tbuckley/cabot-search huggingface dataset:
Results from the safety lead-in for a phase II study of pembrolizumab in combination with binimetinib and bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).
Authors: Christopher Hanyoung Lieu, Sarah Lindsey Davis, Stephen Leong, Alexis Diane Leal, Patrick Jud Blatchford, Gurprataap Singh Sandhu, William T. Purcell, Sunnie S. Kim, Zoe Van De Voorde, Rachel Telles, Anne Martin, Tiffany Cull, Meredith Waring, Colin Reed, Chimmoua Lee, Amanda Siedem, Matthew R Lee, Todd Pitts, S. Gail Eckhardt, Wells A. Messersmith
Journal: Journal of Clinical Oncology (2020)

4031 Background: The majority of pts with mCRC have microsatellite stable (MSS) tumors with minimal response to PD-L1/PD-1 blockade. MEK inhibition and VEGF inhibition have immunomodulatory effects (upregulation of tumor major histocompatibility complex-I expression, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors) supporting clinical evaluation of combined MEKi (B), anti–PD-1 (P), and anti-VEGF (BV) in pts with mCRC. We hypothesize that the combination of binimetinib, pembrolizumab, and bevacizumab (BPBV) will result in greater clinical benefit than pembrolizumab alone. Methods: Patients with chemotherapy-refractory mCRC were evaluated (20 planned in the safety lead-in and 50 planned for total accrual). B was dosed at 45mg PO BID, P was administered at 200mg IV Q21 days, and BV was administered at 7.5mg/kg IV Q21 days. Primary objectives were safety, tolerability, and investigator-assessed ORR by RECIST 1.1. Clinical benefit rate (CR+PR+SD) and progression-free survival were secondary endpoints. Descriptive statistics were used to summarize safety and clinical activity. Results: As of January 9, 2020, 21 pts (10 KRAS/NRASmt, 11 RASwt, 21 MSS) were enrolled into the safety lead-in and were evaluable. The median number of prior therapies was 6. The BPBV combination was tolerable. Treatment-related Gr 1-2 and Gr 3-4 AEs occurred at 60% and 38%, respectively. The most frequent related Gr 3-4 AEs were aceniform rash, diarrhea, and hypertension (19%, 14%, 14% respectively). No treatment-related Gr 5 AEs occurred. A total of 17 patients were evaluable for response. Confirmed PR was observed in 2 pts (12%). SD was noted in 14 patients (82%) leading to a clinical benefit rate of 94%. 1 patient had PD as the best response to treatment. Median PFS was 6.4 months (95% CI 4.2-8.9). Molecular determinants, immune biomarkers, and updated tumor assessments of response will be presented. Conclusions: B + P + BV demonstrated a tolerable safety profile and improvements in ORR and clinical benefit rate compared to those reported with SOC in heavily pretreated pts with mCRC. Objective responses observed in pts were durable, suggesting benefit of this novel combination in a patient population refractory to immune therapies. Clinical trial information: NCT03475004 .
High serum sPD-1 and sPD-L1 levels 1 predict outcome in hepatocellular carcinoma patients treated with radiotherapy.
Authors: Shisuo Du, Genwen Chen, Yixing Chen, Ping Yang, Yong Hu, Qianqian Zhao, Zhao-Chong Zeng
Journal: Journal of Clinical Oncology (2020)

