tbuckley/cabot-search huggingface dataset:
The effect of transcriptional activity of genes regulating DNA repair and apoptosis on the effectiveness of radiation therapy in rectal cancer patients.
Authors: Natalia G Kosheleva, Marina A. Gusareva, Irina A. Udalenkova, Lyudmila Y. Rozenko, Aliya K. Donskaya, Natalya B. Fatkina, Peter N. Gabrichidze, Anna A. Solntseva, Elena A. Karnaukhova, Julia N. Krokhmal, Ekaterina O. Vasilyeva, Oleg Ivanovich Kit, Denis S. Kutilin
Journal: Journal of Clinical Oncology (2020)

e13531 Background: Preoperative radiation therapy (RT) followed by surgery is the main effective treatment for colorectal cancer. However, some patients do not respond to preoperative RT due to the radioresistance of tumor cells, depending on their molecular characteristics, in particular on the expression of a certain group of genes. The aim of this work was to study the effect of expression of BRCA2, H2AX, RBBP8, CASP9 and BCL2 genes on the effectiveness of preoperative RT for rectal tumors. Methods: In the study, paired biopsy preparations (obtained by VCS before irradiation) of normal and tumor tissues of the rectum (adenocarcinoma G1-2) in 30 patients were used. RT was carried out on a Novalis TX linear accelerator (Varian, USA) (SFD = 2.4 Gy to TFD = 54 Gy). RNA isolation was performed by Chomczynski&amp;Sacchi method. Reverta-L kits were used to synthesize cDNA libraries. Using the RT-qPCR method, the relative expression of 5 genes was determined: BRCA2, H2AX, CASP9, RBBP8 and BCL2 (reference GAPDH, ACTB and B2M). Statistical analysis was performed using the Shapiro–Wilk and Mann–Whitney criteria. Results: 2 clusters of patients were identified that differed in the expression of the BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes. In cluster 1, 81% of patients had increased expression of the CASP9 gene and 100% decreased expression of the BRCA2, H2AX, RBBP8, and BCL2 genes. In cluster 2, the expression of the CASP9 gene was reduced in 100% of patients and the expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was increased in 93%. A subsequent analysis of the results of RT showed that 16 patients had complete tumor regression after RT, while expression of the H2AX and RBBP8 genes was reduced by a factor of 2 (p &lt; 0.05), and the expression of the CASP9 gene was increased by a factor of 4 (p &lt; 0.005) relative to normal tissues. 8 patients showed slight tumor regression, and 6 patients had no regression at all, while their expression of the BRCA2, H2AX, RBBP8 and BCL2 genes was statistically significantly (p &lt; 0.005) 2, 4, 6 and 3 times higher, respectively, and that of CASP9 gene was 4 times lower than in patients with complete tumor regression. Conclusions: The study found that the expression of BRCA2, H2AX, CASP9, RBBP8 and BCL2 genes affects the effectiveness of RT, enhancing it in patients with increased expression of CASP9 and reduced expression of H2AX and RBBP8, and vice versa, the effectiveness of therapy decreases with increased expression of H2AX, RBBP8, BRCA2 and BCL2.
胸腔积液腺苷酸脱氨酶、环磷酸腺苷和环磷酸鸟苷检测的临床意义
Authors: 闻平, 陈蕾, 龚玉华
Journal: BMJ (2007)

以放射免疫法和氨试剂法同时检测48例结核性胸腔积液、27例癌性胸腔积液和31例非结核炎性胸腔积液的腺苷酸脱氨酶(ADA)、环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP).结果显示,结核性胸水ADA活性明显高于恶性胸腔积液和其他炎性胸腔积液,3组cAMP检测结果差异无统计学意义,但恶性胸腔积液中cGMP明显高于非结核炎性胸腔积液,cAMP/cGMP也明显低于炎性胸腔积液,结核性胸腔积液和非结核炎性胸腔积液的cGMP和cAMP/cGMP比值差异无统计学意义;联合检测诊断结核性胸腔积液的敏感性达到95%,特异性为98%;联合检测诊断恶性胸腔积液的敏感性98%,特异性为99%.提示cAMP、cGMP和ADA联合检测可为良恶性胸腔积液的鉴别诊断提供可靠的实验室依据。
补钾不当致高钾周期性麻痹一例
Authors: 曾庆, 张先祥, 魏亮
Journal: BMJ (2004)

