tbuckley/cabot-search huggingface dataset:
<i>FSCN1</i> as prognostic marker in borderline tumors of the ovary.
Authors: Ahmed El-Balat, Uwe Holtrich, Thomas Karn, Sven Becker
Journal: Journal of Clinical Oncology (2020)

e18061 Background: Risk factors for invasive recurrence of borderline tumours (BOT) of the ovary are needed. The actin-bundling protein Fascin-1 (FSCN1) is involved in alteration of adhesion and cell motility and has been associated with invasion and metastasis in different cancers. Methods: We studied a retrospective cohort of 124 bordeline tumors of the ovary (BOT) with validated diagnosis by an independent pathologist for expression of FSCN1 as potential prognostic biomarker. Results: We found strong expression of the actin-bundling protein FSCN1 in 62 of these tumors. FSCN1 positive patients were slightly younger (46.9±2.2 vs. 53.3±2.3 years, P = 0.049). Expression of FSCN1 was more frequently detected in BOT with serous compared to mucinous histotype (58/78 [74.4%] vs. 3/41 [7.3%], p &lt; 0.001), and in cases with micropapillary pattern (25/28 [89.3%] vs. 38/98 [38.8%], P &lt; 0.001). In addition, a non significant trend was observed for more frequent expression of FSCN1 among cases with implants (8/10 [80.0%] vs. 55/116 [47.4%], P = 0.095). When we compared progression free survival of the patients we found numerical lower but not statistically significant PFS rates of 90.5±6.4% vs. 94.4±5.4% for 10 years, and 81.4±10.3% vs. 94.4±5.4% for 15 years, in BOT with FSCN1 expression compared to those tumors negative for FSCN1, respectively. Conclusions: Our analysis suggests an association of FSCN1 expression in BOT with micropapillary pattern and implants, which have been linked to inferior prognosis. Cases with FSCN1 expression in our cohort displayed numerical lower PFS rates prompting further studies of this marker.
Perfusion kinetics from clinical DCE mris increase the accuracy of predictions of tumor response to chemotherapy.
Authors: John A Cole, Joseph R Peterson, Tyler M Earnest, Micahel J Hallock, John R Pfeiffer, Tushar Pandey, Eduardo Braun
Journal: Journal of Clinical Oncology (2020)

e12651 Background: Nutrient and drug penetration into any solid tumor are critical determinants of the tumor's response to treatment. They depend on both the density of microvasculature within the tumor microenvironment, as well as the exchange rates of nutrients between the microvasculature and the extracellular space. But these parameters are heterogenous, varying considerably from location to location within the tumor and surrounding tissues. The Toft's model and its analogues date back to the early 1990s, and have been used to estimate vascular density, exchange rates, and extracellular-extravascular volume in a spatially-resolved manner using dynamic contrast enhaced (DCE) MRI's. Unfortunately, accurately extracting kinetic parameters from a DCE time-series requires the images to have a time-resolution of just a few seconds, which is rarely done in clinical practice. Methods: We employ a custom designed parallel algorithm to fit DCE MRI data to an exactly-solved ODE model of tissue perfusion kinetics. Results: Here we describe a simplified model of tissue perfusion that can be fit to DCE time traces with temporal resolutions of 90 seconds or more. We show that for many breast tumors, the vascular density and tissue-vascular exchange rate are such that they give rise to a halo of fast-perfusing tissue on the tumor periphery, and slower-perfusing tissue inside. We then use this model as part of a more comprehensive tumor simulation methodology to predict how different patients will respond to neoadjuvant chemotherapy (NACT). We find that the incorporation of our microvascular model gives rise to significantly more accurate predictions of post-treatment tumor volume. Conclusions: Performing perfusion kinetics analyses on clinical MRIs is both challenging, but critical for accurately predicting how a patient will respond to treatment. Our model, which relaxes the requirement for fine DCE temporal resolution, allows for these analyses to be performed on a larger swath of patients without the need for small volumes of interest, or ultra-fast MRI techniques. Moreover, when used within a broader tumor-modeling framework, our model increases the accuracy of predictions of tumor response to NACT.
Clinical characteristics of systemic lupus erythematosus associated thrombotic thrombocytopenic purpura
Authors: Yang Jiao, Xiaoming Huang, Min Shen, Jialin Chen, Wen Zhang
Journal: BMJ (2014)