e16672 Background: Accumulating data have shown that soluble (s)PD-1 and sPD-L1 are potential biomarkers for the curative efficacy of chemotherapy in several cancers. However, these markers have not been well established for outcomes in hepatocellular carcinoma (HCC) radiotherapy (RT). Therefore, this study aims to assess sPD-1/sPD-L1 levels before and after RT and their relationship to clinical characteristics and prognoses. Methods: Pre-treatment serum sPD-L1 and sPD-1 levels were measured with an enzyme-linked immunosorbent assay (ELISA) in 281 patients with HCC treated with RT. The association between serum sPD-L1 and sPD-1 levels and prognosis was assessed using survival analysis. Formalin-fixed paraffin-embedded samples were obtained from 40 patients with HCC who underwent surgery. The expression of PD-L1 was evaluated by immunohistochemical analysis. Results: Using multivariate analyses; sPD-L1 and sPD-1 levels were significant independent predictors of disease-free and overall survival. Patients with maximum tumor diameters ≥5 cm and Barcelona clinic liver cancer (BCLC) staging B and C had significantly higher median sPD-1/sPD-L1 serum concentrations compared to patients with smaller tumor sizes and earlier stages. There was a positive correlation (r = 0.377, p &lt; 0.001) between sPD-L1 and sPD-1 levels. High pretreatment sPD-1/sPD-L1 levels were associated with poor prognoses, and increased sPD-1/sPD-L1 levels were associated with disease progression after RT. In post-irradiated tumor tissue, PD-L1 expression was significantly higher than matched, non-irradiated tissue. In addition, higher PD-L1 expression was correlated with decreased cytotoxic T-cell infiltration and poor survival. Therefore, sPD-1/sPD-L1 could be used as noninvasive biomarkers for evaluating HCC malignancy before RT and in predicting the response to RT in HCC patients. Conclusions: High pretreatment serum sPD-L1 and sPD-1 were associated with poor prognoses, and increased serum sPD-L1 levels were associated with the disease progression of HCC patients treated with RT. PD-L1/ PD-1 pathway may be explored as therapeutic targets and potential predictive biomarkers for HCC treated with RT.
Results of the first round of a demonstration pilot of screening for colorectal cancer in the United Kingdom
Authors: 胡恩坦
Journal: BMJ (2004)

目的：
评价在英国国家医疗体系（National Health Service，NHS）中推行以便隐血试验为基础的全国大肠癌筛查项目的可行性。


研究设计：
预试验。


场所设置：
英格兰的2个医疗权威机构和苏格兰的3个医疗部门。


研究对象：
年龄为50~69岁的人群。


结果：
邀请试验地区的478 250位居民参与此次筛查项目，最终有便隐血试验结果的共271 646人（占56.8%）。总阳性结果率为1.9%，而大肠癌检出率为1.62‰。以上两种指标在苏格兰地区高于英格兰地区；男性高于女性，并且随年龄的增加而增高。大肠癌与大肠腺瘤发生的阳性预测值分别为10.9%和35.0%。筛查中一共发现大肠癌病例552例；其中92例（16.6%）为息肉癌。所有检出的癌症病例中48%Dukes分期为A期，1%在诊断时已经发生转移。


结论：
在英国国家医疗服务体系中利用便隐血试验对大肠癌进行筛检是可行的，能减少受检人群因大肠癌导致的死亡。
Inpatient mortality, healthcare resource utilization, and complications of elective laparoscopic versus open colectomy in colon cancer patients: A nationwide inpatient sample analysis.
Authors: Ishaan Vohra, Vatsala Katiyar, Bashar Attar, Prasanth Lingamaneni, Krishna Rekha Moturi, Sunny R K Singh, Sindhu Janarthanam Malapati, Muhammad Zain Farooq, Shweta Gupta
Journal: Journal of Clinical Oncology (2020)

