tbuckley/cabot-search huggingface dataset:
Onset of cardiovascular disease risk factors in women with and without a history of breast cancer: The Pathways Heart Study.
Authors: Marilyn L. Kwan, Carlos Iribarren, Romain Neugebauer, Jamal S Rana, Mai Nguyen-Huynh, Richard Cheng, Zaixing Shi, Monika Izano, Cecile Laurent, Valerie S. Lee, Janise M. Roh, Margarita Santiago-Torres, Hanjie Shen, Dawn L. Hershman, Lawrence H. Kushi, Heather Greenlee
Journal: Journal of Clinical Oncology (2020)

12017 Background: Women with a history of breast cancer (BC) are at increased long-term risk of dying from cardiovascular disease (CVD). However, the onset of CVD risk factors in women with BC has not been well-described. We compared risk of incident CVD risk factors in women with and without BC enrolled in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed between 2005-2013 were identified and matched 1:5 with controls on birth year, race/ethnicity and KPNC membership at the date of BC diagnosis. Cox regression models assessed the hazard of incident hypertension (based on diagnosis codes and filled prescriptions), dyslipidemia (based on diagnosis codes, filled prescriptions, and lab values), and diabetes (KPNC Diabetes Registry). Models were adjusted for baseline BMI, menopausal status, smoking status, neighborhood median household income, education, prevalent CVD conditions, and other baseline CVD risk factors. Subgroups of women who received chemotherapy, radiation therapy, and endocrine therapy were compared with controls. Results: A total of 14,942 women with a new diagnosis of invasive BC were identified and matched to 74,702 controls. On average, women were 62.0 years, 28.3 kg/m 2 BMI, 64.9% non-Hispanic white. Overall, cases were more likely to develop hypertension (HR: 1.18, 95% CI: 1.13, 1.24) and diabetes (HR: 1.23, 95% CI: 1.16, 1.31). Across the board, receipt of any of the three therapies (chemotherapy, radiation therapy and endocrine therapy) was associated with increased risk of hypertension and diabetes, compared to controls. Risk-factor specific hazard ratios for receipt of chemotherapy were (HR 1.18, 95% CI: 1.10, 1.27) and (HR 1.38, 95% CI: 1.26, 1.51), for hypertension and diabetes, respectively. For receipt of radiation therapy, risk-factor specific hazard ratios were (HR: 1.17, 95% CI: 1.09, 1.26) and (HR: 1.15, 95% CI: 1.04, 1.27), for hypertension and diabetes, respectively. Risk-factor specific hazard ratios for receipt of endocrine therapy were (HR: 1.22, 95% CI: 1.14, 1.30) and (HR: 1.16, 95% CI: 1.06, 1.27), for hypertension and diabetes, respectively. Conclusions: The risk of developing hypertension and diabetes is increased in women with BC who received chemotherapy, radiation therapy, and/or endocrine therapy. Future studies should examine the roles of CVD risk factor diagnosis and management on cardiometabolic risk in women with a BC history.
Interventional treatment for hemorrhage following hepatic biliary and pancreatic surgery
Authors: Jia-sheng Huang, Xuan Wang, Wei Chen
Journal: BMJ (2012)

Interventional management was performed in 10 patients with hemorrhage following hepatic biliary and pancreatic surgery.The super-selection arterial embolization was performed in 9 patients using gelfoam pledgets (n =6 ) or metal coils (n =3 ),the procedure was combined with local infusion of reptilase; 1 case was managed by local infusion of reptilase alone.Selective angiography revealed the pseudoaneurysm in 3 cases,contrast media extravasation in 6 cases; in 1 case no obvious bleeding site was found The interventional treatment was successful and hemorrhage stopped in all patients,including one case with reptilase alone with a successful rate of 10/10.The results indicate that interventional treatment is a safe and effective method for hemorrhage following hepatic biliary and pancreatic surgery.

Key words: 
Hemorrhage;  Embolization
Network-based approaches elucidate differences within APOBEC and clock-like signatures in breast cancer
Authors: Yoo-Ah Kim, Damian Wojtowicz, Rebecca Sarto Basso, Itay Sason, Welles Robinson, Dorit S. Hochbaum, Mark D. M. Leiserson, Roded Sharan, Fabio Vadin, Teresa M. Przytycka
Journal: Genome Medicine (2020)

