tbuckley/cabot-search huggingface dataset:
Personalized neoadjuvant strategy in luminal A breast cancer to increase breast conserving surgery (BCS) rate [PLATO study].
Authors: Ji Gwang Jung, Hong Kyu Kim, Yumi Kim, Han-Byoel Lee, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han
Journal: Journal of Clinical Oncology (2020)

TPS603 Background: The most important and well established benefit of neoadjuvant therapy for breast cancer patients is increased breast conservation rate. However, in ER-positive and HER-2 negative breast cancer, the response to neoadjuvant chemotherapy (NCT) is not as good as other subtype of breast cancer, such as HER-2 or triple-negative breast cancer. In addition, with the advancement of multi-gene assay tools for this subtype, adjuvant chemotherapy is not needed at all in significant proportion of this subtype. Through a selective neoadjuvant therapy, either chemotherapy or endocrine therapy using histopathologic markers and 70-gene assay (Mammaprint. Agendia inc.), we hypothesize that we could increase the breast conservation rate in ER-positive and HER-2 negative breast cancer. Methods: This study is a non-randomized, phase II, prospective study. The main inclusion criteria is women with stage I-IIIA, ER-positive and HER-2 negative breast cancer that tumor size is measurable. BCS is not feasible considering the tumor size, location, and patient's breast size. Two surgeons in each institution will judge the feasibility of BCS. Main exclusion criteria is diffuse malignant microcalcification or multicentric breast cancer. The conversion rate from BCS-ineligible to BCS-eligible with NCT was 35.8% in ER-positive and HER-2 negative breast cancer in our previous study. We assumed that with the study regimen, the rate will be increased to 50.8% (15% increase). Given these estimates, under 10% type II error rate and 90% power, 122 patients in total will be enrolled from nine tertiary hospitals in Korea. All the patients initially will be tested with Mammaprint assay. When the Mammaprint result is high risk, the patients will receive NCT. When the Mammaprint result is low risk, the patients will receive neoadjuvant endocrine therapy. Postmenopausal women receive letrozole 2.5mg per day for 16 weeks. Premenopausal women receive leuprorelin every 4 weeks with letrozole for 16 weeks. Period of neoadjuvant endocrine therapy can be prolonged maximum 24 weeks by physician’s decision. The primary endpoint is conversion rate from BCS-ineligible to BCS-eligible of more than 50%. The secondary endpoint is actual breast conservation rate, pathologic complete response, clinical response rate, and disease-free survival. Clinical trial information: NCT03900637 .
Recurrence risk stratification by Dutch clinical risk criteria for early-stage luminal breast cancer patients in Taiwan: A population-based analysis.
Authors: Lei Lei, Han-Ching Chan, Wang Xiao Jia, Tzu-Pin Lu, Skye Hung-Chun Cheng
Journal: Journal of Clinical Oncology (2020)

e12509 Background: Dutch clinical risk criteria (low-risk definition: age &gt; 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n = 2679) and 5-year OS (n = 2636) between low-risk and high-risk groups (in both endpoints, P &lt; 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusions: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective.
FORK-seq: replication landscape of the Saccharomyces cerevisiae genome by nanopore sequencing
Authors: Magali Hennion, Jean-Michel Arbona, Laurent Lacroix, Corinne Cruaud, Bertrand Theulot, Benoît Le Tallec, Florence Proux, Xia Wu, Elizaveta Novikova, Stefan Engelen, Arnaud Lemainque, Benjamin Audit, Olivier Hyrien
Journal: Genome biology (2020)

Abstract Genome replication mapping methods profile cell populations, masking cell-to-cell heterogeneity. Here, we describe FORK-seq, a nanopore sequencing method to map replication of single DNA molecules at 200-nucleotide resolution. By quantifying BrdU incorporation along pulse-chased replication intermediates from Saccharomyces cerevisiae , we orient 58,651 replication tracks reproducing population-based replication directionality profiles and map 4964 and 4485 individual initiation and termination events, respectively. Although most events cluster at known origins and fork merging zones, 9% and 18% of initiation and termination events, respectively, occur at many locations previously missed. Thus, FORK-seq reveals the full extent of cell-to-cell heterogeneity in DNA replication.
A web app nomogram based on real-life patients: Guide decision in first-line treatment for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Maysa Tamara Silveira Vilbert, Natasha Carvalho Pandolfi, Marcelle Goldner Cesca, Poliana de Andrade, Vinicius Fernando Calsavara, Bruno Cezar de Mendonça Uchôa, Ricardo Lima Coelho, Marcelo Corassa, Jose A. Rinck, Aldo A. Dettino, Thiago Bueno Oliveira
Journal: Journal of Clinical Oncology (2020)