We retrospectively reviewed the clinical records of 12 systemic lupus erythematosus (SLE) patients with thrombotic thrombocytopenic purpura (TTP) admitted into Peking Union Medical College Hospital (PUMCH) during October 2008 to September 2013. TTP occurred in 0.45% (12/2 693) of patients with SLE. The median age (2 males, 10 females) was 23 years. Their SLEDAI scores ranged from 12 to 30. All patients had significant thrombocytopenia and renal abnormalities. Ten of them had acute renal failure. Cardiac involvement and neurological deficits were observed in 9 and 8 of them respectively. Eight of them had injuries of more than 4 organs. Renal biopsy of 3 patients revealed lupus nephritis (type Ⅳ, n=2; type Ⅴ, n=1) and thrombotic microangiopathy. Eleven TTP patients received steroid pulse therapy (1 g/d, 3 days) and six of them survived. Six patients were rescued by therapeutic plasma exchange and 4 of them recovered. Among another 6 patients not on plasma exchange therapy, only 3 recovered. Finally 2 died, 3 gave up with exacerbated symptoms after therapy and 7 survived.


Key words: 
Lupus erythematosus, systemic; Purpura, thrombotic thrombocytopenic
全科医生培养之我见
Authors: 龚涛
Journal: BMJ (2011)

随着经济发展，社会进步，公众对健康的要求越来越高，不但希望身体上无病，而且希望有好的生活质量。因此，公众非常在意自己生活的周边地区有所好医院，更希望自己身边有个好医生，以便保障健康、维护健康。但是，目前公众能享受到的医疗条件及健康保障水平并不令人乐观，“看病难，看病贵”的问题一直缠绕着公众和社会。国家已经启动医疗改革，重点是加强基层医疗服务建设，而其中培养合格的全科医生一直是医疗工作、医疗改革中的“瓶颈”。下面就此问题谈一些自己的认识。
Accelerator-based BNCT in rescue treatment of patients with recurrent GBM: A multicenter phase II study.
Authors: Shin-Ichi Miyatake, Shinji Kawabata, Hiromi Goto, Yoshitaka Narita, Minoru Suzuki, Katsumi Hirose, Yoshihiro Takai, Koji Ono, Takanori Ohnishi, Hiroki Tanaka, Takahiro Kato
Journal: Journal of Clinical Oncology (2020)

2536 Background: Boron neutron capture therapy (BNCT) is tumor-selective particle radiation and theoretically efficacious especially for tumors with infiltrative nature, such as glioblastoma (GBM). The aim of this study is to assess safety and efficacy of accelerator-based BNCT (AB-BNCT) using cyclotron-based neutron generator, BNCT30, and 10 B-boronophenylalanine (borofalan( 10 B)) agent, SPM-011, in patients with recurrent malignant gliomas, chiefly GBM. Methods: The multi-institutional open-label, phase II clinical trial for recurrent 27 cases of malignant gliomas (MG) (24 cases were GBM) was conducted with above mentioned AB-BNCT system, using 500mg/kg of SPM-011 (study code, JG002). The patients were enrolled from February 2016 to June 2018. The inclusion criteria are bevacizumab-naïve MG, recurrent after standard treatment composed of XRT and chemotherapy with TMZ. Neutron-irradiation time were determined not to exceed to 8.5 Gy-Eq for scalp dose which was decided by preceding phase I trial. Primary endpoint was 1-year survival rate and secondary ones were median overall survival (mOS), median progression free survival (mPFS) and so on. The results were compared to previous Japanese domestic bevacizumab trial for recurrent GBM (JO22506) which had the similar inclusion criteria with JG002. Results: 1-year survival rate and mOS of recurrent GBM cases in JG002 was 79.2% (95% CI:57.0-90.8) and 18.7 months (95% CI:12.9-23.4) (data cutoff = 20 Jun 2019) respectively, while those of JO22506 was 34.5% (90% CI:20.0-49.0) and 10.5 months (95% CI:8.2-12.4), respectively. Median PFS of JG002 and JO22506 were 0.9 and 3.3 months, respectively. Most important adverse event in JG002 was brain edema. 21 out of 27 cases were treated with bevacizumab after progress disease. Conclusions: AB-BNCT demonstrated acceptable safety and prolonged survival for recurrent MG chiefly GBM. AB-BNCT might produce brain edema somewhat after the treatment, which might be the unavoidable adverse event of re-irradiation for recurrent MG, however that seemed to be controlled with bevacizumab. Clinical trial information: JapicCTI-194742 . [Table: see text]
Cognitions and behavior of cough etiquette of community residents
Authors: Jing Fan
Journal: BMJ (2013)