Abstract Background Studies of cancer mutations have typically focused on identifying cancer driving mutations that confer growth advantage to cancer cells. However, cancer genomes accumulate a large number of passenger somatic mutations resulting from various endogenous and exogenous causes, including normal DNA damage and repair processes or cancer-related aberrations of DNA maintenance machinery as well as mutations triggered by carcinogenic exposures. Different mutagenic processes often produce characteristic mutational patterns called mutational signatures. Identifying mutagenic processes underlying mutational signatures shaping a cancer genome is an important step towards understanding tumorigenesis. Methods To investigate the genetic aberrations associated with mutational signatures, we took a network-based approach considering mutational signatures as cancer phenotypes. Specifically, our analysis aims to answer the following two complementary questions: (i) what are functional pathways whose gene expression activities correlate with the strengths of mutational signatures, and (ii) are there pathways whose genetic alterations might have led to specific mutational signatures? To identify mutated pathways, we adopted a recently developed optimization method based on integer linear programming. Results Analyzing a breast cancer dataset, we identified pathways associated with mutational signatures on both expression and mutation levels. Our analysis captured important differences in the etiology of the APOBEC-related signatures and the two clock-like signatures. In particular, it revealed that clustered and dispersed APOBEC mutations may be caused by different mutagenic processes. In addition, our analysis elucidated differences between two age-related signatures—one of the signatures is correlated with the expression of cell cycle genes while the other has no such correlation but shows patterns consistent with the exposure to environmental/external processes. Conclusions This work investigated, for the first time, a network-level association of mutational signatures and dysregulated pathways. The identified pathways and subnetworks provide novel insights into mutagenic processes that the cancer genomes might have undergone and important clues for developing personalized drug therapies.
Identification and validation of stromal immunotype predict survival and benefit from neoadjuvant chemotherapy in patients of breast cancer.
Authors: Fei Ji, Ci-Qiu Yang, Liulu Zhang, Mei Yang, Jieqing Li, Hong-Fei Gao, Teng Zhu, Min-Yi Cheng, Kun Wang
Journal: Journal of Clinical Oncology (2020)

e15261 Background: Immune infiltration of breast cancer is associated with clinical outcome. A growing number of research suggests the diversity of functionally distinct cell types that make up the immune response. The aim of this study was to determine whether differences in the cellular composition of the immune infiltrate in breast cancer influence survival and treatment response, and construct the stromal immunotype which could improve prediction of neoadjuvant therapy and survival. Methods: A total of 1502 ER negative breast cancers from TCGA and METABRIC cohort were used to infer the proportions of 22 subsets of immune cells, Another 200 ER negative breast cancer patients from Guangdong Provincial People’s Hospital in the validation cohort were also included in the study. Immune cell infiltration was evaluated by immunohistochemical staining or CIBERSORT method, Five immune features were selected out of 22 immune features to construct immunotype based on LASSO Cox regression model. Results: Of the cell subsets investigated, CD8+ T cells (p &lt; 0.001), CD4+ T cells (p = 0.002), B cells (p = 0.003), M1 macrophages(p = 0.006) were associated with favourable outcome. T regulatory cells(p = 0.005) emerged as the most strongly associated with poor outcome. T regulatory cells were associated with pathological complete response to neoadjuvant chemotherapy (p = 0.012). Using the LASSO model, we classified ER negative breast cancer patients into stromal immunotype A subgroup (CD8+T high CD4+T high B cell high M1 macrophage high Treg low ) and stromal immunotype B subgroup (CD8+T low CD4+T low B cell low M1 macrophage low Treg high ). Significant differences were found between immunotype A and immunotype B in the combined cohort with 10-year overall survival (66.2% vs. 49.8%; P &lt; 0.001) and 10-year disease-free survival (63.8% vs. 44.4%; P &lt; 0.001). Stromal immunotype was revealed to be an independent prognostic indicator in multivariate analysis in all cohorts separately, and also showed to be related to pCR in neoadjuvant chemotherapy. Finally, stromal immunotype A showed higher immune checkpoint molecules (PD-L1, PD-1, CTLA-4) expression and three important cytokines expression profiles (IL-2, INF-γ and TGF-β). Conclusions: The stromal immunotypes could predict survival and recurrence of ER negative breast cancer patients effectively. Furthermore, the immunotypes might be a practical predictive tool for immunotherapy.
Risk factors of ipsilateral breast tumor recurrence in triple-negative or HER2-positive breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy.
Authors: Mizuho Tazo, Yasuyuki Kojima, Atsushi Yoshida, Sayuka Nakayama, Ryu Tokui, Tomoko Ogawa, Takashi Kuwayama, Takahiro Nakayama, Hideko Yamauchi, Koichiro Tsugawa, Seigo Nakamura, Naoki Hayashi, Makoto Ishitobi
Journal: Journal of Clinical Oncology (2020)

