grade 1 or 2 disease (N = 18; 64%) with endometrioid histotype (N = 18; 64%). One patient had recurrence after median follow-up of 33.6 months (13.2-93.6). There was no significant difference in overall/progression-free survival between the MMRd and MMRi patients. Using the NGS panel, Lynch syndrome (LS) was detected in 39% of MMRd cases (11/28; 7 OC and 4 synchronous): 7 MSH6, 2 MLH1, 1 PMS2, and 1 MSH2. Clinical germline sequencing was performed on all cases and verified panel findings. An explanation for the observed MMR phenotype was available for 18/20 deficient cases, including 9/10 MLH1 − /PMS2 − (7 somatic methylation, 1 bi-allelic somatic deletion, 1 germline mutation), 0/1 PMS2 − , 6/7 MSH6 − (6 germline mutations) and 2/2 MSH2 − /MSH6 − (1 germline mutation, 1 bi-allelic somatic mutation). Concordance between clinical and research panel sequencing results was 90%. None of the germline mutations were missed by the panel. Conclusions: Use of our custom NGS panel allows for the streamlined assessment of hereditary and somatic causes of MMR deficiency in OC and may be an attractive screening strategy for LS in this population.
脑电图在癫痫诊断中的应用
Authors: 刘晓燕
Journal: BMJ (2007)

癫痫是神经系统的常见病之一,其本质是脑内电活动的阵发性紊乱引起短暂的神经功能障碍,类似阵发性心律失常引起的心功能障碍.因此脑电图(EEG)在癫痫诊断中的作用与心电图(ECG)在心律失常诊断中的作用同等重要.但由于脑电图不是医学院校教材的重点内容,大多数临床医师对脑电图远不如对心电图了解,从而影响了临床对癫痫的正确诊断和治疗.本文简单介绍脑电图在癫痫诊断中的应用。
Risk factors associated to infectious complications in children with febrile neutropenia induced by chemotherapy: A cohort study.
Authors: Karla Díaz Ramírez, Daniel Ortiz Morales, Marta Zapata Tarres
Journal: Journal of Clinical Oncology (2020)

e22535 Background: Children cancer is the second cause of mortality, most of deaths are related to infectious complications due to immunosuppression provoked by chemotherapy. Febrile neutropenia is one of the most common issues in oncological patients and it’s considered an emergency. Studies have tried risk predicting models implementation, although they still need to be validated, updated and reproducible in different scenarios. The aim of this study was the early identification of conditioning factors to severe infectious complications in patients with febrile neutropenia that would allow taking decisions for diagnosis and treatment. Methods: We present a prospective cohort study that estimated the risk associated to clinical and paraclinical factors and the development of infectious complications in pediatric patients with febrile neutropenia induced by chemotherapy on their admission of an emergency room (ER). The clinical features analyzed were: age, type of cancer, chemotherapy regime, time between chemotherapy administration and ER admission, use of colony-stimulating factors, presence of central venous catheter, highest temperature registered, tachycardia, polypnea, hypoxemia and hypotension. The paraclinical features included were leucocyte, neutrophil and monocyte count, and C-reactive protein levels. Results: From 186 febrile neutropenia events, 101 cases reported infectious complications (54%). Clinical infection was the most frequent issue (38%). On the multivariate analysis we found that the features independently associated to infectious complication were tachycardia (OR1.07, CI95% 1.70-6.99) and highest temperature level reported in the ER (OR1.07, CI95% 1.00-1.13). Conclusions: Febrile neutropenia is the most common complication in pediatric oncological patients and it is related to life-threatening infections and high mortality rate. Risk prediction during the initial assessment in the ER is important to stratify patients and offer target therapy to decrease complications and prolonged hospitalization.
Genomic profile at diagnosis by targeted high throughput sequencing, and real-world clinical outcomes in patients diagnosed with acute myeloid leukemia at a tertiary care cancer center.
Authors: Vivek Sulekha Radhakrishnan, Arunima Bhaduri, Neeraj Arora, Reena Nair, Shreya Bhattacharya, Somanka Sanyal, Vidya Veldore, Mayur Parihar, Saurabh Jayanth Bhave, Jeevan Kumar, VL Ramprasad, Deepak Kumar Mishra, Mammen Chandy
Journal: Journal of Clinical Oncology (2020)

