tbuckley/cabot-search huggingface dataset:
Safety and efficacy results of GC027: The first-in-human, universal CAR-T cell therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL).
Authors: Xinxin Wang, Shiqi Li, Lei Gao, Zhongtao Yuan, Kun Wu, Lin Liu, Le Luo, Yao Liu, Cheng Zhang, Jia Liu, Chunhui Yang, Yu Li, Jiaping He, Xun Ye, Zhimin Li, Xu Tan, Jianning Ge, Wei Cao, Sanbin Wang, Xi Zhang
Journal: Journal of Clinical Oncology (2020)

3013 Background: Patients with r/r T-ALL usually have high relapse and mortality rates. Due to shared common surface antigen and potential contamination by malignant cells, development of autologous CAR-T therapies for r/r T-ALL has been lagged, regardless of the costly and lengthy process of autologous CAR-T production. Through targeting CD7, a common T cell antigen highly expressed in &gt;95% T-ALL samples, universal CAR-T product GC027 has been developed using lentivirus and CRISPR/Cas9 system with demonstrated anti-leukemia ability in a murine xenograft model. Methods: Preliminary safety, anti-leukemic activity and expansion kinetics of GC027 are being evaluated in a single-arm, open-label, multi-center, prospective study for treating adult patients with r/r T-ALL. To date, a total of 5 patients (age 19-38 yrs, median 24 yrs) were enrolled with marrow tumor load 4-80.2% (median prior lines 5). All 5 pts have received a 6-day enhanced preconditioning chemotherapy followed by a single infusion of GC027. No patient was bridged to HSCT. Adverse events, disease response, and expansion kinetics were evaluated in this study. Results: As of Feb. 6, 2020, 5 pts had received a single dose of GC027, including 1 at 0.6x10 7 /kg, 3 at 1x10 7 /kg, 1 at 1.5x10 7 /kg. 3 pts achieved MRD negative complete responses (MRD- CR) at D28 evaluation and remained MRD- at follow-up re-evaluations (161, D118, 61, respectively) without bridging to HSCT. 1 pt just achieved D28 MRD- CR at time of submission. 1 pt achieved MRD+ CR at D14, but his disease progressed at D29 and deceased due to relapse. In all 4 pts with MRD- CR, peak expansions of GC027 in peripheral blood were observed between week 1-2, analyzed by flow cytometry and Q-PCR. Grade 3 cytokine release syndrome (CRS) occurred in 4 pts and Grade 4 CRS occurred in 1 pt (ASBMT Consensus Grading). CRS symptoms were manageable and resolved after treatment and supportive care. None developed neurotoxicity or GvHD. One had prolonged cytopenia due to fungal infection and required anti-fungal therapy. Conclusions: With a single infusion of GC027, 80% of the patients had robust CAR-T cell expansion and achieved persistent MRD- CR without using any biologics as part of the preconditioning therapy or bridging to HSCT. The first-in-human, universal CAR-T therapy for r/r T-ALL, GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile. The trial enrollment is ongoing and updated data will be presented at the meeting. Clinical trial information: ChiCTR1900025311 .
Survival outcomes of sarcomatoid renal cell cancer (sRCC) compared to clear cell renal cell cancer (ccRCC): An analysis of SEER data.
Authors: Ruby Gupta, Filip Ionescu, Vishal Jindal, John Khoury, Nwabundo Ifeyinwa Anusim, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2020)

