tbuckley/cabot-search huggingface dataset:
JAK2V617F mutant-positive polycythemia vera complicated with acute coronary syndrome: a report of 2 cases and literature review
Authors: Fengjing Liang, Xiang Xiao, Ting Xiao, Chaoyong Xiao, Wen Liu, Zhou Xiao, Xue Chai, Bing Zou, Jiying Shen, Ting Qiu
Journal: BMJ (2014)

Objective
To review the clinical features, diagnosis, prognosis and treatment of polycythemia vera(PV)complicated with acute coronary syndrome(ACS).


Methods
The clinical data of 2 PV patients complicated with ACS admitted to Peking Union Medical College Hospital (PUMCH) were retrospectively analyzed and the recent literatures were reviewed.


Results
Case 1 was a 65-year old man who had been diagnosed PV with a positive JAK2V617F mutation 3 years ago. At presentation, the patient was suffering from recurrent angina pectoris, and coronary angiography revealed that there was a severe(80%)stenosis in the middle segment of left circumflex and a Xience V stent was implanted. After the percutaneous transluminal coronary intervention (PCI), secondary prevention for coronary heart disease and hydroxyurea for PV were given and the patient has been followed up regularly for more than three years and he is going well. Case 2 is a 44-year old man who was diagnosed PV with a positive JAK2 mutation 3 years ago and hydroxyurea, interferon, aspirin was prescribed. Then splenic infarction, thrombosis of splenic vein, regional portal hypertension, severe varices of fundus of stomach and upper gastrointestinal bleeding developed with him. Two months ago, an AMI of inferior wall occurred and the angiographic findings demonstrated an thrombotic lesion in the proximal segment of the right coronary artery with a moderate stenosis (60%); 1 month ago an AMI of anterior wall developed and coronary angiography discovered that there were diffuse thrombus in the proximal segment of left anterior descending artery with a severe stenosis (90%) and a complete occlusion in the right coronary artery. After double antiplatelet therapy with anticoagulation therapy of warfarin was given, the patient recovered gradually.


Conclusions
PV complicated with ACS is relatively rare. According to recent studies, positive JAK2V617F mutation, leukocytosis, age>65 years and positive history of thrombosis are the most important predictors of cardiovascular events. Clinicians should design individualized treatment strategies for patients on the basis of clinical features, coronary angiography findings and complications. For those with thrombotic lesion in the coronary artery due to the hypercoagulative state caused by PV, it should be cautious to carry out a coronary revascularization treatment.


Key words: 
Vera polycythemia; Coronary disease; Review literature
Measuring tools for patient-centered care in general practice
Authors: Chen Sun
Journal: BMJ (2016)

General practice has been developed for almost 30 years in China, while how to measure the patient-centered care in general practice is still under exploration. In this article we review the application and development of the assessment tools of patient-centered care both in foreign country and in China, so that to provide reference for the development of measuring tools of patient-centered care in general practice suitable for Chinese conditions.


Key words: 
General practitioners; Assessment tool; Patient-centered care
发热-巩膜炎-皮疹-神志异常
Authors: 包扬, 沈敏, 曾学军
Journal: BMJ (2012)

患者男性,63岁,因反复发热1年余,皮疹伴神志障碍5d,于2011年10月9日入北京协和医院.患者于2010年9月中旬无明显诱因出现发热,最高温度39℃,以午后及夜间为著,无畏寒、寒战,发热时伴头晕. 关键词：红斑狼疮;系统性
ZW25, an anti-HER2 bispecific antibody, plus chemotherapy with/without tislelizumab as first-line treatment for patients with advanced HER2-positive breast cancer or gastric/gastroesophageal junction adenocarcinoma: A phase 1B/2 trial-in-progress.
Authors: Do-Youn Oh, Hyun Cheol Chung, Young Hyuck Im, Chia Jui Yen, Yee Chao, ZheZhen Li, Xin Wang, Jin Wang, Huiyan Li, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2020)