To explore the cognitions and behavior of cough etiquette of 556 residents in Longhua Community and self-compare the changes of cognitions and behavior before and after health education and training. The results showed that awareness rate of cough etiquette was low before training (senior group: 25.4%, children: 11.9%, young white-collar: 36.1%, immigrants: 14.3%, P 0.05), the other three groups improved after training. And the difference was statistically significant before and after training (P<0.05).


Key words: 
Questionnaires; Health education
Application of regional anesthesia under ultrasonic guidance for establishing puncture path of superficial tumor biopsy
Authors: Qing-hong Jing, Wei-de Dai
Journal: BMJ (2013)

To explore the value of local anesthesia under ultrasonic guidance for establishing puncture path of superficial tumor. A total of 144 patients with superficial tumor received local pre-puncture anesthesia under ultrasonic guidance so that all lesions were targeted. Transient aggregation of narcotics was applied for raised (n=12) or superficial (n=15) skin lesions. The clarity of scanning acoustic window was enhanced, the puncture distance of tumor broadened and the mass of axial changed to obtain a longer lymph node cortex. The damage of blood vessels occurred easily due to tumor closeness to large blood vessel or shortened puncture path in 17 cases. Anesthetic drug was injected between tumor and blood vessels to enlarge the thickness for visualizing the puncture needle tract clearly. And puncture was accomplished under the guidance of color Doppler. Therefore a puncture path can be created effectively with local anesthesia by ultrasonic guidance.


Key words: 
Anesthesia, local; Puncture path
女性尿失禁的非手术治疗
Authors: 罗新
Journal: BMJ (2005)

目前尿失禁的种类及定义尚未完全统一,为大多数学者所接受的分类是,压力性、急迫性、混合性、充溢性尿失禁,它们属于功能性尿失禁;而由尿瘘和畸形所致的尿失禁属于结构异常性尿失禁.通常意义上的尿失禁主要是指功能性尿失禁。
Prevalence of hypertension and blood pressure control rate in patients with type 2 diabetes mellitus in Beijing communities
Authors: Ming-zhao Qin, Shen-yuan Yuan, Han-jing Fu, Gang Wan, Liang-xiang Zhu, Ming-xiao Zhang, Xiang-lei Bu, Jian-dong Zhang, Xue-ping Du, Yu-ling Li, Yu Ji, Xiao-ning Gu, Yue Li, Su-fang Pan, Xue-li Cui, Wei Bai, Yu-jie Chen, Zi-ming Wang, Shu-yan Cheng, Ying Gao
Journal: BMJ (2013)

Objective
To survey the prevalence of hypertension and blood pressure control rate in patients with type 2 diabetes mellitus (T2DM) in Beijing communities.


Methods
Total 2849 patients with T2DM were selected by multi-stage sampling from 15 Beijing urban communities. The patients were surveyed with questionnaire, physical examination and laboratory tests were also performed.


Results
The prevalence of hypertension in T2DM patients was 70.8% (2016/2849), and the patients with blood pressure <140/90 mm Hg (1 mm Hg=0.133 kPa) accounted for 54.8%(1077/1960). The rate of blood pressure control (<130/80 mm Hg) was 17.8% (350/1966); there were significantly difference in triglyceride, fasting glucose, waist circumference and glycosylated hemoglobin levels between patients with blood pressure controlled and those with blood pressure not controlled. Elevation of urinary albumin excretion rate was more common in T2DM patients with hypertension than that in T2DM patients without hypertension.