e17101 Background: Renal cell carcinoma (RCC) with sarcomatoid differentiation is a highly aggressive form of RCC. The presence of even a small component of sRCC was shown to independently predict poor survival compared to RCC without sarcomatoid features. We studied the epidemiology and survival outcome of sRCC compared to ccRCC by reviewing the SEER data. Methods: Patients (pts) with histologically confirmed sRCC and ccRCC between 2012-2015 were reviewed in SEER database. Variables included age, gender, ethnicity, histologic grade, stage at diagnosis, and nephrectomy. Primary outcome was 5 year Disease Specific Survival (DSS). Data was analyzed using Kaplan Meier curves and Cox proportional hazards model. Results: A total of 31, 293 pts with RCC were identified in SEER database between 2012 to 2015. 611 pts had sRCC while 30, 682 had ccRCC. The two groups had almost similar demographic features, including mean age (63 ±12 for sRCC vs 61±12 years for ccRCC), male: female ratio (vs 2.3:1 vs 1.7:1) and Caucasian ethnicity (82% vs 85%). More than half of sRCC patients (62%) were metastatic at diagnosis compared to only 11% of ccRCC, which presented most commonly as stage I disease (63%). The histologic grade was higher in sRCC patients (43% grade 4 vs 45% grade 2 in ccRCC subjects). Nephrectomy rates were almost similar for stages I-III in the two groups (94% in sRCC vs 93% in ccRCC) while lower in stage IV sRCC (44% vs 54%). Across all stages and at every time point, sRCC was associated with increased mortality in the univariate analysis. In the multivariate regression analysis (table), advanced stage was the strongest independent predictor of mortality (HR 11.9), followed by high histologic grade (HR 3.6) and sarcomatoid histology (HR 2.9). Nephrectomy was protective (HR 0.3). Age was associated with worse outcomes (HR 1.016 per unit change). Conclusions: sRCC are more aggressive and tend to present as metastatic disease. sRCC has worse outcomes across all stages compared to ccRCC even after adjusting for potential confounders. Advanced stage and histologic grade remain the two strongest predictors of disease-specific mortality, sarcomatoid histology demonstrated a significant impact on outcome. [Table: see text]
Survey on the application of Chinese Hypertension Prevention and Treatment Guideline by general practitioners in Shanghai
Authors: Xiangjie Zhang, Tianhao Wang, Jie Gu, Yuan Zhang
Journal: BMJ (2014)

To investigate the status of application of Chinese Hypertension Prevention and Treatment Guideline (Guideline) by general practitioners (GPs) in Shanghai.A questionnaire survey was conducted among 260 GPs from 8 communities in Xuhui District of Shanghai during March 2011 to December 2012.Among all participants, 94.2% knew the Guideline.The overall correct rate was 56.2%; that of epidemiology, diagnosis, treatment, two-way referral and community management of hypertension was 49.2%, 54.5%, 60.6%, 56.9% and 32.3%, respectively.There were significant differences in correct rates of the questionnaire between GPs with different age, gender, education and community (P=0.000, 0.035, 0.000, 0.000). The correct rates of epidemiology and treatment in GP teaching bases (58.5% and 62.6%) were higher than those in non-teaching bases (39.2% and 58.4%) (P=0.002, 0.040). But there was no difference in overall correct rate between these two groups (P=0.095). The results indicate that the understanding and application of Hypertension Guideline by General practitioners in community is insufficient.Teaching hospitals should carry out systematic, comprehensive, sustained, targeted training course in order to improve the diagnosis and treatment levels of hypertension for general practitioners in community.


Key words: 
Hypertension; Questionnaires; General practitioners
酒后头外伤致无动性缄默症一例
Authors: 崔金国, 曹金华
Journal: BMJ (2007)

患者男,26岁,因言语及四肢活动障碍1 h于2005年11月15日晚21:00入院.患者于当日酒后呕吐与人吵架时不慎摔倒,枕部受伤,随即出现意识模糊,言语不能,四肢活动障碍,小便失禁。
A phase Ib study of TQ-B2450 plus anlotinib in patients with advanced solid tumor.
Authors: Ying Cheng, Hongxia Cui, Chunjiao Wu, Yanping Wang, Tingting Zhang, Ying Xin, Jinhua Xu, Yan Chen, Zili Li, Ying Wang, Huafang Wei, Jing Zhu, Tianying Du
Journal: Journal of Clinical Oncology (2020)