e19515 Background: Acute Myeloid Leukemia (AML) is a highly heterogeneous disease. High throughput sequencing (HTS) has led to the discovery of a number of recurrently mutated genes in AML &amp; has provided a detailed molecular landscape of the disease. This information is now extensively utilised &amp; interpreted in AML. Methods: Retrospective analysis of 47 patients with newly diagnosed AML for those who had both cytogenetic and targeted HTS information at diagnosis, [median age: 44y (12-80y); 24 females] &amp; treated at Tata Medical Center, India between 2013-2019. HTS was performed using Illumina Trusight myeloid panel and/or Thermo Fisher Scientific Oncomine Myeloid panel, and mutation data from the common 28 genes were used. Patients were stratified by European Leukemia Net (ELN) 2010 and 2017 guidelines. Standard of care clinical outcome data was available for all patients. Results: 45 of 47 patients had mutations. The most frequently mutated gene was FLT3 (n = 13, 28.9%), followed by NPM1 (n = 8, 17.8%), and others [ IDH1, IDH2, TET2, CEBPA, and NRAS; n = 7, 15.6%). ELN-2010 classified 6 patients as Favourable (12.8%), 10 as Intermediate-I (21.3%), 25 as Intermediate-II (53.2%) and 6 as Adverse (12.8%) risk groups. One patient migrated to the adverse group from Intermediate-II when ELN-2017 was applied. ELN 2017 re-classification: Favorable (n = 6, 12.8%), intermediate (n = 34, 72.3%), and adverse risk groups (n = 7, 14.9%). Co-occurrence of driver gene mutations was found in NPM1 and FLT3 (8.2%) frequently. Patients with mutations in epigenetic modifiers ( ASXL1, IDH1, IDH2, DNMT3A) had high Variant Allele Frequency (VAF, 40-50%) while those with signaling pathway gene mutations ( NRAS, KRAS) had low VAF (9-25%). At a median follow up of 3.25 years, median overall survival in the three risk groups (favorable, intermediate, adverse) were 11.25 mons, 7 mons and 8 mons respectively, and relapse rates were 16%, 29% and 42% respectively. Conclusions: Early experience from a middle-income real-world setting suggests feasibility of integration of HTS information in practise, as additional prognostic/ predictive information. The pattern of a high VAF in epigenetic modifier gene mutations, potentially as a result of early acquisition during clonal development, needs further evaluation. This data set has helped us initiate a prospective multimodal omics study at our institution.
Oncogenic roles of CEACAM6 in pancreatic ductal adenocarcinoma.
Authors: Daruka Mahadevan, Ritu Pandey, Yuliang Chen, Jacob Essif, Aisha Al-Khinji
Journal: Journal of Clinical Oncology (2020)

e16744 Background: Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a cell adhesion receptor of the Ig-superfamily overexpressed in human Pancreatic Ductal Adenocarcinoma (PDA), enriching to the classical activated stroma subtype. CEACAM6 has multifaceted roles in PDA and is a poor prognostic maker (Pandey et al. Sci Rep 2019). We report functional correlative studies across PDA cell lines with high vs KO vs low of CEACAM6 and a PDX model with a therapeutic Mab. Methods: RNA-Seq and microarray expression data of PDA cell lines were downloaded from GEO using R (4.3), normalized and log transformed for analysis: CEACAM6 high vs. low were assessed for differential gene expression changes. Correlation of CEACAM6 levels with genes of interest was studied and compared with the CEACAM6 KO proteomic profile of HPAF-II cells. CEACAM6 WT vs. KO cells were profiled for protein kinase (PK) activity (PAMChip) and gene expression changes by RNA-Seq. NSG-CD34+ mice bearing PDX were evaluated with a humanized anti-CEACAM6 Mab for anti-tumor activity. Results: Differential expression analyses between PDA cell lines with low vs KO vs high CEACAM6 resulted in identifying similar markers changing in quantitative proteomics. KRT20, SYTL1, SKIL, CES1P1, MAN1A1 were down-regulated and HMOX1, CPNE2, ABCD1 were up-regulated in CEACAM6 low or KO cell lines. Specific PKs are upregulated in CEACAM6 KO enriching to the TK family (EPH A1, 3, 4, 8 and HCK), AGC family (e.g. AKT, PKA) and cellular apoptosis (e.g. BAD). RNA-Seq of CEACAM6 WT vs KO cells reconfirmed the up-regulation of MMP1, IL2RG, ATP6V0D2 and low expression of KRT20, AGK and MAN1A1 in CEACAM6 KO cells. Pharmacologic inhibition with a humanized anti-CEACAM6 scFv-Fc (IgG4) in PDA PDX of NSG CD34+ mice demonstrated ~55% tumor growth inhibition (TGI) with enhanced survival of &gt; 14 days vs. control. Conclusions: CEACAM6 is expressed exclusively in primates and humans and plays multifaceted oncogenic roles in PDA pathogenesis. When CEACAM6 is disrupted, ECM proteins are altered reshaping the stroma, activating specific PKs and priming apoptosis. The therapeutic anti-CEACAM6 Mab possesses anti-tumor activity with associated cellular apoptosis and increased mouse survival.
骨关节炎的社区康复指导
Authors: 李涛, 周谋望
Journal: BMJ (2012)