e12599 Background: To date, patients undergo breast surgery after neoadjvant chemotherapy (NAC) even though they achieve clinical complete response (cCR). The safety of omitting breast surgery for the patients who are predicted to be pCR has recently investigated in some research, however we still have not reached to a definite consensus yet. We may consider the breast surgery omission on the assumption that the rate of ipsilateral breast tumor recurrence (IBTR)after achieving pCR is acceptably low. The purpose of this study is to examine the rate of and evaluate the clinical features of IBTR in patients achieving pCR after NAC. Methods: In this study, a total of 278 patients with HER2-positive or Triple negative type primary breast cancer were enrolled from4 institutions. They were all diagnosed as ypT0 after breast conserving surgery and received postoperative radiotherapy. Occurrence of IBTR and other clinicopathological factors were collected by retrospective chart review. Results: Of the 278 patients, 49 patients (18%) were ER+/HER2+, 106 patients (38%) were ER-/HER2+ and 123 patients (44%) were ER-/HER2-. We found breast recurrence in 11 patients (4%) as a first recurrence. The 5-year breast recurrence rate was 4.5% in total, 2.2% in ER+/HER2+, 4.0% in ER-/HER2+ and 4.6% in ER-/HER2-, respectively. There was no significantly difference among subtypes. Interestingly, the 5-year breast recurrence rate of patients under 40-year-old was 12.3% which was significantly higher than patients with and above 40-year-old (3.1%, p=0.002). Conclusions: We should be extremely careful when consider omitting breast surgery for patients younger than 40 even if they achieved pCR after NAC.
Common mental disorder and evaluation of psychical state related to organ transplantation
Authors: 张晶璟, 季建林
Journal: BMJ (2008)

器官移植已成为治疗器官功能衰竭的有效手段,是20世纪医学进展最令人瞩目的学科之一.随着新型免疫抑制剂的使用以及移植后的长期随访管理制度的建立等,全世界的器官移植数量在过去10年里增长很快.然而,器官来源的短缺在很大程度上限制了器官移植的发展.供体和受体之间数最的不平衡性导致了等待器官时间的延长,增加了等待序列中受体的死亡率.随着以往的生物医学模式向现今的生物-心理-社会医学模式的转变,国内外学者对器官移植患者出现的情绪障碍、心理排斥反应、心理同化现象以及患者的心理社会功能康复、心理社会因素等给予了广泛关注,患者的精神和心理问题正如传统的医学问题一样,也会影响器官移植最终的成功与否[1].本文综述与器官移植相关的精神状况评估及常见的精神障碍概况.
A mid-chemoradiation dynamic risk model integrating tumor features and ctDNA analysis for lung cancer outcome prediction.
Authors: Everett J Moding, Mohammad Shahrokh Esfahani, Barzin Nabet, Yufei Liu, Jacob J. Chabon, Jianzhong He, Yawei Qiao, Ting Xu, Luyang Yao, Saumil Gandhi, Zhongxing X. Liao, Millie Das, Kavitha Ramchandran, Sukhmani Kaur Padda, Joel W. Neal, Heather A. Wakelee, Billy W. Loo, Steven H. Lin, Ash A. Alizadeh, Maximilian Diehn
Journal: Journal of Clinical Oncology (2020)

9046 Background: Circulating tumor DNA (ctDNA) molecular residual disease after curative intent therapy predicts disease progression in localized lung cancer. We hypothesized that integrating pre-CRT features and ctDNA levels during chemoradiation therapy (CRT) can predict patient outcomes earlier to enable response-adapted therapy. Methods: We identified pre-CRT features prognostic of disease progression after CRT for Stage II-III non-small cell lung cancer (NSCLC) in a historical “pre-CRT” training cohort of 109 patients. In addition, we applied CAPP-Seq ctDNA analysis pre-CRT and a median of 21 days into CRT (mid-CRT) to a “ctDNA” training cohort of 42 patients treated at MD Anderson and an independent validation cohort of 21 patients treated at Stanford. Prognostic pre-CRT features and mid-CRT ctDNA concentration were integrated using a Bayesian proportional hazards approach to generate a Continuous Individualized Risk Index (Kurtz et al. Cell 2019) for NSCLC (CIRI-NSCLC) to predict freedom from progression (FFP). Results: Adenocarcinoma histology (HR 2.6, P = 0.0005) and KEAP1 mutation (HR 2.7, P = 0.002) but not stage (P = 0.16), age (P = 0.60), or gender (P = 0.98) were significantly associated with FFP in the pre-CRT training cohort. Mid-CRT ctDNA concentration as a continuous variable was significantly associated with FFP in the ctDNA training cohort (HR 1.6, P = 0.04), and applying an optimal threshold identified in the training cohort (3.2 hGE/ml) significantly stratified FFP in the independent ctDNA validation cohort (HR 4.8, P = 0.02). CIRI-NSCLC enabled individualized real-time updating of the probability of FFP as model features became available over the course of CRT. CIRI-NSCLC outperformed individual model features in the independent validation cohort when compared by C-statistic (CIRI-NSCLC: 0.85; mid-CRT ctDNA: 0.76; histology: 0.66; KEAP1: 0.60). Across the whole cohort, patients with a greater than 66% risk of progression predicted by CIRI-NSCLC (n = 10) had an FFP of 10.0% at 12 months while patients with a less than 33% risk of progression predicted by CIRI-NSCLC (n = 22) had an FFP of 79.7% at 12 months (HR 15.0, P &lt; 0.001). Conclusions: Our results suggest that CIRI-NSCLC can identify patients at very high and low risk of progression. Prospective evaluation will be necessary to test the potential utility of adapting treatment based on CIRI-NSCLC.
非胰岛素类降糖药物的联合应用
Authors: 王国兴
Journal: BMJ (2010)