3065 Background: Anlotinib, an antiangiogenic multi-target tyrosine kinase inhibitor, significantly improved clinical outcomes in solid tumors. TQ-B2450 is an engineered anti-programmed death-ligand 1 antibody. This onging phase 1b study aimed to assess the safety and effect of TQ-B2450 plus anlotinib in advanced solid tumors. Methods: This phase 1b study, which included a dose-escalating phase and an expansion phase, enrolled patients with advanced solid tumor who failed in or had no standard treatment between June 2019 and January 2020.Eligible patients were firstly assigned into sequential dose-escalating cohorts including 10mg and 12mg anlotinib plus TQ-B2450 following the conventional 3+3 design. If the starting dose of 10mg anlotinib led to ≥2 dose-limiting toxicities (DLTs), 8mg anlotinib would be administered. After the dose-escalating phase, eligible patients were enrolled into the expansion cohort. The primary outcomes were safety and objective response rate. Results: In the dose-escalating phase, three eligible patients received 10mg anlotinib plus TQ-B2450 had no DLTs in the first cycle, neither did three patients with 12mg anlotinib plus TQ-B2450. Then the expansion phase started, sixteen patients received 12mg anlotinib plus TQ-B2450. Finally, a total of 22 patients were included ( 6 small cell lung cancers [SCLC], 8 non-small cell lung cancers [NSCLC], 2 colorectal cancers, 2 breast cancers, 2 ovarian cancers, 1 thymic carcinoma and 1 cervical cancer). Ten ≥3 grade adverse events were observed (Table). Seventeen patients underwent at least once effect evaluation. One SCLC patient with 10mg anlotinib plus TQ-B2450 had confirmed partial responses (PR). Four patients with 12mg anlotinib plus TQ-B2450 had unconfirmed PR (2 SCLC and 2 NSCLC). And 9 patients had stable disease, 3 patients had progression disease. Conclusions: 12mg anlotinib plus TQ-B2450 showed an acceptable safety profile and promising response in advanced solid tumors. Clinical trial information: NCT03897283. [Table: see text]
抗甲状腺药物的不良反应
Authors: 赖亚新, 单忠艳
Journal: BMJ (2008)

抗甲状腺药物(antithyroid drug,ATD)应用的历史已经超过了半个世纪,目前仍然是治疗甲状腺功能亢进症(甲亢)的主要方法之一.在我国,常用的ATD包括甲巯咪唑(methylimidazole thiamazole,MMI)和丙硫氧嘧啶(propylthiouracil,PTU)。
谈急诊科急危重症的识别及判定
Authors: 李春盛
Journal: BMJ (2008)

在急诊的临床实践中,使急诊科医生最感困难的是如何在众多急诊患者中识别潜在危及生命的因素,以减少漏诊和误诊,避免医疗纠纷的发生.医院管理者也一直在探讨用什么方法或客观指标来制定规范或标准,以判定哪些患者真正需要急救,哪些不是急救患者却入住急诊抢救室,以使有限的医疗急救资源用于最需要的危重患者,不至于造成浪费。
Clinical analyses of 11 cases with pituitary stalk interruption syndrome
Authors: Yinghui Zhang, Bing Wang, Zhizhen Li, Xiaojun Ma, Dabei Fan
Journal: BMJ (2015)

Eleven male patients with pituitary stalk interruption syndrome (PSIS) at our hospital were retrospectively analyzed with respects to clinical features, endocrine status and imaging characteristics.The clinical manifestations included growth retardation and delayed puberty. All of them were deficient in growth hormone and pituitary gonadotropin secretion. Secondary hypothyroidism and hypocortisolism occurred in 8 patients and one had concurrent central diabetes insipidus. MRI with gadolinium contrast revealed no pituitary stalk or slim and anterior pituitary hypoplasia with ectopic posterior pituitary. The clinical characteristics of PSIS are growth retardation and delayed puberty, partial or complete adenohypophyseal dysfunction. The detection of hypothalamic pituitary region by MRI is an important diagnostic tool.