Conclusions
The prevalence of hypertension is high and the blood pressure control rate is low in T2DM patients of Beijing communities. Multi-risk factor control and effective community-based management for T2DM with hypertension should be emphasized.


Key words: 
Community health services; Diabetes mellitus, type 2; Hypertension; Treatment outcome
合理降脂 --从指南到实践
Authors: 叶平
Journal: BMJ (2005)

血脂异常(dyslipidemia)一般是指血清中的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及甘油三酯(TG)水平高于正常范围及(或)高密度脂蛋白胆固醇(HDL-C)水平低下,也称为高脂血症(hyperlipidemia).流行病学、基础和临床研究均已证实血脂异常与动脉粥样硬化性疾病的关系密切.现就如何依照血脂异常的治疗指南处理药物治疗经常遇到的一些问题作一介绍。
Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC): Genotype and phenotype characteristics in a cohort of 197 patients.
Authors: Ana Beatriz Sanchez-Heras, Adela Castillejo, Juan de Dios García-Diaz, Mercedes Robledo, Alex Teule, Rosario Sánchez, Angel Zuñiga, Enrique Lastra, Mercedes Duran Dominguez, Gemma Llort, Carmen Yague, Teresa Ramon Y Cajal, Consol Lopez, Adria Lopez, Judith Balmana Gelpi, Luis Robles, María Fonfria Esparza, Isabel Chirivella, Luis Gomez, José Luís Soto
Journal: Journal of Clinical Oncology (2020)

1580 Background: HLRCC is a hereditary condition with autosomal dominant inheritance due to germline mutations in the fumarate-hydratase gene ( FH). It is characterized by skin leiomyomas (SLM) in 48-84% of individuals, uterine leiomyomas (ULM) in 30-72%, renal cysts (RCy) and renal cell cancer (RCC) in 15-34%. We aimed to describe the genetics, the clinical features and the potential genotype-phenotype associations in the largest cohort of FH mutation carriers from Spain. Methods: We performed a multicenter, observational, retrospective study of individuals with genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records. We analyzed genetic variants and looked for genotype-phenotype associations. Statistical analyses were performed by IBM-SPSS Statistics-v.22. Results: We included 197 individuals (113 women, 84 men), 74 index cases and 123 relatives. Twenty-seven different variants were detected, 26 pathogenic (12 missense, 5 frameshift, 4 large-deletions, 3 splice-site and 2 nonsense) and 1 variant of unknown significance (missense). Of 182 patients with full skin examination, 64.8% presented SLM (median age 36 years; range 8-85). ULM were diagnosed in 90.3% of 103 women with gynecologic exam (median age 30 years; range 17- 55). Hysterectomy was performed in 62.9% (median age 34 years; range 21-54). Of 153 patients with radiological records, 37.3 % presented RCy. Nineteen patients (10.9%) presented RCC, 11 males and 8 females (median age 37 years; range 10-67). The histological diagnoses were: 14 papillary, of which 10 were type 2; 3 clear cell carcinoma and 2 unclassified carcinoma. Six tumors had stage I, 2 stage II, 3 stage III, 4 stage IV, and 4 not available. The median overall survival among patients at stages 3-4 was 2.9 years [1.3-4.5]. Patients with missense pathogenic variants showed higher risk of developing SLM (p = 0.043) and ULM (p = 0.002) than those with loss of function variants. Conclusions: In our cohort, the frequency of RCC (10.9%) is lower than that published in cohorts of similar sample size. The most frequent histology was the papillary type-2; however, other histological patterns do not exclude HLRCC. Individuals with missense pathogenic variants show higher incidence of SLM and ULM.
Cancer incidence in Behçet's Disease.
Authors: Deniz Can Guven, Ertugrul Cagri Bolek, Sabri Engin Altintop, Burcu Celikten, Burak Yasin Aktas, Sedat Kiraz, Ibrahim Halil Gullu, Omer Karadag, Omer Dizdar
Journal: Journal of Clinical Oncology (2020)