4109 Background: Laparoscopic colectomy (LC) has become an accepted safe and alternative technique to open surgical colectomy (OC) as a treatment option for colon cancer. We compared inpatient mortality, hospital resource utilization and complications in patients who underwent LC vs OC. Methods: All patients with known diagnosis of colon cancer who underwent elective colonic resection were identified using Nationwide Inpatient Sample (NIS) 2017. Univariate and multivariate linear and logistic regression was performed to compare the outcomes of patients who underwent LC vs OC. Results: In our cohort, 171, 480 adult patients with colon cancer were identified. The number of males and females were equal. The mean age was 67.2 years. They were predominantly Caucasians (67.6%). OC was performed on 3,869 patients. Of 1,345 patients who underwent LC, 385 were converted to OC. As compared to OC, LC was associated with lower postoperative complications including anastomotic leak, stricture, intestinal obstruction(1% vs 10.8%, p&lt;0.01), blood transfusion(2.2 % vs 11.2% p=0.01), malnutrition(0.2% vs 4.4% p=0.02), shock(0.7% vs 1.8%,p=0.04), ICU care(1.9% vs 5.3%), mean length of stay (5.9 days vs 8.7 days, p=0.01), lower hospital charge (88,642$ vs 106,315 $,p&lt;0.01) and lower mortality(0.3% vs 1.9%(p=0.02). There was a trend towards decreased venous thromboembolism (0.3% vs 1.7 %, p=0.9) and post-operative ileus (0.1% vs 0.7% p=0.60) in LC as compared to OC. On multivariate analysis, independent predictors of undergoing LC were younger age, teaching and large bed-sized hospital and lower Charlson comorbidity index. Race, insurance status and income had no significant association with selection of operative approach (Table). Conclusions: In our cohort, laparoscopic colectomy was found to have better peri and post-operative clinical outcomes including decreased inpatient mortality and hospital resource utilization. It should be promoted as the curative surgical option for colon cancer whenever clinically indicated. [Table: see text]
抗心磷脂抗体与梅毒感染关系的研究进展
Authors: 任荣鑫, 张海萍
Journal: BMJ (2012)

抗磷脂抗体是一种自身免疫抗体,目前主要应用于抗磷脂综合征及某些自身免疫病的诊断中.国内有学者应用ELISA方法检测梅毒患者血清中的抗心磷脂抗体,以期替代非梅毒螺旋体抗原血清学试验快速诊断梅毒.笔者就抗心磷脂抗体的分类和检测方法,分析导致检测结果不一致的原因。
Comprehensive prevention and management of chronic obstructive pulmonary disease in primary care in UK
Authors: Ming Yang, Chunhua Chi
Journal: BMJ (2017)

慢性阻塞性肺疾病(慢阻肺)是呼吸系统的一种常见病和慢性病，良好的社区管理及家庭自我管理对延缓病情进展和避免病情急性加重具有重要作用。英国社区医疗发展较为健全，有较为完善的社区慢阻肺防治网络及规范的防治指南，通过对英国社区慢阻肺的综合防治策略进行概述，以期为国内社区开展慢阻肺防治工作提供参考和借鉴。
Risk of recurrence in patients with HER2+ breast cancer who achieved a pathological complete response (pCR) after neoadjuvant pertuzumab and trastuzumab (nPT), and received adjuvant trastuzumab (aT): Real-world evidence.
Authors: Nicholas J. Robert, Joyce O'Shaughnessy, Srinivas Annavarapu, Jie Zhou, Jesse Sussell, Anna Cheng, Anita Fung
Journal: Journal of Clinical Oncology (2020)

e12648 Background: The real-world risk of disease recurrence in patients with HER2+ early breast cancer who achieved pCR after receipt of nPT-based regimens and aT is unclear. Methods: Women with HER2+ breast cancer who achieved pCR after nPT-based regimens and received aT were identified in the US Oncology Network (USON). Patients initiated nPT between 2013 –2015 and were followed until recurrence of invasive disease or censoring. Data was sourced from structured fields and review of USON patient charts. Recurrence of invasive disease was defined as any of: recurrence of ipsilateral locoregional invasive breast cancer, contralateral breast cancer, distant disease recurrence, or death. Descriptive analyses were used to assess baseline demographic and clinical characteristics and the Kaplan-Meier method was used to assess invasive disease-free survival (iDFS), with stratification by nodal status. Results: A total of 238 pCR patients’ charts were reviewed. Median patient age was 52 (range: 23-88) years and a majority were White (77%). Most patients had stage IIA (39%) or IIB (24%) disease at diagnosis, ECOG score &lt; 1 (85%), and tumor size &gt; 2 cm (68%). At diagnosis, the majority of patients (57%) were node positive (N+) and negative for estrogen or progesterone receptor expression (51%). Median durations of therapy for nPT and aT were 4 (range: 1-8) and 7 (range: 0.03-53) months, respectively. The median duration of follow up was 47 (range: 1-70) months. Four-year iDFS probabilities are shown in the Table. Conclusions: Consistent with previously reported clinical trial data and several pooled analyses, results from this real-world study indicate that despite achieving pCR after nPT-based regimens, patients with HER2+ BC remain at risk for disease recurrence; in addition, node+ status appears to increase that risk. Therefore, patients should receive standard pertuzumab, trastuzumab adjuvant therapy to optimize treatment outcomes. [Table: see text]
Patient and Study Participant Rights to Privacy in Journal Publication
Authors: Annette Flanagin, Howard Bauchner, Phil B. Fontanarosa
Journal: JAMA (2020)