患者男,41岁,因四肢瘫痪2 h入院.2 h前睡醒后四肢不能活动,伴心慌、胸闷.入院查体:血压106/76 mm Hg(14.1/10.1 kPa),呼吸22次/min,神清合作,四肢肌张力降低,肌力均为Ⅰ级,心率100次/min ,律齐,无杂音.实验室检查:血钾为1.5 mmol/L.心电图示窦性心动过速,T波倒置,S-T段下移,U波增高达1 mm。
Current status of registered general practitioners in Shanghai Pudong New Area
Authors: Zhiqun Shu, Xiaoming Sun, Zhaohui Du, Shengbing Zhang, Jiquan Lou, Limei Jing
Journal: BMJ (2019)

The data of registered general practitioners (GPs) in Shanghai Pudong New Area from 2014 to 2017 were collected through literature review and institutional investigation. The status of registered GPs was analyzed longitudinally by the methods of descriptive statistics and comparative analysis. The total number of registered GPs in Pudong New Area was increased from 1 227 in 2014 to 1 469 in 2017 and increased by 19.7%, with an average annual growth rate of 6.18%. But the human resources of GPs in Pudong New Area were not sufficient and the recruitment of GPs in grass-roots increased slowly. GPs in community health service centers in remote rural areas steadily increased year by year, however, the uneven distribution still existed. The proportion of GPs with senior professional titles had steadily increased, but it was still low.

Key words: 
General practitioner; Talents construction; Health resource
多系统萎缩伴一过性视幻觉一例
Authors: 李宝栋, 白晶
Journal: BMJ (2006)

患者女,60岁,因进行性走路不稳2年,小便失禁1年,于2005年1月12日入院.2年前无明显诱因出现走路不稳,左右摇晃,沿直线行走困难,同时出现言语欠清及发音节律改变.1年前除上述症状进行性加重外,还出现小便失控和双手持物不稳.2年来曾就诊于乡镇医院,因疗效不佳和自身经济所限未到上级医院诊治.发病以来无明显智能障碍及记忆力减退.既往无高血压、心脏病、糖尿病史,无肝炎、结核病史,否认外伤、手术、中毒、脑炎及药物食物过敏史.无家族史及精神病史.查体:血压卧位时138/90 mm Hg(1 mm Hg=0.133 kPa),立位时119/70 mm Hg.神经系统检查:神志清楚,记忆力、注意力、定向力、判断力、智能、情感等均未见异常.言语含混不清,有时呈暴发性.粗测视力、视野正常,双眼左、右注视时呈现水平性眼震。
Integrative assessment of the effect of renal function on ribociclib treatment and dose recommendation in advanced breast cancer patients.
Authors: Yan Ji, Vitaly Yartsev, Yingbo Wang, Michelle Quinlan, Paolo Serra, Tanay Samant, Karen Rodriguez-Lorenc
Journal: Journal of Clinical Oncology (2020)