e17538 Background: mCRPC phenotype involves androgen-receptor signalling mechanisms that support the use of abiraterone/enzalutamide (Abi/Ez). These therapies improve overall survival (OS) and quality-of-life, with a favourable safety profile. There is no validated data defining the best drug or sequence to be used. Methods: A retrospective study evaluated if a nomogram helps the decision-making of first-line for mCRPC. The nomogram evaluated time-to-treatment failure (TTF) from Abi/Ez and Docetaxel (Doc) treatment and had C-índex of 0.726. Time from start of androgen deprivation therapy to Abi/Ez or Doc, pain, Gleason score, testosterone and the lowest PSA in castration-sensitive scenario were analysed. All patients (pts) in Doc group used second-line Abi/Ez. The outcomes were: to evaluate whether the nomogram scores were associated with TTF/OS in Abi/Ez population; to compare OS between Abi/Ez and Doc poor prognostic (PP) groups based on the nomogram scores. Kaplan-Meier and Cox-regression models were used for time-to-event analyses. The cut-off was defined by Log-Rank. Statistical significance was fixed at 0.05. Results: From May/12 to Feb/20, 123 pts were assessed (79 received first-line Abi/Ez and 44 Doc). Median follow-up was 25.7 months (1.6 to 93.7). Nomogram scores based on Abi/Ez treatment (medium score of 65, 0-225) were statistically associated with OS (HR 1.02, 95% CI 1.01-1.02, p &lt; 0.001) and TTF (HR 1.02, 95% CI 1.02-1.03, p &lt; 0.001). 79 pts who received Abi/Enz were stratified as having good (GP) (score &lt; 46), intermediate (IP) (score 46-112) and PP (score &gt; 112), and it was associated with 75%, 25-75% and 25% probability to 1-year free from treatment failure, respectively. Pts with GP (n = 24) had a median TTF of 29.8m (15.4-44.2), IP (n = 44) 9.8m (4.1-15.4) and PP (n = 11), 4m (2.5-5.5), p = &lt; 0.001. Pts with GP achieved higher TTF than IP (HR 2.3 95% CI 1.3-4.2 p = 0.005) and PP (HR 8.9 95% CI 3.8-20.6 p &lt; 0.001). The results were similar for OS, once the median for GP was 54.0m (30.5-77.6); IP 34.8m (32.2-37.5); and PP 13.6m (9.3-17.9), p = 0.023 (GP versus IP: HR 2.1 95% CI 1.01-4.4 p = 0.046; GP vs PP: HR 3.6 95%CI 1.4-9.6 p = 0.011). Pts with a higher score and PP from Abi/Ez group were compared with Doc pts at first-line (n = 44), showing worse OS (HR 2.4 95%CI 1.03-5.6 p = 0.042) when treated with Abi/Ez. Conclusions: The nomograns scores showed good correlation with TTF/OS. In PP groups, treatment with Doc was associated with better OS than Abi/Ez, suggesting a possible tool on the first-line decision making.
释疑解惑
Authors: 王学美
Journal: BMJ (2012)

问:在“《高脂血症中医诊疗指南( 2008)》关键内容解读”一文中指出:“临床上要根据患者的危险程度和血脂异常类型决定治疗目标和措施,对于中、低危人群可采取饮食、生活方式及中药综合调理原则,如血脂控制不佳可酌情加入降脂西药”.请问:控制不佳的指标是多少?如何掌握加入西药降脂药的时机?或者说是使用中医药方法干预多长时间血脂仍控制不良就要服用西药?是不是不管干预前血脂多高,都先采取生活方式改变和中药调理。
The value of aspirin in the prevention of colorectal cancer
Authors: Lincheng Yang, Lingyun Zu
Journal: BMJ (2017)

Aspirin has demonstrated its efficacy in the prevention of adverse events related to cardiovascular disease, and lots of epidemiological studies suggest that it also can be used to prevent colorectal cancer and to decrease its recurrence after curative resection. The guideline published by USPSTF recently first time affirms the overall health benefit of aspirin in colorectal cancer prevention. Aspirin could prevent the colorectal cancer by the cyclooxygenase-dependent mechanisms and the COX-independent mechanisms. In this review, we will summarize some results of related researches and discuss the possible mechanisms.