Personal health information is defined as identifiable data related to the past, present, or future health status of an individual. 1 Personal health information has been considered protected health information, which is governed by ethical principles and laws to shield against intrusions into an individual's rights to privacy.2][3] As Gostin and colleagues have warned, "Individuals' health data are now solicited, aggregated, analyzed, shared, and sold in ways poorly understood and largely unregulated." 1 Clearly, new or enhanced legislative privacy safeguards are needed to protect personal health information.The right to privacy for personal health information also extends to reports in scientific and clinical publications.When patients and study participants grant authors and researchers access to personal information during a patientclinician or participant-investigator encounter, they allow access to personal information but do not waive all such rights. 4During and following these encounters, privacy and confidentiality should be maintained, and identifiable personal information should not be made public via publication without consent.Authors and editors should ensure proper reporting of ethical protections of patients and research participants in scholarly publications. 5This includes following the principles of ethical review and approval of research and informed consent, or waiver or exemption thereof.This also includes protection of patients and research participants' rights to privacy in scholarly publication by withholding or removing identifiable personal health information from content submitted to journals unless permission for publication has been provided. [5]6][7][8][9] Such content includes descriptions in text, demographic data in tables, detailed test results, photographs and other digital images, genetic pedigrees, other detailed data displays, video, and audio.
Statins and chronic heart falure
Authors: 刘洋, 赵明中
Journal: BMJ (2006)

心力衰竭(heart failure,HF)是各种心脏病发展至晚期或终末期的结果,是最常见的严重危害人类生命健康的心血管疾病.众多研究表明,在多种疾病发展为HF和加重的过程中,常伴有血管内皮功能异常、氧化应激过度、神经内分泌的激活、多种炎症细胞因子参与和心室重构.所以对造成HF的各个阶段分别进行有效的干预,防止病变进展,可降低人群HF的发病率和病死率。
Adoption of opportunistic salpingectomy for ovarian cancer prevention: Results from a nationwide sample of privately insured women.
Authors: Pritesh S Karia, Corinne E Joshu, Neil B. Rosenshein, Kala Visvanathan
Journal: Journal of Clinical Oncology (2020)

1561 Background: Recent evidence indicates that the Fallopian tube is the site of origin for many high-grade serous ovarian cancers, particularly in BRCA carriers. This has led to the emergence of opportunistic salpingectomy (OS) as a novel ovarian cancer prevention strategy. Despite limited data, some national societies now recommend OS for ovarian cancer prevention during benign hysterectomy or in place of tubal ligation for sterilization in average-risk women. We assessed patient characteristics associated with increased likelihood of OS and national trends in OS adoption before and after release of recommendations. Methods: Data from MarketScan were used to identify women who underwent hysterectomy, tubal ligation, and OS from 2010-2017. Rates of OS were compared and interrupted time series analysis with segmented Poisson regression was used to examine immediate and persistent changes in OS rates before and after recommendations. Rates were calculated quarterly and models were adjusted for age and seasonality. Results: A total of 309,574 tubal ligations, 13,574 OS for sterilization, 293,000 hysterectomies, 22,798 hysterectomies with OS were included. Quarterly rates of OS for sterilization and hysterectomy with OS were 3.13 and 4.82 per 100,000 women, respectively. About 92% of OS for sterilization and 56% of hysterectomy with OS were performed in women &lt; 45 years. The most common indication for hysterectomy with OS was uterine fibroids (46%). About 8% of OS for sterilization and 10% of hysterectomy with OS were performed in women with a family history of breast or ovarian cancer. After adjusting for age and seasonality, there was a 250% immediate increase (RR: 3.50; 95% CI: 2.59-4.72) followed by a 14% (RR: 1.14; 95% CI: 1.10-1.18) persistent increase in the quarterly rate of OS for sterilization after versus before recommendation release. There was a 109% immediate increase (RR: 2.09; 95% CI: 1.15-3.81) in the quarterly rate of hysterectomy with OS after versus before recommendation release. No persistent change in the rate of hysterectomy with OS was observed. Significant declines in hysterectomy and tubal ligation rates were observed and these declines were temporally associated with the release of recommendations. Conclusions: OS for ovarian cancer prevention has rapidly diffused into clinical practice with the speed of adoption bolstered by recommendations from national societies. Future studies evaluating the overall efficacy and long-term complications of OS are needed to support its continued widespread use.
Prenatal ultrasound diagnosis of fetal choledochal cysts
Authors: Luyan Yu, Bo Hu
Journal: BMJ (2016)