TPS3145 Background: ZW25 is a novel HER2-targeted antibody that binds two distinct extracellular domains of HER2, allowing for multiple mechanisms of action, including activation of ADCC and inhibition of ligand-dependent and -independent cellular growth. ZW25 is well tolerated and showed single-agent antitumor activity in patients (pts) with advanced HER2-positive cancers. Previous reports suggested that tislelizumab, an investigational anti-PD-1 antibody engineered to minimize binding of FcgR on macrophages in order to abrogate antibody-dependent phagocytosis, was generally well tolerated and had antitumor activity alone and in combination with chemotherapy in pts with advanced solid tumors. Combining HER2-targeted agents with chemotherapy has resulted in improved survival; the highly immunogenic nature of HER2 tumors has led to the development of therapies combining anti-HER2 therapies with immune checkpoint blockade. Methods: This open-label, two cohort phase 1B/2 study is designed to evaluate ZW25 plus chemotherapy ± tislelizumab as first-line therapy in pts (n≈50) with HER2-positive metastatic breast cancer (mBC; cohort 1) or advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC; cohort 2). In cohort 1, pts with HER2-positive (IHC3+ or ISH amplified) mBC must be treatment-naïve for metastatic disease and will receive intravenous (IV) ZW25 30 mg/kg plus docetaxel 75 mg/m 2 IV once every 3 weeks (Q3W). In cohort 2, treatment-naïve pts with HER2-positive (IHC3+ or IHC2+ with ISH amplification) advanced GC/GEJC will receive ZW25 30 mg/kg plus tislelizumab 200 mg IV and chemotherapy (CAPOX regimen: capecitabine 1000 mg/m 2 twice daily and oxaliplatin 130 mg/m 2 IV) Q3W. A safety lead-in phase is designed for the first six pts in cohort 2, followed by dose expansion after a safety monitoring committee review. Primary endpoints are the safety/tolerability profile and objective response rate; secondary endpoints include duration of response, time to response, progression-free survival, disease control rate, and overall survival. Clinical trial information: Registered, NCT number pending will provide as soon as available .
Cardiac function of patients with chronic obstructive pulmonary disease evaluated by echocardiography
Authors: Weichun Mo, Zhihua Zhang, Wei Wang, Fengya Zheng, Xi Zhang, Jie Shen
Journal: BMJ (2016)

Objective
To evaluate the cardiac function in patients with chronic obstructive pulmonary disease (COPD) by using echocardiography.


Methods
Three hundred and twenty eight COPD patients and 60 age and gender-matched healthy subjects (control group) were enrolled in the study. According to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, patients were as classified as mild (n=102), moderate (n=85), severe (n=80) and very severe (61). All participants underwent conventional echocardiography and two dimensional-speckle tracking echocardiography (2D-STE) to assess cardiac function.


Results
The LVEF was reduced significantly, while the PASP was increased in severe and very severe COPD patients [(60.9±2.0)% and (59.4±2.8)%, t value: 3.358, 4.859 to normal controls, 5.247, 6.641 to mild, 3.280, 4.863 to moderate, respectively, all P<0.001]. The LA size was dilated in very severe COPD patients [(3.9±0.5)cm, t value:-2.407,-2.625,-2.071,-2.186, P<0.05], and the RVEF was significantly less than those of the other patients [(42.8±7.3)%, t value: 6.357, 6.832, 5.581, 4.639, P<0.05]. The right ventricular FAC of moderate or severe COPD patients and the segmental and global LS of left and right ventricular in COPD patients were significantly lower than those in the normal controls, and which were gradually decreased as GOLD classification rising [RVFAC, moderate: (37.7±2.0)%, severe: (35.5±3.2) %, very severe: (34.0±3.1) %, t value:-4.616,-5.982,-7.195, respectively; LSLVg, moderate: (-18.62±1.76) %, severe: (-17.15±0.73) %, very severe: (-16.51±0.89) %, t value: -9.389,-15.494,-16.873, respectively; LSRVg, moderate: (-20.52±2.27) %, severe: (-18.84±1.38) %, very severe: (-16.82±1.10) %, t value: -8.555,-13.595,-18.499, respectively, all P<0.001]. Besides, the FAC of COPD patients was positively correlated with the RVEF (r=0.676, P<0.05), while the RVLSg was negatively correlated with the FAC and RVEF (r=-0.677,-0.591, all P<0.05).