Key words: 
Colorectal neoplasms; Aspirin; Prevention
Immunotherapy and chemotherapy combination for chest wall disease: TBCRC 044 trial.
Authors: Neelima Vidula, Rita Nanda, Kathy Miller, Paula Raffin Pohlmann, Vandana G Abramson, Leisha A. Emens, Ben Ho Park, Minetta C. Liu, Andrei Goga, Hope S. Rugo
Journal: Journal of Clinical Oncology (2020)

TPS1114 Background: Immunotherapy combined with chemotherapy is being studied in metastatic breast cancer, and may have durable outcomes. Chest wall recurrence represents a difficult to treat subtype of breast cancer with a poor prognosis, with lymphovascular invasion in the primary tumor a significant risk factor. Given the inflammatory nature of this disease and the association of programmed cell death 1 (PD-1) expression with lymphovascular invasion, we hypothesized that the combination of pembrolizumab, an anti-PD-1 antibody, with carboplatin may be effective as treatment for breast cancer chest wall recurrences. Methods: This randomized phase II study is enrolling 84 patients with breast cancer involving the chest wall, who may also have distant metastases. Patients receive treatment with pembrolizumab 200 mg and carboplatin AUC 5 every 3 weeks for 6 cycles (Arm A, n = 56) followed by maintenance pembrolizumab +/- carboplatin (Arm Ax), or carboplatin AUC 5 every 3 weeks for 6 cycles (Arm B, n = 28) with an option to cross-over to pembrolizumab +/- carboplatin on progression (Arm Bx). Patients with all disease subtypes, triple-negative, hormone receptor positive/HER2- after 2 prior lines of hormone therapy, and HER2+ disease (with the option to continue trastuzumab) are eligible, with no limit on the number of prior therapies. Prior platinum chemotherapy is allowed in the absence of overt disease progression. Patients undergo clinical assessment with every cycle of treatment including chest wall photography, scans (CT chest, abdomen, and pelvis) every 2 cycles, and have peripheral blood and chest wall biopsies collected at baseline and the start of cycle 3 for correlative studies. The primary endpoint is the disease control rate in the chest wall and distant sites at 18 weeks of treatment based on RECIST 1.1. The study is powered to determine a 20% difference in disease control between arms (hazard ratio 0.52, α = 0.10, β = 0.20). Additional endpoints include response by tumor programmed death ligand 1 (PD-L1) status and irRECIST, progression-free survival, and toxicity. Chest wall tumor samples will be analyzed for changes in tumor immune composition, and PD-L1 and MYC oncogene expression, based on preclinical data to suggest that PD-L1 may be upregulated by MYC. Peripheral blood samples will be evaluated for changes in PD-L1 expression, cell-free DNA, and circulating tumor cells with treatment. The study is enrolling patients at 7 sites within the Translational Breast Cancer Research Consortium (TBCRC), with current enrollment of 38/84 patients. Clinical trial information: NCT03095352 .
Rasing the quality of primary care for gout patients
Authors: Hejian Zou
Journal: BMJ (2020)

近年来，高尿酸血症、痛风已经成为常见的慢性疾病，分级诊疗制度的建设也促使基层医生成为诊疗及管理这类患者的主力军，《痛风及高尿酸血症基层诊疗指南（2019年）》的发布为基层医生规范临床实践提供了参考，本文对该指南中的几个关键点作一补充说明，以帮助基层医生更充分、合理地利用该指南。
口腔保健与义齿性口炎
Authors: 李征, 刘宏伟
Journal: BMJ (2012)

义齿性口炎是指戴可摘义齿者的义齿基托承托区相应黏膜发生的局限性非特异性损害.其主要致病因素是念珠菌感染,此外义齿性口炎的发病还与义齿基托的覆盖范围、口腔卫生习惯等因素相关.预防义齿性口炎的最好方法是培养患者良好的口腔卫生习惯,指导患者掌握正确的义齿清洁方法.治疗义齿性口炎主要使用局部和全身药物治疗。
Surgical operationtreatment for seven cases of severe chronic gouty arthritis
Authors: 张海宁, 王英振, 郝永强, 吕成昱, 王湘达, 刘金钊, 王昌耀
Journal: BMJ (2006)