Objective
To assess the application of ultrasonography in prenatal diagnosis of fetal choledochal cysts.


Methods
The clinical data of 25 fetuses, who were diagnosed as fetal choledocho cysts using ultrasonography and followed up, were retrospectively analyzed.


Results
Among 25 cases, 24 cases were confirmed as congenital choledochal cysts after normal delivery or abortion, and 1 case of liver cyst was misdiagnosed. The 24 cases′ prenatal ultrasound showed liver cystic space occupying wihich was connected to intrahepatic bile duct or gallbladder.The cysts wall was thin, and the colour Doppler flow imaging CDFI showed that blood vessels circled around the cyst.In 24 fetuses with prenatal choledochal cysts, 21 were full-term birth, 3 were aborted including 1 case with other congenital abnormalities. The size of choledochal cysts was not changed in 5 cases, and was enlarged with the gestational ages in remaining 16 cases fetuses. The choledochal cysts did not affect fetal growth and development. The newborn infants with congenital choledochal cysts were treated surgically within 8 months after birth and all recovered well.


Conclusion
Fetal choledochal cysts have typical sonographic manifestations.Ultrasonography can be used for prenatal diagnosis of congenital choledochal cysts, which can be successfully treated by surgery early after birth.


Key words: 
Prenatal ultrasonography; Fetus; Choledochal cyst; Intrauterine growth; Prognosis
Comparison of pathological features of estrogen receptor-positive/HER2-negative early breast cancer in the intermediate-risk group of the 21 gene recurrence score (Oncotype Dx) divided into low and high-risk groups by the 95 gene classifier (Curebest 95GC Breast).
Authors: Yoshihiko Kamada, Seiko Tsuchiya, Naoko Takigami, Kentaro Tamaki, Kanou Uehara, Nobumitsu Tamaki
Journal: Journal of Clinical Oncology (2020)