2型糖尿病(T2DM)的主要病理生理是胰岛素抵抗和胰岛素分泌缺陷,胰岛素水平随糖尿病时期的不同而变化,糖尿病早期有代偿性高胰岛素血症,但是大多数糖尿病患者最终发生胰岛功能衰竭,导致循环胰岛素的绝对不足.T2DM患者单药治疗的达标率随糖尿病病程的延长而降低,2种或2种以上不同机制的降糖药物的联合使用可提高血糖控制的达标率。
Family intervention on patients with essential hypertension
Authors: Xiu-lan Zhang, Hui Hou, Li Liu
Journal: BMJ (2008)

Two hundred and thirty two patients with essential hypertension were divided into intervention and control groups (116 in each) ,by the end of study period (from January 2005 to January 2006) 106 patients in intervention group (91.4%) and 102 in control group (87.9%) completed observation.The main findings were as follows: the blood pressure control rate in intervention group was higher than that in controls (X2=23.92,P <0.01) ;the family adaptability(X2 =31.12,P <0.01),family caring(X2=37.90 ,P<0.01),family communication (X2= 17.91,P<0.01) and family function(X2 = 8.26,P<0.01)in intervention group were better improved than those in control group.The results suggest that family can be effective resources for improvement of patients with essential hypertension.

Key words: 
Hypertension; Family
外科治疗原发性甲状旁腺功能亢进症伴高血钙危象二例
Authors: 张真稳, 朱妍, 程英英, 潘云龙, 王艳, 陈平, 金明国
Journal: BMJ (2007)

例1 女,30岁.因四肢关节疼痛、行走困难伴消瘦4个月,于2003年5月入院.近半年来身高下降8 cm,2个月来有多饮、夜尿增多.入院查体:意识清楚,消瘦体型,右颈部可及3 cm×2 cm的包块,质地中等,无压痛,胸廓畸形,两肺呼吸音清,心率120次/min。
Genomic mapping to identify mutations in RYR2 and AHNAK in basal-like breast tumors expressing PD-L1.
Authors: Francisco J Cimas, Aránzazu Manzano, Mariona Baliu Piqué, Pedro Perez, Ádám Nagy, Atanasio Pandiella, Balazs Gyorffy, Alberto Ocana
Journal: Journal of Clinical Oncology (2020)