Conclusions
There were left and right ventricular dysfunction in COPD patients, which decreased as GOLD classification upgraded. The FAC and 2D-STE can effectively detect the subtle abnormalities of regional and global ventricular function.


Key words: 
Pulmonary disease, chronic obstructive; Ventricular function; Echocardiography
lncRNA, <i>PVT-1,</i> controls tumorigenesis and cancer stem-like phenotypes in osteosarcoma through PI3K/TSC2.
Authors: Susan Tsang, Nino Carlo Rainusso, Jason Todd Yustein
Journal: Journal of Clinical Oncology (2020)

e23512 Background: Osteosarcoma is the most common pediatric bone cancer and a key genetic characteristic of this particular malignancy is its complex karyotype. Specifically it has been reported that 40% of osteosarcoma patients’ present with 8q24 amplification. The presence of this specific amplification has been previously associated with a high rate of relapse and poor prognosis for osteosarcoma patients. Within this amplicon resides, a long non-coding RNA gene, PVT-1. Prior studies indicates that PVT-1 has pro-oncogenic properties however the function of PVT-1 in osteosarcoma is not well characterized. Methods: To understand PVT-1 copy number, Fluorescent In Situ Hybridization was performed on both osteosarcoma cell lines and osteosarcoma patient-derived xenografts. In addition the PVT-1 RNA level is elevated in a majority of osteosarcoma samples compared to normal bone. To test PVT-1 pro-oncogenic role in osteosarcoma, several functional assays were performed. Results: Our studies demonstrated that overexpression of PVT-1 in osteosarcoma cell lines promotes multiple tumorigenic behaviors including enhanced proliferation, migration, invasion and chemotherapeutic resistance to cisplatin. PVT-1’s ability to mediate metastasis and contribute to chemotherapeutic sensitivity is a shared phenotype of cancer stem cells. Based on this observation, we hypothesize targeting PVT-1 will reduce cancer stem-cell properties. Osteosarcoma lines with increased levels of PVT-1 exhibited higher expression of cancer stem cell genes: Nanog, SOX2, c-Myc, and Oct4 at both the transcriptomic and proteomic level. In Vitro and In Vivo self-renewal capacity studies showed enhanced osteosarcoma cell self-renewal in the PVT-1 overexpression cohort. Additional molecular studies were performed in order to gain additional insights into potential mechanism of action for PVT-1 including Reverse Phase Protein Array. Initial analysis suggest a role for PVT-1 in regulating the PI3K-AKT-TSC2 pathway. Conclusions: This suggests a potential oncogenic pathway in which PVT-1 enhances cancer stem cell phenotypes. On-going investigations are addressing potential PI3K/TSC2 pathway inhibitors, BEZ-2335 and LY3023414, which could be utilized to regulate PVT-1 mediated tumorigenic roles and cancer stem-like properties.
Peripheral cytokine as a pan-cancer predictor for immunotherapy with anti-PD-1/PD-L1 antibody.
Authors: Shoujian Ji, Huan Chen, Keyan Yang, Guanxiong Zhang, Henghui Zhang, Jianming Xu
Journal: Journal of Clinical Oncology (2020)