目的 评价手术治疗慢性严重痛风性关节炎的临床疗效.方法回顾性分析自2003年6月至2005年10月青岛大学医学院附属医院收治的7例严重痛风性关节炎患者,病程8～22年,平均12.2年.2例为单发部位病变,5例为多处受累,受累部位包括跖趾关节、趾间关节、肘关节、踝关节、膝关节、腕关节、掌指关节和指间关节.根据病变严重程度分别采用关节抽吸冲洗类固醇注射、关节镜下病变清理术、痛风病灶清除术、刮除植骨术、Keller's手术及关节融合术治疗痛风病灶.结果术后切口6例一期愈合,1例由于尿酸盐残留延迟愈合.术后随访2个月～2.5年,平均13个月.随访2个月时血清尿酸较术前平均下降48%,5例无高尿酸血症.局部软组织及骨质破坏进程中断;疼痛解除5例,缓解2例;3例植骨术后12个月愈合.手术部位痛风石无复发.5例术后无急性发作,2例在2年内有再次急性发作病史,发作部位为非手术部位,秋水仙碱可控制症状.结论适时手术治疗可及时阻断局部痛风的病理进程,减轻机体总尿酸负荷,有利于提高患者的生活质量和改善其功能。
澳大利亚卫生体系及延伸保健模式的启示
Authors: 李东
Journal: BMJ (2004)

澳大利亚有1 900万人口,是世界上全民保健覆盖面最大、保健服务效果较好的国家之一,在世界卫生组织2000年对191个国家调查中其卫生成就、水平和分布排在第2位,其中卫生系统资金提供公正性指数排第26位(中国第188位)。
Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer.
Authors: Elisa Marie Ledet, Ellen Jaeger, Whitley Hatton, Marcus W. Moses, Alexandra Sokolova, Mari Nakazawa, Jason Zhu, Beth Dellinger, Sara Elrefai, Rana R. McKay, Heather H. Cheng, Earle Frederick Burgess, Emmanuel S. Antonarakis, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2020)

5568 Background: The relevance of germline mutations in metastatic prostate cancer is well established; however, comparison of germline genetics in African American (AA) versus Caucasian (CA) men with metastatic prostate cancer (PCa) is limited. Methods: Germline data from self-identified AA and CA metastatic PCa patients (pts) were collected from 5 academic cancer centers. Various commercial cancer-specific germline testing panels were used to evaluate 12-86 genes. Pathogenic (P) or likely pathogenic (LP) mutations, and variants of unknown significance (VUS), were reported according to ACMG guidelines. Self-reported family history (FH) was annotated for 99% of pts. Statistical analyses included Chi-squared and Fischer’s exact tests. Results: A total of 821 metastatic PCa pts were assessed: 152 AAs and 669 CAs. For P/LP alterations, AAs had a frequency of 11.2% (17/152) as compared to a frequency of 14.6% (98/669) in CAs (p = 0.302). AA pts were more likely to have a VUS than CA pts, 61% vs 43% respectively (OR = 2.09, 95%CI [1.45, 2.99], p &lt; 0.001). BRCA mutations were similar between races, but AA were more likely to have a BRCA1 P/LP alteration (OR = 6.00, 95% CI [1.33, 27.09], p = 0.025). AA pts were less likely to have a P/LP alteration in a non-BRCA gene (OR = 0.34, 95% CI [0.15, 0.80], p = 0.013). Among DNA repair genes, there were no significant difference between AA and CA pts (p = 0.574); however, there was a trend toward AA pts having fewer P/LP alteration in a non-BRCA DNA repair genes (OR = 0.26, 95% CI [0.06, 1.08], p = 0.071). In pts with &gt;1 first degree relative (FDR) with ovarian cancer, P/LP germline alterations were more likely in CAs (OR = 2.33, 95% CI [1.05, 5.17], p = 0.043); but there were no significant differences in AAs (p = 0.098). Those with &gt;2 FDRs with PCa were more likely to have a P/LP change in CAs (OR = 2.32, 95% CI [1.04, 5.15], p = 0.043), but there were no difference in AAs (p = 0.700). In pts with ≥2 FDRs with breast cancer, P/LP germline alterations were more likely in both AAs (OR = 9.36, 95% CI [1.72, 50.84], p = 0.019) and CAs (OR = 3.92, 95% CI [1.79, 8.59], p = 0.001). Conclusions: We did not observe a difference in the overall frequency of germline P/LP alterations between AA and CA men with metastatic PCa but VUSs were more common in AA men. These AA men have an overall frequency of BRCA mutations similar to CA men; however, BRCA1 mutations were more prevalent in these AAs. Non-BRCA P/LP mutations are significantly less frequent in AA pts. A positive family history of &gt;2 FDRs with breast cancer was associated with P/LP alterations in both AA and CA pts.
Systemic delivery of peptides by the oral route: Formulation and medicinal chemistry approaches
Authors: D.J. Brayden, T.A. Hill, D.P. Fairlie, S. Maher, R.J. Mrsny
Journal: Advanced Drug Delivery Reviews (2020)