1027 Background: Basal-like breast cancer is a specific subtype of breast tumors with limited therapeutic options. Although treatment with the anti-PD-L1 antibody atezolizumab has recently shown clinical activity in this setting, not all patients do respond even expressing high levels of PD-L1. In the present article we explored the presence of mutations in breast cancer tumors with high expression of PD1 and PD-L1 with the aim to identify molecular correlates associated with outcome. Methods: We used RNA-seq and mutational data from 971 breast cancer patients using the TCGA dataset, to identify mutations in patients with high levels of PD1 and PD-L1. Data analysis was performed using DESeq R and MAFTools Bioconductor packages. Transcriptomic signatures from the identified mutations were associated with outcome using the Kapplan-Meyer Plotter tool. We correlated the identified transcripts with immune populations using TIMER online tool and correlation between genes with Cancertool online platform. Results: We identified co-occurrent mutations in RYR2 and AHNAK in 8% and 5% of basal like tumors, respectively, in patients with high levels of PD1 and PD-1. The transcriptomic signature of these mutations conferred good prognosis for relapse free survival (RFS) and overall survival (OS). CXCL9 for RYR2 and GBP5, C1QA, IL2RG, CSF2RB and IDO1 for AHNAK were the most relevant genes identified in these signatures. Expression of CXCL9, GBP5, IL2RG and IDO1 correlated with the presence of immune cell populations mainly dendritic cells. This signature, including CXCL9, GBP5, C1QA, IL2RG, CSF2RB and IDO1 classified patients with favorable RFS (HR 0.27 CI 0.2-0.30; p = 1.1e-16) and OS (HR 0.18 CI 0.09-0.34; p = 6.8e-9). This signature showed a stronger prediction capacity compared with already described immunologic signatures. Finally we identify that LAG3 was the only gene commonly present in both signatures and correlated positively with the expression of PD1 and PD-L1. Conclusions: We describe two novel mutations which transcriptomic signatures associated with favorable outcome in basal-like tumors that express elevated levels of PD1 and PD-L1. Future studies should be performed to confirm the role of these mutations and signatures in relation with clinical activity of PD1/PD-L1 inhibitors.
Student loan debt and visa status influence on career choices for hematology and medical oncology fellows in the United States.
Authors: Karam Al-Issa, Sravanti Rangaraju, Ahmad Abdelfattah Al-Hader
Journal: Journal of Clinical Oncology (2020)

11024 Background: There are multiple factors influencing future career plans for US hematology/oncology fellows. The objective of this study is to evaluate the effects of student loan debt and visa status as potential factors affecting their career choices. Methods: A total of 159 US hematology/oncology fellowship programs were contacted, program directors forwarded the survey to current hematology/oncology fellows and recent graduates (classes of 2019, 2018 and 2017). The survey consisted of 13 questions regarding their student loan debt and visa status, research experience, initial career plan, current career for graduates, the influence of student loan debt and visa status on their career decisions (academic, private practice, industry), and whether or not their training programs had resources or mentorship to help them deal with those factors. We used a scale of 1-5 to determine how much each factor affected career choice (1 = extremely unaffected, 5 = extremely affected). Results: A total of 220 physicians have participated, 177 (80.5%) fellows and 43 (19.5%) graduates. For graduates, 35% had student loans during fellowship, 40% of them thought that their loans affected their career choice with a score of 4-5. 93% of graduates with student loans answered that they weren't aware of resources/mentorship to address their loans effect on their career. 44% of graduates were on J1/H1 visa during training, 74% of them thought that their visa status affected their career choice with score of 4-5. 63% of graduates who were on visa answered that they weren't aware of resources/mentorship to address visa status as a factor influencing their career options. For current fellows, 51% have student loans, one third of them thought that their loans affected their career choice with score 4-5. 77% of fellows with student loans answered that they weren't aware of resources/mentorship to address their loans effect on their career. 16% of current fellows are on J1/H1 visa, 66% of them thought that their visa status is affecting their career choice with score 4-5. 62% of fellows who are on visa answered that they weren't aware of resources/mentorship to address visa status as a factor influencing their career options. Conclusions: Hematology/oncology fellows report that student loan debt and visa status are important factors affecting their career decisions. The majority of hematology/oncology fellows in this survey weren’t aware of resources or mentorship to help deal with these factors. Mentors need to be aware of these factors to help fellows achieve their career goals.
星状神经节联合穴位阻滞治疗头痛100例
Authors: 余桃英, 董卿
Journal: BMJ (2005)

我院自2000年7月至2004年3月采用星状神经节阻滞联合穴位阻滞治疗头痛100例,疗效满意,现报告如下. 1.对象与方法:男42例,女58例;年龄18～70岁,平均(47±3)岁;病程1～12年.其中血管痉挛性头痛23例,神经性头痛27例,眼源性头痛2例,鼻源性头痛 7例,肌挛缩性头痛28例,颈椎病所致头痛3例,原因不明10例.均排除颅内占位性病变。
应用炎症反应器官功能不全评分动态评估危重病患者病情的研究
Authors: 姜胜, 杨丽, 黄子通, 蒋龙元, 王庸晋
Journal: BMJ (2006)

重复应用炎症反应器官功能不全评分(IRODS)对重症监护室(ICU)患者的病情进行量化评分,考察生存组和死亡组患者不同时间点IRODS的差异以及IRODS动态评估患者病情的价值.结果示生存组和死亡组间在入住ICU当时、24 h、48 h、72 h、第5天和第7天的IRODS差异有统计学意义(P＜0.01);入住ICU各时间点相应IRODS的接受者操纵特征曲线下面积(AUROCC)分别是0.930、0.934、0.934、0.940、0.914和0.963,均大于0.9.提示IRODS可用于动态评估危重患者的病情和预后。