e13037 Background: Ribociclib is an orally administered CDK4/6 inhibitor used in combination with endocrine therapy (ET) to treat women with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative advanced breast cancer (ABC). An integrative assessment was conducted to evaluate the effect of renal function on the pharmacokinetics (PK), efficacy and safety of ribociclib. Methods: To assess the effect of mild and moderate renal impairment, a subgroup analysis was performed to evaluate PK parameters of ribociclib following oral administration of 600 mg QD 3 weeks on/1 week off in two Phase 1/2 and one Phase 3 clinical trials. Steady-state PK exposures in ABC patients at the 600 mg dose was estimated by a population PK model developed based on a pooled dataset from five Phase 1 to 3 trials and were compared by renal function. Efficacy and safety were also analyzed by renal function in a Phase 2 and three Phase 3 trials in ABC patients. The effect of severe renal impairment on ribociclib PK was assessed in a Phase I study in non-cancer subjects following a single oral 400 mg dose. Results: PK analyses in cancer patients showed that both single-dose and steady-state exposure of ribociclib at the 600 mg dose in patients with mild or moderate renal impairment were comparable to patients with normal renal function. Estimated steady-state PK exposure in patients with mild or moderate renal impairment is also comparable to patients with normal renal function. The primary efficacy results of progression free survival (PFS) and the safety profiles were comparable across renal-function cohorts in ABC patients. In non-cancer subjects administered a single oral dose of 400 mg, ribociclib AUCinf and Cmax increased 2.67- and 2.30-fold in subjects with severe renal impairment, respectively, compared to subjects with normal renal function. Conclusions: PK, efficacy and safety of ribociclib are consistent across patients with normal renal function, mild or moderate renal impairment. Hence, no dose adjustment is required in mild or moderate renal impaired patients. Severe renal impaired patients are recommended to have a reduced dose based on PK data in non-cancer subjects.
Effect of CCND1 amplification on immunosuppression and the association with a poor prognosis to immune checkpoint inhibitors in solid tumors.
Authors: Yingying Huang, Chuan-ben Chen, Yu Chen, Xuan Gao, Yi Li, Jing Lin, Yan-Fang Guan, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

e15249 Background: CCND1 amplification relevant to malignant biological behavior exist in solid tumors. The prevalence and utility of CCND1 amplification as a biomarker for the clinical response to immune checkpoint inhibitors (ICIs) therapy is unknown. Methods: This study included three cohorts: Geneplus Institute ( n= 6536), The Cancer Genome Atlas ( n= 10562) and Memorial Sloan Kettering Cancer Center ( n= 106109). Comprehensive profiling was performed to determine the prevalence of CCND1 amplification and their correlation with the prognosis and the response to ICIs. Results: CCND1 amplification occurs in many cancer types, correlates with shorter overall survival and inferior outcomes with ICIs therapy. Transcriptomic analysis showed various degrees of immune cells exclusion, including cytotoxic cells, T cells, CD8 + T cells, DC cells, B cells in the tumor microenvironment (TME) in a CCND1 amplification population. The gene set enrichment analysis suggested that CCND1 amplification correlates with multiple aggressive, immunosuppressive hallmarks including epithelial mesenchymal transition, TGF-β signaling, KRAS signaling, PI3K/AKT/mTOR signaling, p53 pathway and hypoxia signaling in solid tumors. Conclusions: Our study indicated that CCND1 amplification may be a key point related to immunosuppression in TME and multiple malignancy hallmarks, and it hinders not only the natural host immune responses but also the efficacy of ICIs in solid tumors.
HER2 heterogeneity in adenocarcinoma of the distal esophagus and stomach.
Authors: Rogier Butter, Gerrit Hooijer, Myrtle van der Wel, Jos Bart, Susan ter Borg, Loes van Velthuysen, Marc J. van de Vijver
Journal: Journal of Clinical Oncology (2020)