In its 33 years, ADDR has published regularly on the po5tential of oral delivery of biologics especially peptides and proteins. In the intervening period, analysis of the preclinical and clinical trial failures of many purported platform technologies has led to reflection on the true status of the field and reigning in of expectations. Oral formulations of semaglutide, octreotide, and salmon calcitonin have completed Phase III trials, with oral semaglutide being approved by the FDA in 2019. The progress made with oral peptide formulations based on traditional permeation enhancers is against a background of low and variable oral bioavailability values of ~1%, leading to a current perception that only potent peptides with a viable cost of synthesis can be realistically considered. Desirable features of candidates should include a large therapeutic index, some stability in the GI tract, a long elimination half-life, and a relatively low clearance rate. Administration in nanoparticle formats have largely disappointed, with few prototypes reaching clinical trials: insufficient particle loading, lack of controlled release, low epithelial particle uptake, and lack of scalable synthesis being the main reasons for discontinuation. Disruptive technologies based on engineered devices promise improvements, but scale-up and toxicology aspects are issues to address. In parallel, medicinal chemists are synthesizing stable hydrophobic macrocyclic candidate peptides of lower molecular weight and with potential for greater oral bioavailability than linear peptides, but perhaps without the same requirement for elaborate drug delivery systems. In summary, while there have been advances in understanding the limitations of peptides for oral delivery, low membrane permeability, metabolism, and high clearance rates continue to hamper progress.
Management time for patients with acute cerebrovascular disease before and after re-accreditation of Grade III Class A in a general hospital
Authors: Shan Jiang, Cheng Jiang, Yan Zhao
Journal: BMJ (2017)

Objective
To compare the change of management time for patients with acute cerebrovascular disease before and after re-accreditation of Grade Ⅲ Class A in a general hospital.


Methods
Electronic medical records of 490 patients diagnosed as acute cerebrovascular disease(215 cases of cerebral infarction, 275 cases of cerebral hemorrhage) managed in Zhongnan Hospital of Wuhan University from June 2015 to July 2016 were collected, including 262 patients managed before re-accreditation (group A, June 2015 to December 2015) and 228 patients admitted after re-accreditation (group B, January 2016 to July 2016). In group A, there were 109 cases of cerebral infarction and 153 cases of cerebral hemorrhage(68 caused by trauma); in group B there were 106 cases of cerebral infarction and 122 cases of cerebral hemorrhage(54 caused by trauma). The time in emergency department (ED time), time waiting for admission (admission time) and the total management time (total time) were analyzed and compared between two groups.


Results
The ED time in group A and group B was 44.5(30.0, 71.5)and 39.0 (20.3, 69.0) min(Z=-2.103, P=0.036) respectively; the admission time was 35.0(25.8, 50.0)and 39.0(27.3, 55.8) min(Z=-2.211, P=0.027); and total time was 85.0(62.8, 120.0)and 82.5(61.0, 119.0) min(Z=-0.356, P=0.722) in two groups respectively.For patients of cerebral infarction in group A and B the ED time was 49.0(33.5, 81.5)and 41.0(29.8, 74.3) min(Z=-1.872, P=0.061); the admission time was 37.0(27.0, 52.0)and 36.0(25.0, 52.3) min(Z=-0.516, P=0.606); and total time was 97.0(69.5, 131.0)and 83.5(62.0, 118.3) min(Z=-1.914, P=0.056). For patients of cerebral hemorrhage in group A and B, the ED time was 42.0(28.0, 64.0)and 35.0(17.8, 65.0) min(Z=-1.426, P=0.154); the admission time was 34.0(24.5, 49.0)and 41.0(31.0, 61.0) min (Z=-3.353, P=0.001); and total time was 79.0(58.0, 108.0) and 82.0(60.0, 120.8) min(Z=-1.052, P=0.293).


Conclusions
After re-accreditation of Grade Ⅲ Class A Hospital the total waiting time for patients of cerebral infarction is decreased significantly in emergency department, however, for patients of cerebral hemorrhage the waiting time for admission is longer.


Key words: 
Medical records systems, computerized; Cerebrovascular disorders, acute; Hospital, general; Peer review, health care