e12535 Background: Oncotype Dx is becoming the standard assay for chemotherapy decision making for estrogen receptor positive / HER2 negative early breast cancer. Issues concerning the choice of therapy for the intermediate risk patients are currently being addressed. We are using a 95-gene classifier developed by Osaka University and Sysmex Corporation (Curebest 95 GC Breast) which divides patients into "low" and "high" risk groups, which obviates this issue. In this study, we analyzed the histopathological characteristics of low and high risk patients by the 95-gene classifier that would be classified as intermediate risk by 21-gene-recurrence score (21RS). Methods: Fresh tissue samples collected at surgery was sent for 95-GC analysis. Cel-files containing the gene expression data of each sample was uploaded to Recurrence Online (recurrenceonline.com) and the 21-RS was obtained. Histopathological analysis of the tumor specimens including the pathological tumor size, degree of tumor infiltrating lymphocytes ("TIL"s) (0, 1+, 2+, 3+), nuclear pleomorphism (NP score 1, 2, 3), and number of mitoses (M score 1, 2, 3) was done. The age of the patient and the Ki-67 percentage of the preoperative biopsy specimen was also noted. Results: There were a total of 38 cases. The cases with a matching 21RS and 95GC "Low" (Group L-L) was 10, a matching "High" (Group H-H) was 15, 21RS "Intermediate / 95GC "Low" (Group I-L) was 4, 21RS "Intermediate / 95GC "High" (Group I-H) was 7, and discordant 21RS "High" / 95GC "Low" (Group H-L) was 2, respectively. There was no age related differences (average 53.3 y.o.). There was a significant difference between the L-L and H-H groups in all categories (i.e. pT 14.5 mm v.s. 30.0 mm / p = 0.0262, NP score average 2.1 v.s. 2.5 / p = 0.287, M score average 1.2 v.s 2.4 / p &lt; 0.001, TILs average 0.4+ v.s. 1.2+ /p = 0.0413, Ki67 25.0% v.s. 33.2%). The trend was the same between the I-L and I-H group with the exception of the mitosis score, which showed an inverse trend of a high of 2.25 in the I-L v.s. low of 1.43 in the I-H group (p = 0.9522). The H-L group had high NP score (average 3.0), low M score (average 1.0), and high TILs (average 2+). Conclusions: The 95-gene classifier might be more sensitive compared to 21RS in picking up histio-morphological information, and also may be able to differentiate the type of immune response of TILs. We are planning further immunohistological evaluation.
《中国高血压防治指南2010》要点介绍(一)
Authors: 李瑞杰
Journal: BMJ (2012)

《中国高血压防治指南2010》[1](下简称新指南)是在2005年版《中国高血压防治指南》的基础上,根据我国心血管病流行趋势和循证医学研究的进展,并参考国内外最新研究成果和各国指南,广泛征求意见,由近百位中国专家集体讨论和编写,历时2年完成的。
CD4+ and CD8+ cytotoxic T lymphocytes may induce mesenchymal cell apoptosis in IgG4-related disease
Authors: Cory A. Perugino, Naoki Kaneko, Takashi Maehara, Hamid Mattoo, Jesper Kers, Hugues Allard-Chamard, Vinay S. Mahajan, Hang Liu, Emanuel Della-Torre, Samuel J.H. Murphy, Musie Ghebremichael, Zachary S. Wallace, Marcy B. Bolster, Liam M. Harvey, Geetha Mylvaganam, Yesim Tuncay, Lloyd Liang, Sydney B. Montesi, Xiuwei Zhang, Akira Tinju, Keita Mochizuki, Ryusuke Munemura, Mizuki Sakamoto, Masafumi Moriyama, Seiji Nakamura, Nir Yosef, John H. Stone, Shiv Pillai
Journal: Journal of Allergy and Clinical Immunology (2020)
Symptoms, psychosomatic factors and autonomic nervous function in patients of gastroesophageal reflux disease
Authors: 王大冰, 王世喜, 刘安民, 韩玉娟, 韩芝, 刘英
Journal: BMJ (2007)

目的 探讨胃食管反流病(GERD)患者临床症状、心身因素、自主神经功能之间的关系.方法 15例对照者与34例经反流性疾病诊断问卷(RDQ)及经过内镜检查诊断为GERD的患者,均填写Zung自评量表,评分异常的GERD患者为GERD(+)组,评分正常的GERD患者为GERD(-)组,两组同时记录反流症状积分.全部入选者均进行心率变异性检查.检测频域:24 h内平均R-R间期的标准差,5 min平均窦性心率标准差,相邻R-R间期之差的均分根,相邻心搏R-R间期之差大于50 ms的心搏占心搏总数的百分比.时域:低频,高频,低频/高频.结果 GERD组Zung焦虑自评量表平均分、Zung抑郁自评量表平均分明显高于对照组(分别为48±9对38±6,48±11对41±6,均P＜0.05).GERD(+)组Zung分数与症状积分呈正相关,相关系数为0.411和0.483.同时发现非糜烂性反流病组Zung评分异常分布.GERD患者迷走神经张力较对照组增高,GERD(+)组增高更明显.结论 GERD患者尤其是非糜烂性反流病患者反流症状、心身因素、自主神经功能之间互相影响、互为因果,自主神经功能紊乱可能是中间环节.对GERD患者需整体治疗。