Key words: 
Pituitary diseases; Pituitary stalk interruption syndrome
Safety and clinical evaluation of dual inhibition with pertuzumab and trastuzumab in HER-2-positive breast cancer patients.
Authors: Christoph Suppan, Daniel Steiner, Valentina Eva Klocker, Florian Posch, Elisabeth Christina Henzinger, Herbert Stoeger, Nadia Dandachi, Marija Balic
Journal: Journal of Clinical Oncology (2020)

e12520 Background: The addition of Herceptin to standard chemotherapy improved survival in patients with Her-2-positive breast cancer in neoadjuvant, adjuvant and metastatic setting. In higher tumor stage, the addition of pertuzumab is now standard of care and associated with a favorable toxicity profile. The purpose of this study was to evaluate the safety and efficacy of the biosimilar trastuzumab-dttb in combination with pertuzumab in Her-2-positive breast cancer patients. Methods: Thirty-five female patients with Her-2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz between September 2018 and August 2019 were included. Summary measures are reported as medians 25 th – 75 th percentile for continuous variables and as absolute frequencies (%) for count data. Results: Thirty-five patients received a median of four [3-7] cycles of trastuzumab-dttb plus pertuzumab. The median cumulative trastuzumab-dttb dose was 1904mg [1560-2640] and the median cumulative pertuzumab dose was 2100mg [1680-3360]. All patients had a normal baseline LVEF (&gt; 50%) prior to the initiation of trastuzumab-dttb plus pertuzumab treatment with a median LVEF of 60% [60-65]. At completion of trastuzumab-dttb plus pertuzumab treatment (or in case of ongoing therapy the last EF assessment), the median LVEF was 60.0 % [58-62]. 21 patients had a median absolute LVEF decline of 1% -5-0], corresponding to a median percent change of 1.7 percent points [-7.7-0]. Two patients (5.7%) had a LVEF reduction ≤50%. None of the patients had a decline in LVEF of ≥ 10 %. In 8 patients, a switch from Herceptin to trastuzumab-dttb was tolerated well and these were also included in the analyses. In only two palliative patients, pertuzumab was either interrupted or stopped due to diarrhea and appetite loss, while trastuzumab-dttb was ongoing. 24 of 35 patients (69%) were treated with trastuzumab-dttb plus pertuzumab in the neoadjuvant setting. Two of these patients were treated for local relapse and were excluded for efficacy assessment. Of the remaining 22 patients, 11 patients achieved a pCR (ypT0/ypTis and ypN0). Conclusions: In these series of Her-2-positive breast cancer patients, the combination of trastuzumab-dttb/pertuzumab was consistent with the known safety and efficacy profile of Herceptin/pertuzumab.
Survey on employment intention of medical students in six Chinese universities
Authors: Zhigang Pan, Junling Gao, Lijun Sun, Yongming Ding
Journal: BMJ (2014)

Objective
To survey the employment intention of medical students in different universities in China.


Methods
A total of 1354 fourth-year or above medical students from 6 medical universities in China were selected for survey by random cluster sampling. A self-designed questionnaire was used to investigate the basic information of students and their employment intention.


Results
Overall 46.5% (620/1333) of all students choose cities in economically-developed region as their desired working sites. 45.5% (363/797) of students studying in 4 Shanghai medical universities and 34.5% (185/536) in other 2 non-Shanghai universities would first choose their original cities as working sites, respectively. 81.3% (1078/1326) of students preferred working in large public hospital, especially for those studying for higher degrees (88.0%, 581/660). 51% of undergraduates expected 4000 RMB as monthly pay for graduation. Male students (54.6%, 332/608) expected more income than female (47.9%, 335/700), graduates (57.9%, 377/651) expected higher payment than undergraduates (44.1%, 290/657).