骨关节炎是中老年人的常见病、多发病.该症除了关节肿胀、疼痛外,还常常引起功能障碍.所以除了药物等临床治疗外,康复治疗不能忽视.本文在简单介绍骨性关节炎临床表现及诊断的基础上,比较详细地介绍了骨性关节炎的康复评定方法,并根据社区的特点介绍了常用的康复治疗方法,对社区的医务人员开展骨性关节炎的康复治疗有较好的指导作用。
Impact of inpatient hospitalization on opiate usage for minimally invasive hysterectomy amongst gynecologic oncology patients.
Authors: Amy Dawn Gee, Shannon Michelle Grabosch, Jeffrey Gavard
Journal: Journal of Clinical Oncology (2020)

e18109 Background: The overdose death rate related to opiates has quadrupled in the last two decades. Up to 27% of chronic opiate users report initiation in the post-op period. Among cancer patients, 10% of opioid-naive patients continue chronic use one year after surgery. Restrictive opiate prescribing has demonstrated promise in other studies. However, lacking from current literature is an analysis of the effect that same day discharge (SDD) has on post-op opiate usage at home. The objective of this study is to evaluate the impact of SDD versus physician-elected observation for 1 to 2 days on acute post-op opiate usage and safety following minimally-invasive hysterectomy (MIH). Methods: This is a prospective observational study of women undergoing MIH. Sixty patients were assigned to either the SDD or hospitalization group at provider discretion based on practice pattern, distance from hospital, or comorbidities. One patient was lost to follow up. Patients were followed through 30 days after surgery. Total opiate usage included the inpatient usage (if hospitalized) and home usage assessed at the post-op visit. Anonymous surveys were used to collect home opiate usage practices, satisfaction, and self-reported risk factors for continued use. Continuous variables were analyzed by independent Student’s t-test and the Mann-Whitney U test. Categorical variables were analyzed using Chi-square test and Fisher's Exact test. Results: 29 SDD and 30 hospitalized patients were available for review. Demographics including age, BMI, tobacco use, and procedure indication were well matched. SDD patients used a median 5.0 (1.5-13.5) versus 8.5 (2.25-14.25) 5mg oxycodone tabs (p 0.33). SDD patients used opiates less for non-pain indications including to sleep (4 vs 9, p 0.24) or relax (3 vs 5, p 0.71). One SDD patient had a complication of a cuff hematoma, which spontaneously drained. There were no readmissions. Only one SDD patient felt she would have benefited from longer stay due to nausea. All hospitalized patients took their own opiates at home while 7 SDD had a family member dispense. Psychiatric disorders were the highest comorbidities in both groups (depression n = 12 and 10, anxiety n = 10 and 12). Conclusions: SDD demonstrated a trend towards less opiate usage, although not statistically significant. Patients did not feel that they needed to stay longer in the hospital. The safety of SDD is supported by lack of readmissions and one minor post-op complication. The high rates of psychiatric disease are a concerning risk factor for chronic use.