e13583 Background: Previous studies demonstrated increased risk of cancer in systemic autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE) and sjögren syndrome due to uncontrolled inflammation. Behçet’s disease (BD) was also reported to be associated with an increased risk of cancer, although data is limited and differences in study designs was an important issue. In this study, we aimed to assess cancer incidence in a large cohort of BD patients and to compare with the data of the Turkish National Cancer Registry (TNCR) in the same age and gender groups. Methods: The study cohort consisted of BD patients of &gt; 18 years old age and without a prior cancer diagnosis who were prospectively recorded in Hacettepe University Vasculitis Center. Data on any cancer was collected from the patient files. Cancer incidence was compared with age- and gender-specific cancer incidence rates of the normal population retrieved from the 2014 Turkish National Cancer Registry (TNCR) data using standardized incidence rates (SIR). Results: Totally 451 adult cases with BD were included in the study. The median age of the cohort was 43 (20-75) and 52.5% of the patients were males. Eleven cancer cases were observed during a median 124 months follow up. Behçet’s Disease was associated with an increase in cancer risk compared to expected counts in the corresponding age and sex group (SIR 2.84, 95% CI 1.50-4.94, p &lt; 0.001). Cancer risk was particularly increased in men (SIR: 5.63, 95% CI: 2.62–10.70, p &lt; 0.001) compared to TNCR data. Patients with papulopustular lesions had a trend towards a decreased risk of cancer (p = 0.060) and patients using azathioprine had a significantly decreased cancer risk (p = 0.031). Conclusions: This study revealed the cancer risk of patients BD was increased approximately three times compared to corresponding age and sex group. Besides the routine care, increased attention for cancer surveillance is required in the follow-up of BD patients.
高原地区正常儿童红细胞参数参考值调查
Authors: 倪林仙, 樊茂, 周敬静, 徐华, 胥冀
Journal: BMJ (2004)

近年来运用BESSMAN分类法诊断各种类型贫血已广泛应用于临床[1],在红细胞直方图上可以看出红细胞体积分布宽度(RDW)变化,通过自动化血液分析仪各项参数指导临床,但对小儿静脉血红细胞参数报道较少,而且地区间仪器型号不同存在差异.为此,我们对昆明市800例3～14岁儿童进行了静脉血及指血红细胞参数调查,现报道如下。
4-miRNA signature combined with <i>MGMT</i> methylation status in glioblastoma: A multicentric retrospective biomarker analysis with accompanying prospective cohort study.
Authors: Maximilian Niyazi, Daniel F Fleischmann, Guido Reifenberger, Jochen Herms, Joerg Tonn, Claus Belka, Kristian Unger
Journal: Journal of Clinical Oncology (2020)