e15044 Background: Currently, only a small proportion of cancer patients may benefit from anti-PD-1/PD-L1 immune checkpoint inhibition (ICI), suggesting an urgent need for effective biomarkers. Due to the limited accessibility and heterogeneity of the tissue samples in advanced cancer, predictors as cytokines in the peripheral immune system revealed distinct advantages. Methods: Plasma samples were collected before anti-PD-L1/PD-L1 treatment in two subsets of patients, which comprises 21 esophageal squamous cell cancer (ESCC) patients in the discovery cohort and 61 pan-cancer cases in the validation cohort. A total of 59 immunological factors including cytokines, chemokines, and checkpoints were measured by using a Luminex immunoassay kit. Moreover, tumor infiltrating lymphocytes (TILs) were analyzed using multiplex immunohistochemistry (mIHC) in a subset of tissue samples from the combined cohort. Results: In the discovery cohort of ESCC patients, multiplex Luminex profiling data revealed that soluble PD-L1 and C-C motif chemokine 5 (CCL5/RANTES) were significantly upregulated in patients with clinic benefit at baseline. We therefore tested the predictive and prognostic value of the two peripheral factors, along with their combined signature, “the 2-cytokine signature”. In specific, the signature-high subgroups displayed remarkably increased disease control rate (DCR) and prolonged survival, versus that of the lower subgroups (p &lt; 0.05 for all comparison). More importantly, in the pan-cancer validation cohort, the three signatures exhibited a strong predictive value as well (PD-L1, AUC = 0.71; CCL5/RANTES, AUC = 0.71; the 2-cytokine signature, AUC = 0.72; p &lt; 0.05 for all comparison). Notably, the 2-cytokine signature revealed significant stratification power for overall survival (HR = 0.431, p &lt; 0.05) and progression free survival (HR = 0.423, p &lt; 0.01). Intriguingly, further quantitative analysis of the local tumor microenvironment by mIHC assays revealed a positive correlation between the levels of the 2-cytokine signature and NK cell infiltration. Conclusions: A combined peripheral signature comprising CCL5/RANTES and soluble PD-L1 appears to be an effective pan-cancer biomarker to identify patients who may benefit from anti-PD-1/PD-L1 monotherapy. Further analysis indicated a link between higher peripheral signature and enrichment of NK cells in the local microenvironment. Therefore, peripheral immunological features may play an essential role in guiding patient selection for ICI immunotherapy.
创伤后亚临床型脂肪栓塞综合征八例
Authors: 荆拓, 文军, 曲智杰, 王雅萍, 常洪
Journal: BMJ (2004)

沈阳市第七人民医院1993年6月～2001年12月发现8例创伤后亚临床型脂肪栓塞综合征(subclinical fat embolism syndrome,SFES)患者,报告如下。
First-in-human phase Ib study of ATRC-101, an engineered version of a patient-derived antibody targeting a tumor-restricted ribonucleoprotein complex.
Authors: Jonathan Eliot Benjamin, Nicholas Higgins, Carl Millward, Jeff Defalco, Amy Manning-Bog, Iraz T Aydin, Danhui Zhang, Shaun Lippow, Alexander Scholz, Yvonne Leung, Yanhong Zhu, Anna Sedello, Zane Rogers, Ish Dhawan, Daniel Emerling, William H. Robinson, Tito Serafini, Norman Greenberg
Journal: Journal of Clinical Oncology (2020)