Conclusion
The survey shows that medical students in China mainly prefer cities and large public hospitals as working sites for their career development.


Key words: 
Employment; Medical students; Questionnaires
Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford progeria syndrome
Authors: Florian Köhler, Felix Bormann, Günter Raddatz, Julian Gutekunst, Samuel Corless, Tanja Musch, Anke S. Lonsdorf, Sylvia Erhardt, Frank Lyko, Manuel Rodríguez-Paredes
Journal: Genome Medicine (2020)

Abstract Background Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid disease characterized by the early onset of age-related phenotypes including arthritis, loss of body fat and hair, and atherosclerosis. Cells from affected individuals express a mutant version of the nuclear envelope protein lamin A (termed progerin) and have previously been shown to exhibit prominent histone modification changes. Methods Here, we analyze the possibility that epigenetic deregulation of lamina-associated domains (LADs) is involved in the molecular pathology of HGPS. To do so, we studied chromatin accessibility (Assay for Transposase-accessible Chromatin (ATAC)-see/-seq), DNA methylation profiles (Infinium MethylationEPIC BeadChips), and transcriptomes (RNA-seq) of nine primary HGPS fibroblast cell lines and six additional controls, two parental and four age-matched healthy fibroblast cell lines. Results Our ATAC-see/-seq data demonstrate that primary dermal fibroblasts from HGPS patients exhibit chromatin accessibility changes that are enriched in LADs. Infinium MethylationEPIC BeadChip profiling further reveals that DNA methylation alterations observed in HGPS fibroblasts are similarly enriched in LADs and different from those occurring during healthy aging and Werner syndrome (WS), another premature aging disease. Moreover, HGPS patients can be stratified into two different subgroups according to their DNA methylation profiles. Finally, we show that the epigenetic deregulation of LADs is associated with HGPS-specific gene expression changes. Conclusions Taken together, our results strongly implicate epigenetic deregulation of LADs as an important and previously unrecognized feature of HGPS, which contributes to disease-specific gene expression. Therefore, they not only add a new layer to the study of epigenetic changes in the progeroid syndrome, but also advance our understanding of the disease’s pathology at the cellular level.
休克与消化道出血
Authors: 陈绍潞
Journal: BMJ (2009)

患儿男,11岁,早上起床后感觉头晕、无力,即来门诊.无发热,神志清,面色苍白,脉搏120 次/min,细弱,血压70/40 mm Hg(9.3/5.3 kPa),血糖正常.由于患儿无感染性疾病病史及临床表现,不符合感染性休克,接诊医生考虑有心肌炎、心源性休克可能,遂做心电图检查,结果除窦性心动过速外,无其他异常.查血常规也正常.立即予静脉输注等渗电解质溶液,同时请我会诊。
Body composition and treatment-related toxicity in pediatric lymphoma.
Authors: Aman Wadhwa, Kandice Barnett, Chen Dai, Joshua Richman, Andrew Michael McDonald, Grant R. Williams, Smita Bhatia
Journal: Journal of Clinical Oncology (2020)