2517 Background: Previously, we identified a prognostic 4-miRNA signature (built from let-7a-5p, let-7b-5p, miR-125a-5p and miR-615-5p) in glioblastoma patients treated according to the EORTC26981/22981-NCIC CE3 protocol. We present results of a novel external validation and will report on a completed prospective study on blood plasma samples of glioblastoma patients prior to chemoradiotherapy (CRT). Methods: The external validation cohort (n = 103) contained IDH1/2 wildtype tumors with known MGMT promoter methylation from the LMU-Munich (n = 37), the University Hospital Düsseldorf (n = 33) and TCGA (n = 33). Risk groups from the combination of miRNA signature with MGMT promoter methylation were analyzed for overall survival (OS) and prognostic performance using C-index. Within the prospective study (n = 52), blood samples were taken prior to RT, on d42 and d84 (22 cases analyzed up to now). Risk scores were obtained from signature miRNA expression levels in resection or biopsy specimen (retrospective, endpoint OS) and blood plasma (prospective, PFS). Results: The 4-miRNA signature was independent of sex and MGMT promoter methylation (p &gt; 0.1) and defined high-risk (n = 47, med. OS: 16.4months) and low-risk (n = 56, med. OS: 26.9months) patients (HR: 2.08, 95%CI: 1.25-3.46, p = 0.004). Patients with methylated (med. OS: 23.7months, n = 54) compared to non-methylated MGMT promoter (med. OS: 16.8months, n = 49) had superior OS (p = 0.007, HR: 0.48, 95%-CI: 0.28-0.82). Combining the 4-miRNA signature and MGMT promoter methylation resulted in the signature-low-risk/ MGMT-promoter-methylated (med. OS: 37.4months), signature-low-risk/ MGMT-promoter-unmethylated (med. OS: 24.7months), signature-high-risk/ MGMT-promoter-methylated (med. OS: 16.4 months) and signature-high-risk/ MGMT-unmethylated groups (med. OS: 14.3months, Log-rank p = 0.002) with superior prediction performance. Conclusions: We confirmed the 4-miRNA signature as an independent prognosticator in IDH-wildtype glioblastoma while combination with MGMT promoter methylation outperformed other established prognostic factors. Our hypothesis is, that blood plasma samples will allow the risk stratification of glioblastoma patients before CRT. Phenotypic alterations driving its prognostic value remain to be determined and will allow for 1) risk stratified trials, 2) pathway analysis and targeting and 3) testing in healthy subjects to elucidate its screening potential.
NGS-based molecular profiling (a multi-center collaborative, observation study in Japan) highlights pathogenic variants of DNA-repair genes in advanced or recurrent endometrial cancer.
Authors: Hiroyuki Fujiwara, Katsutoshi Oda, Nobutaka Takahashi, Jun Sakata, Akiyo Taneichi, Masae Ikeda, Michihiro Tanikawa, Misako Kusakabe, Akira Mitsuhashi, Yoichi Kobayashi, Hiroshi Yamashita, Nao Suzuki, Azusa Akiyama, Hideki Tokunaga, Naotake Tanaka, Mikio Mikami
Journal: Journal of Clinical Oncology (2020)

e13510 Background: Although tumor molecular profiling has now become prevalent, next-generation sequencing (NGS)-based molecular profiling with adequate annotation is limited in recurrent endometrial cancers. We investigated the frequency of alterations in cancer-related genes in a Japanese cohort of incurable endometrial cancer patients. Methods: We enrolled 102 endometrial cancer patients, who had discontinued standard therapy, and extracted tumor DNA from their formalin-fixed paraffin-embedded specimens. Oncomine Comprehensive Assay v3 (ThermoFisher), which covers 161 cancer genes, was used as a comprehensive NGS assay. We only defined variants with the annotations “pathogenic” or “likely pathogenic.” Oncogenicity and actionability were defined with the Oncomine Knowledgebase and “Chrovis database” ( https://chrov.is/ ). The protocol was approved by the institutional ethics committee at each institute, and written informed consent was obtained from all patients before enrollment. Results: The ratios of pathogenic mutations in the PI3K-AKT pathway were 34.3%, 15.7%, and 3.9% for PIK3CA, PTEN, and AKT1, while those in the receptor tyrosine kinase-RAS-MAPK pathway were 3.9%, 2.0%, 3.9%, and 1.0% for FGFR2, KRAS, NF1, and BRAF, respectively. The pathogenic mutation ratios of TP53, ATM, CTNNB1, and FBXW7 were 21.6%, 3.9%, 10.8%, and 9.8%, respectively. In addition to 5.9% of MSH2 variants (five patients with 5-20% and one patient with 56% variant allele frequency (VAF)), pathogenic variants of BRCA1 and/or BRCA2 were identified in 7.8% (seven patients with 5-20% and one with 40% VAFs). Three fusion genes were identified in three patients ( TPR- NTRK1, ESR1- CCDC170, and TBL1XR1- PIK3CA). “Actionable” gene variants (applicable for clinical trials or approved drug available in Japan) were identified in 49.0% of patients. Candidate drugs for patients with actionable variants included ROS1/TRK, AKT, immune checkpoint, and PARP inhibitors. Conclusions: Molecular profiling in poor-prognostic endometrial cancer highlighted the significance of DNA-repair related genes ( TP53, ATM, BRCA1, and BRCA2) and Wnt-beta catenin signaling pathway, and the infrequent alterations in PTEN and KRAS genes, although PIK3CA was frequently mutated. Our data suggest that targeting DNA repair pathway (including PARP inhibitors), may be a treatment option in certain endometrial cancer patients. Clinical trial information: UMIN000027294.