TPS3168 Background: ATRC-101 is a fully human, engineered IgG1 version of an antibody discovered through a a target-agnostic screen to identify patient-derived antibodies that bind selectively to public tumor antigens. The parental antibody was identified from B cells in the active immune response of a patient receiving checkpoint therapy for Stage IV non-small cell lung cancer (NSCLC). A fluorescently conjugated version of ATRC-101 binds selectively to human tumor specimens including a majority of NSCLC, acral melanoma, breast, colorectal, and ovarian cancer samples. No reactivity of toxicological significance is found across a wide range of normal human tissues. ATRC-101 displays dose-dependent, single-agent activity in syngeneic mouse tumor models, including the EMT6 breast cancer model, which displays a T cell-excluded microenvironment often observed in human tumors, and in which checkpoint inhibitors targeting the PD-1 axis exhibit limited activity. Dosing with ATRC-101 in the EMT6 model causes marked changes in the tumor microenvironment, including a shift from the M2 to the M1 macrophage phenotype and infiltration of T cells. ATRC-101 does not appear to act via NK cell-driven ADCC; instead, activity in vivo is dependent both on Fc region interactions with Fc receptors, likely on myeloid rather than lymphoid cells, and on the presence of CD8+ T cells. ATRC-101 binds to a target that is a ribonucleoprotein (RNP) complex containing polyadenylate-binding protein 1 (PABP-1) bound to poly(A)RNA. Whereas both PABP-1 and poly(A)RNA are ubiquitously expressed at high levels in normal tissues and have been localized intracellularly, the ATRC-101 target is detected extracellularly on tumor cells grown in vivo. The basis for the tumor-selectivity of ATRC-101 as well as the extracellular localization of the target is under investigation. Ascending doses of ATRC-101 were well tolerated in multiple non-clinical safety studies. Methods: ATRC-101-A01 is an open-label, 3+3, Phase 1b safety study in patients with acral melanoma, NSCLC, breast, ovarian, and colorectal cancers. Participants are accruing in the first dose cohort. ATRC-101 is administered every 21 days up to 24 months or until disease progression. The primary objective of the trial is to determine the safety and tolerability of ATRC-101. Secondary objectives are to characterize the pharmacokinetic profiles of ATRC-101 and to assess antitumor activity as determined by RECIST 1.1 and lymphocytic infiltration in the tumor microenvironment. Clinical trial information: NCT04244552 .
Impact of high-risk features on disease-free survival (DFS) in patients (pts) with high-risk stage II colon cancer (CC) in ACHIEVE-2 trial as part of the IDEA collaboration.
Authors: Dai Manaka, Manabu Shiozawa, Masahito Kotaka, Makio Gamoh, Akio Shiomi, Akitaka Makiyama, Yoshinori Munemoto, Toshiki Rikiyama, Mutsumi Fukunaga, Takashi Ueki, Kohei Shitara, Hiroshi Shinkai, Nobuyuki Tanida, Eiji Oki, Kentaro Yamazaki, Eiji Sunami, Takeharu Yamanaka, Takayuki Yoshino, Atsushi Ohtsu, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2020)

4011 Background: The IDEA collaboration for high-risk stage 2 colorectal cancer patients (pts) demonstrated that for CAPOX, 3 months was non-inferior to 6 months treatment, while for FOLFOX, 6 months was superior to 3 months treatment. We investigated the impact of high risk features on disease-free survival (DFS). Methods: ACHIEVE-2, one of the 4 IDEA studies (SCOT, TOSCA, ACHIEVE-2, HORG), was an open-label, multicenter randomized trial for high-risk stage II colon cancer. High risk features are defined as one or more: T4, inadequate nodal harvest &lt; 12, poorly differentiated, clinical sign of obstruction and perforation or vascular invasion. The association of high risk features with DFS were measured by Cox regression analyses. Results: Between 2014 and 2017, ACHIEVE-2 enrolled 525 pts, out of whom 514 pts were the modified ITT (mITT) population; 432 received CAPOX (84.0%) and 82 did mFOLFOX6 (16.0%). High-risk features included 35.8% of T4, 12.8% of inadequate nodal harvest, 11.5% of poorly differentiated, 19.3% of obstruction, 6.4% of perforation and 87.5% of vascular invasion; 47.3% had one features, 35.2% had two, 14.6% had three, and 2.9% had four or more. With a median follow-up of 36.1 months, 3-year DFS rates were 88% in both arms, with a hazard ratio (HR) of 1.12 (95% CI, 0.67-1.87, p=0.67). In multivariate analysis, T4 (HR 3.77 [2.18-6.53], p&lt; 0.0001) and inadequate nodal harvest (HR 2.98 [1.59-5.59], p= 0.0006) remained independent significant negative prognostic factors. The 3-year DFS rates in T4 and Non-T4 diseases were 78% and 94% (p&lt;0.0001), while 3-year DFS rate in pts with inadequate and adequate nodal harvest were 77% and 90% (p=0.0059). No interaction was observed between treatment duration and T4 or inadequate nodal harvest. Conclusions: Our findings indicated the relative impact of high risk features on DFS varies across factors; T4 and inadequate nodal harvest &lt; 12 were more significant than the others. Our results must be interpreted within the combined analysis as well as within the reproducibility of results across the 4 trials. Clinical trial information: 000013036 .
窒息性胸廓发育不良二例报告并文献复习
Authors: 崔广梅, 孙清, 潘玉娟, 刘华林, 李晶
Journal: BMJ (2006)