4567 Background: Patients with HER2 positive adenocarcinoma of the esophagus or stomach are eligible for HER2 targeted therapy, which can improve survival in selected patients. Previous research shows that HER2 gene amplification and HER2 overexpression is frequently heterogeneous within these tumors. Biopsies taken from heterogeneous tumors for predictive testing may therefore result in false-negative outcomes. The objective of this study was to assess HER2 amplification and expression in biopsies and paired resection specimens with adenocarcinoma of the esophagus or stomach, from patients who did not receive neoadjuvant systemic therapy. Methods: Paired biopsies and resection specimens of patients with adenocarcinomas of the esophagus or stomach were retrospectively selected. Immunostaining was performed on all samples using antibody 4B5 (Ventana Medical Systems) and Silver-In-Situ-Hybridization was performed in selected cases. Scoring for HER2 was performed according to the method described by Hofmann et al. (2008). Results: We included 378 cases for analysis. In both biopsies and resection specimens 14% of the cases were HER2 positive. Intratumor heterogeneity in HER2 positive tumors was present in 45% ( n= 24/53) in biopsies and 75% ( n= 39/52) in resection specimens. In HER2 positive resection specimens, 65% ( n= 34/52) of paired biopsies were also positive. In the 18 remaining discordant tumors (resection HER2 positive, biopsy negative), intratumor heterogeneity was present in 16/18 cases. For HER2 negative resection specimens all paired biopsies were also HER2 negative. SISH was performed in 110 tumors. Agreement of HER2 gene amplification between biopsy and resection specimens was observed in 86% (n = 95/110). Five HER2 negative biopsies were positive in the resection specimen. Conclusions: The results of this study indicate that predictive HER2 assessment in adenocarcinoma of the esophagus or stomach can lead to false negative results based on biopsies. As a result, patients with HER2 positive tumors can unintentionally be denied neoadjuvant HER2 targeted therapy. The set of patients investigated in this present study is unique because of the absence of any systemic and/or radiation therapy between the biopsy and the resection of the tumor. Hopefully these results can help in developing methods for improved patient selection for HER2 targeted therapy.
Advances in research on the relationship between frailty and depression in the elderly
Authors: Tiru Shan, Hua Li
Journal: BMJ (2019)

As a complex geriatric syndrome, frailty is characterized by a decrease in strength, endurance and physiological function, which increases the risk of fall, disability, hospitalization and death in the elderly. Depression is one of the common mental diseases in the elderly. It is also a risk factor of weakness, which promotes the development of weakness and interacts with each other. More and more attention has been paid to the research on weakness and depression. This article reviews the recent research progress concerning frailty and depression in elderly patients.

Key words: 
Aged; Depressive disorder; Frailty
Studying Workflow and Workarounds in Electronic Health Record–Supported Work to Improve Health System Performance
Authors: Kai Zheng, Raj M. Ratwani, Julia Adler-Milstein
Journal: Annals of Internal Medicine (2020)

Clinical workflow is the enactment of a series of steps to perform a clinical activity. The transition from paper to electronic health records (EHRs) over the past decade has been characterized by profound challenges supporting clinical workflow, impeding frontline clinicians' ability to deliver safe, efficient, and effective care. In response, there has been substantial effort to study clinical workflow as well as workarounds-exceptions to routine workflow-in order to identify opportunities for improvement. This article describes predominant methods of studying workflow and workarounds and provides examples of the applications of these methods along with the resulting insights. Challenges to studying workflow and workarounds are described, and recommendations for how to approach such studies are given. Although there is not yet a set of standard approaches, this article helps advance workflow research that ultimately serves to inform how to coevolve the design of EHR systems and organizational decisions about processes, roles, and responsibilities in order to support clinical workflow that more consistently delivers on the potential benefits of a digitized health care system.
A retrospective single-center study investigating the clinical significance of grade in triple-negative breast cancer.
Authors: Caroline M. Hamm
Journal: Journal of Clinical Oncology (2020)