e22503 Background: Body composition is an emerging predictor of toxicity and survival in older adults with cancer ( Shachar, Eur J Can, 2016); however, its role in pediatric cancer is not known. We examined body composition (using computed-tomography [CT] scans at the 3 rd lumbar level) in children with lymphoma (Hodgkin [HL] and non-Hodgkin [NHL]) at cancer diagnosis and examined its association with treatment-related toxicities. Methods: We constructed a retrospective cohort of 87 consecutive children (HL: n = 45; NHL: n = 42) diagnosed between 2000 and 2015 (2-21y at diagnosis) with pretreatment abdominal CT scans. Body composition was assessed using sliceOmatic (TomoVision) and included skeletal muscle index (SMI, cm 2/ m 2 ), skeletal muscle density (SMD: Hounsfield units [HU]), and height-adjusted total adipose tissue (hTAT: sum of visceral, intramuscular and subcutaneous adipose tissue, cm 2/ m 2 ). For the analysis, we used skeletal muscle gauge (SMG = SMI x SMD, expressed per 1000 in arbitrary units [AU]) and hTAT. Sociodemographics, disease and treatment details, as well as toxicities (CTCAE v5) were abstracted from medical records. Proportion of chemotherapy cycles with grade 4 hematologic or grade 3-4 non-hematologic toxicities were calculated (percent toxicity). Generalized linear regression models were constructed to examine associations between body composition metrics and toxicities, adjusting for age at diagnosis, gender, race/ethnicity and lymphoma subtype. Results: Median age at diagnosis was 12.9y (range, 2-18.5y); 60.9% males; 60.4% non-Hispanic white. Median BMI%ile was 62 (0-99), median SMG was 2.2AU (0.9-3.7) and median hTAT was 20.1 cm 2/ m 2 (0.04-226.7). Overall, the mean percent toxicity for grade 4 hematologic and grade 3-4 non-hematologic toxicity was 38.9% (±32.6) and 31.4% (±32.6) respectively. Correlation was poor between SMG and BMI%ile ( R 2 = 0.04), SMG and hTAT ( R 2 = -0.01) and moderate between hTAT and BMI%ile ( R 2 = 0.4). SMG was significantly associated with grade 4 hematologic percent toxicity ( β= -18, P= 0.007) after adjusting for hTAT and cancer type. BMI%ile was not associated with grade 4 hematologic percent toxicity ( β= -0.09, P= 0.5). Non-hematologic percent toxicity was not associated with BMI%ile, hTAT or SMG. Conclusions: In this first study of its kind, we find that children with poorer muscle quality are more likely to experience grade 4 hematologic toxicities. These findings form the basis for larger studies to incorporate body composition when developing prediction models for chemotherapy-related toxicity and disease outcomes.
Deep learning-based unsupervised morphological subtyping in histopathology images of gastric cancer.
Authors: Kyu-Hwan Jung, Jeonghyuk Park, Kyungdoc Kim, Yeong Won Kim, Hyunho Park, Myeong-Cherl Kook, Dong-Il Kim
Journal: Journal of Clinical Oncology (2020)

e16580 Background: Gastric cancer subtyping system such as Lauren classification is widely used in clinical practice since it is an independent prognostic factor, and also provides the basis for individualized treatment. However, Lauren classification showed low reproducibility because it is based on qualitative method. Thus, a more reproducible system has been required. In this study, we explore the concordance between a cancer detection model (CDM)-based unsupervised subtyping and a current classification system. Methods: We focused on Lauren classification since it has relatively simple major subtypes: intestinal and diffuse types. 88 resection cases of gastric cancer are collected. Two experienced gastrointestinal pathologists evaluated each case independently by Lauren’s criteria. 200 cancer region image patches per case and its features extracted by the CDM were clustered into five groups via k-means clustering. We then defined the ratio of the number of patches in each cluster group as the case-level feature. Cases are clustered into two groups via k-means clustering using the features. We named this case-level clustering result as a deep learning-based subtyping (DLS), hereafter. Results: DLS showed a high correlation with Lauren classification: intestinal and diffuse subtype. The kappa scores between the pathologists and algorithm (0.765 and 0.796) were higher than between pathologists (0.700). The cluster centers corresponding to intestinal and diffuse types were [44.6, 21.5, 47.5, 63.7, 22.7] and [35.5, 148.2, 4.0, 9.0, 2.3], respectively. Further review of the patches contributing to the second feature (21.5 and 148.2) confirmed that they demonstrate typical morphological characteristics of diffuse type. Conclusions: Our analysis showed that the morphological characteristics of Lauren classification were inherent in gastric cancer detection task and WSIs can be subtyped by the data-driven, and unsupervised manner. Furthermore, DLS was more reliable than human from the concordance results. This suggests that the DLS can supplement current classification systems or be a new subtyping system. [Table: see text]