窒息性胸廓发育不良(asphyxiating thoracic dysplasia,ATD)是一种少见的常染色体隐性遗传病.我院重症监护室(ICU)在1999年至2005年间共收治家族性病例2例,系同胞姊妹,报告如下。
Expansion of germline genetic testing criteria for prostate cancer yields findings across all stages of disease.
Authors: Sarah M. Nielsen, Russell Zelig Szmulewitz, Shan Yang, Rebecca Truty, Scott T. Michalski, Kingshuk Das, Nhu Ngo, Daniel Esteban Pineda Alvarez, Stephen E Lincoln, Robert Luke Nussbaum, Edward D. Esplin
Journal: Journal of Clinical Oncology (2020)

e17615 Background: Increasing evidence suggests criteria for germline testing of patients with prostate cancer (PCa) may miss potentially actionable pathogenic variants. A sponsored testing program with significantly broader criteria was initiated to increase access. Methods: We analyzed de-identified data from 2,252 men with PCa who received at least an 84 gene panel. Inclusion criteria were clinical stage ≥T2 and willingness of the patient and physician to participate. Positive results were categorized as: pathogenic (P), likely pathogenic (LP), or increased risk alleles (IRAs). Results: Clinical stage was available in 1825 men (81%): 541 (30%) were stage II, 228 (12%) stage III, and 1,056 (58%) stage IV (Demographics Table). Among all men, 297 (13%) had positive results, including 286 P/LP variants in 38 genes and 31 IRAs in APC and HOXB13. There was no statistically significant association between stage and positive rate. Of men with positive variants, only 30% reported a family history of prostate, breast, ovarian or pancreatic cancer. The most common positive variants were in BRCA1 (9) , BRCA2 (43) , PALB2 (11) , ATM (36) , CHEK2 (58) , HOXB13 (20) , and mismatch repair genes (8). With respect to ethnicity, the highest positive rate was observed in Ashkenazi Jews (23.8%) and the lowest in African Americans (5.4%). Overall, 190 (70%) of men had P/LP variants conferring eligibility for gene-specific precision therapies or clinical trials based on variants in homologous repair (182), or mismatch repair (8) genes. Conclusions: In a broad PCa patient population, we found overall germline positive rate of 13%, with no statistical difference in this rate with respect to stage. Overall, these data suggest that broader testing criteria and more access to testing could lead to better informed care for many additional patients and their families. [Table: see text]
Platelet-rich plasma trigger point injection treatment for chronic achilles insertion tendonitis
Authors: Guo-you Zou, Wei-tao Jia, Min-qian Zheng, Xiao-zu Xu, Zheng-chun Cao, Jun Yin
Journal: BMJ (2013)

Retrospective analysis was performed for the clinical data of 15 chronic insertion achilles tendinitis patients undergoing platelet-rich plasma (PRP) trigger point injection. The scores of Validated Victorian Institute of Sports Assessment-Achilles (VAS-A) and foot function index (FFI) improved greatly versus pre-treatment (all P<0.05). Tendon insertion structure inflammation decreased significantly on magnetic resonance imaging. At the last follow-up, all patients recovered normal gait and daily activity. The trigger point injection of PRP is efficacious for chronic insertion achilles tendinopathy.


Key words: 
Tendinopathy, achilles tendon; Platelet-rich plasma
Safety of ropinirole in the treatment of Parkinson's disease
Authors: Shuhua Li, Wen Su, Haibo Chen, Xiangyu Zeng
Journal: BMJ (2014)

To explore the safety of ropinirole in the treatment of Parkinson's disease(PD). A total of 221 PD patients participated in a multi-center, 12-week randomized, bromocriptine-controlled, double-blind, double-dummy and parallel-group trial.The safety was assessed on the basis of adverse reactions, blood pressure, pulse, laboratory parameters and electrocardiography recordings.The incidence of adverse reaction was 34.9% in ropinirole group and 34.8% in bromocriptine group.And the frequency of adverse reactions had no inter-group statistical significance(χ2=0.000, P=0.995). Ropinirole has an excellent profile of safety in the treatment of Chinese PD patients.


Key words: 
Parkinson's disease; Bromocriptine; Ropinirole