e13108 Background: Triple negative breast cancer is defined as estrogen (ER), progesterone (PR), and human epidermal growth factor receptor (HER-2) proteins negative. The grade is the degree of similarity of tumor cells to normal cells under microscope and is an important biomarker of overall patient outcomes or prognosis with higher grades having a poor prognosis. As recent chemotherapy trials noted moderately undifferentiated grade 2 tumors showing higher rates of relapse, we hypothesize that grade can also be a predictive biomarker or determinant of response to specific treatment. Methods: We reviewed 305 patient charts of triple negative breast cancer patients from 2004-2017 at Windsor Regional Cancer Center analyzing the significance of grade with respect to oncological variables, survival-time, and time to relapse. Statistical analysis was performed using Fleming-Harrington, Pairwise Testing, and COX regression, where applicable. Results: Univariate analysis showed statistically significance difference in chemotherapy type (P = 0.008) and a marginal one in ER &amp; hormone therapy status (P ~0.09) between the grades. The overall survival rates were 90.12%, 64.4%, and 77.2%, for grade 1, 2, 3 respectively. The overall difference in survival among the three groups was statistically significant, based on Fleming-Harrington test (P = 0.019). Comparing only between grade 2 and grade 3, we found that after five years, grade 2 patients had a 5.5-fold increased risk of death (HR = 5.5; 95% CI 1.2-25.6) and 2-folds higher risk of relapse (HR = 1.9; 95% CI 1.1-3.2). Grade 3 does significantly better than grade 2 in time to relapse with relapse rates of 70%, 55.6 %, and 75.6%, respectively for grades 1, 2, and 3 (P = 0.04). Conclusions: Tumor grade has a significant positive predictive value in determining relapse with grade 2 tumors demonstrating poorer disease-free survival as compared to grade 1 &amp; 3, less time to relapse, and increased risk of death. This has implications in stratifying triple negative breast cancer patients by grade in future clinical trials while ongoing research yields new targets for chemotherapy.
The effect of primary granulocyte-colony stimulating factor prophylaxis on incidence of febrile neutropenia in patients with testicular germ cell tumors.
Authors: Nikola Hapakova, Michal Chovanec, Katarina Rejlekova, Katarina Kalavska, Jana Obertova, Patrik Palacka, Valentina De Angelis, Zuzana Sycova, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2020)

e17056 Background: Testicular germ cell tumors (GCTs) represent only one percent of all solid tumors; however, they are the most common solid malignancy in men 15-35 years old. Febrile neutropenia (FN) is a grievous complication of chemotherapy, frequently occurring in GCT patients. The aim of this retrospective study was to assess the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in GCT patients. Methods: This study was conducted using the National Cancer Institute medical records database. Patients diagnosed with germ cell tumors treated with first line/adjuvant chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017 were eligible. Starting in January 2006, patients received G-CSF prophylaxis after every cycle of chemotherapy. Results: Out of 393 patients, 265 patients received primary G-CSF prophylaxis and 128 patients did not receive prophylaxis. The majority of patients (69.97%) were treated with bleomycin, etoposide and cisplatin chemotherapy. There were 61 deaths (15.5%) in our study population. 2- and 5-year OS of the study group was 86.8% and 83.1%, respectively. During the study period, 71 patients (18.1%) suffered FN events. Out of 128 patients who did not receive primary prophylaxis, 42 (32.8%) patients suffered FN, while only 29 (10.9%) patients with primary prophylaxis suffered FN ( P = 0.0000001). On subgroup analysis, FN incidence decreased in all groups with primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy. Patients receiving G-CSF prophylaxis had significantly longer overall survival when compared to patients without prophylaxis. (HR = 0.44, 95% CI 0.26-0.75; P = 0.0009). Conclusions: Primary G-CSF prophylaxis was associated with significantly decreased FN incidence and longer overall survival in patients treated with first line chemotherapy and should be consider in all patients except stage I disease.
Harms of CT scanning prior to surgery for suspected appendicitis
Authors: Rogers William, Hoffman Jerome, Noori Naudereh, 陈雷
Journal: BMJ (2015)

在本短文中，我们比较了术前行CT扫描来确诊阑尾炎，而非基于外科医生的临床判断，行直接手术的风险和获益。我们得出以下结论，普遍行CT检查的益处是避免了12例不必要的阑尾切除术，但是这12例不手术的代价是CT扫描将导致1例患者因肿瘤死亡。
Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: An international, multicenter propensity matched study.
Authors: Collin K Chin, Kenneth JC Lim, Katharine L Lewis, Preetesh Jain, Yun Qing, Lei Feng, Chan Cheah, John Francis Seymour, David Ritchie, Kate Burbury, Constantine Si Lun Tam, Nathan Hale Fowler, Luis Fayad, Jason Westin, Sattva Swarup Neelapu, Fredrick B. Hagemeister, Felipe Samaniego, Christopher Flowers, Loretta J. Nastoupil, Michael Dickinson
Journal: Journal of Clinical Oncology (2020)

8021 Background: Transformation of untreated indolent B-cell lymphoma (Tr-iNHL) is associated with poor outcomes. Current practices are extrapolated from prospective studies of de novo large B-cell lymphoma (DLBCL) or small retrospective studies. High dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) is used as consolidation in first remission (CR1) in some centers but the evidence-base is weak. Methods: CLL/SLL, MCL as primary diseases and non-DLBCL transformations were excluded. Propensity score analysis (PSM) using the “greedy match” algorithm was used to match the baseline covariates to adjust for potential selection bias. Landmark analysis was performed with time zero at 3 months after completion of front line chemotherapy (FLC). Kaplan-Meier method and the Cox proportional hazards model were was used for time-to-event analysis including progression-free survival (PFS) and overall survival (OS). Results: 319 transplant eligible patients (age &lt;75, LVEF &gt;45%, no severe lung disease, CR by PET or CT &gt;3 months after FLC) who received &gt;/= standard RCHOP intensity FLC were identified across three centers in Australia &amp; US. 283 (89%) patients had follicular lymphoma, 30 (9%) marginal zone lymphoma, 6 (2%) other subtypes. 49 patients underwent HDC and ASCT in CR1, a matched cohort of 98 pts based on age, stage, HGBL-DH and ECOG PS at diagnosis was generated with a 1:2 ratio using PSM. After a median follow-up of 3.6 (min: 0.1, max: 18.3) years, ASCT was associated with significantly superior PFS on multivariable analysis (MVA) (HR 0.51, 0.27-0.98; P=0.043). Univariate analysis demonstrated a trend towards inferior OS in the ASCT cohort (HR 2.36; 0.87-6.42; P=0.092) with more deaths in the ASCT arm due to PD (8% v 4%). Of the 40 patients (41%) with relapsed disease in the non-ASCT cohort–15 patients underwent salvage HDC &amp; ASCT with 7/15 (47%) ongoing CR; 10 patients underwent CAR-T therapy (5 relapse post ASCT, 4 refractory disease, 1 relapse post FLC) with 6/10 (60%) ongoing CR; 3 patients underwent allogeneic SCT (2 relapse post ASCT, 1 relapse post FLC) with 2/3 (67%) ongoing CR. Conclusions: Although ASCT in CR1 may improve initial duration of disease control in de novo Tr-iNHL, the impact on OS is less clear with effective salvage therapies in the CAR-T era.
孟鲁司特钠对轻中度哮喘患者临床疗效和肺功能的影响
Authors: 王华强, 谈红
Journal: BMJ (2004)

观察孟鲁司特钠对轻中度哮喘患者临床疗效和肺功能的影响. 1. 对象与方法:门诊63例轻中度哮喘患者均符合 中的诊断标准[1].用随机双盲法将门诊63例轻中度哮喘患者分为2组,加服孟鲁司特钠治疗组32例,年龄(39±11)岁;对照组31例,年龄(36±12)岁.
解读《痔诊治暂行标准》
Authors: 杨新庆
Journal: BMJ (2005)

2000年4月中华医学会外科学分会肛肠外科学组讨论制定的 (以下简称 )对痔在临床诊治起到指导作用,同时也推动了学术上对痔的深入研究.根据国内外医学的最新进展和广大医务工作者在临床应用后提出的意见和建议,中华医学会外科学分会肛肠外科学组2002年9月在福建省召开了 的修订会议.经与会专家、学者的认真讨论,对 [1]做了修订。