tbuckley/cabot-search huggingface dataset:
Survival from time of transformation in patients with transformed lymphoma at time of diagnosis.
Authors: Alaina Kelly, Kirsten M Boughan, Patricio Rojas, Nausheen Ahmad, Akiva Diamond, Marcos J.G. De Lima, Paolo Fabrizio Caimi
Journal: Journal of Clinical Oncology (2020)

e20054 Background: Histologic transformation (HT) to aggressive lymphoma can occur in indolent lymphoma and is considered to convey poor prognosis. Most data come from follicular lymphoma (FL). We conducted a retrospective analysis to compare outcomes of transformed marginal zone lymphoma and lymphoplasmacytic lymphoma (tMZL/LPL) with those of transformed FL (tFL). Methods: We collected data from patients diagnosed with HT between 2000 and 2018. Transformed CLL was excluded. Survival estimates were done with the Kaplan Meier method; comparisons were done with log-rank test. The effect of covariates on OS was evaluated with Cox proportional hazards method. Results: We identified 87 pts (58 tFL, 29 tMZL/LPL). There were no differences in baseline characteristics, except for COO subtype by Hans criteria and circulating IgM. There were no differences in OS or EFS based on the underlying lymphoma subtype (OS: tFL = 60.1m vs. tMZL/LPL = 64.8m, p = 0.53; EFS: tFL = 25.2m vs. tMZL/LPL = 27.6m). Univariate and multivariate analyses identified age at HT (HR for age &gt; 60 = 3.5, 95% CI: 1.7-7.6), poor performance status (HR for ECOG ≥3 = 23, 95% CI: 7.3-70) and having a previous diagnosis of indolent lymphoma (HR for previous diagnosis = 3.7, 95% CI: 1.87-7.4) as adverse risk factors for OS after HT. Pts with previous diagnosis of indolent lymphoma with subsequent HT had inferior OS than pts presenting first with HT (median OS 25m vs. not reached, p &lt; 0.0001); EFS (median EFS for treated pts = 11m vs. 49m). Conclusions: Underlying lymphoma does not affect OS after HT and long term survival can be achieved in pts who receive treatment. tMZL/LPL is more frequently of non-GCB origin has monoclonal IgM. Pts who present with HT as their first lymphoma-related event have better OS. These findings will lead to further exploration of the genetic changes that occur at the time of transformation of indolent lymphomas. [Table: see text]
速效胰岛素类似物的临床应用
Authors: 傅汉菁
Journal: BMJ (2012)

今年是胰岛素问世90周年.90年来,从动物胰岛素纯化到单峰胰岛素、单组分胰岛素,再到人胰岛素,每一次新型胰岛素制剂的研制成功都是胰岛素发展史上的一个飞跃,给临床提供了更符合降糖需要的新胰岛素.理想的胰岛素治疗应该使糖尿病患者的血胰岛素水平接近生理性胰岛素分泌模式,而目前在临床广泛应用的人胰岛素仍不能完全满足临床需要,因而,胰岛素的研制又从人胰岛素进展到胰岛素类似物.这是胰岛素历史上的又一个重大飞跃,使胰岛素的临床应用进入了胰岛素类似物的新时代。
Cardiotoxicity and heart failure in patients receiving chemotherapy: A nationwide analysis.
Authors: Arya Mariam Roy, Akshay Goel, Manojna Konda, Rashmi Verma
Journal: Journal of Clinical Oncology (2020)

e19097 Background: Cardiotoxicity resulting in heart failure (HF) is one of the most common complications of chemotherapy which significantly impacts patient care and results in poor clinical outcomes. Based on prior clinical studies, cancer patients have multiple cardiovascular comorbidities and higher prevalence of cardiovascular diseases which makes them more vulnerable to cardiovascular injuries during chemotherapy. It may increase their risk of developing cardiomyopathy or worsening of the already existing cardiac conditions which result in HF and death. Methods: We conducted a retrospective analysis of the National Inpatient Sample Database for the year 2017. Patients who were admitted in the hospital for chemotherapy administration and those who have HF were identified using ICD-10 codes. The mortality of patients with HF who receive chemotherapy and the factors affecting the mortality were studied. The two groups that were studied are chemotherapy patients with and without HF. Results: A total of 29,018 admissions for chemotherapy were identified during the year 2017. Out of these, 2.64% of patients were found to have HF (n = 767). The median age for the patients who have an associated diagnosis of HF was 63. The overall mortality of chemotherapy-related admission was 0.80%. The mortality of patients with HF who received chemotherapy was higher than the patients without HF who received chemotherapy (4.3% vs 0.7%, OR = 1.82, p = 0.001). Patients with HF who were admitted for chemotherapy were 82% more likely to die while in hospital than those without HF. Females who have HF had a higher mortality rate and had 64% more odds of dying while admitted for chemotherapy than males with HF (7.92% vs 1.93%, OR = 1.64, P = 0.00, CI = 1.31- 1.82). Also, interestingly Asians who have HF had higher mortality while admitted for chemotherapy than all the other races who had HF who received chemotherapy (Asians vs Caucasians vs African Americans 13.63% vs 4.64% vs 2.85%, p = 0.041). Conclusions: The mortality of patients with heart failure who receives chemotherapy is higher than the overall mortality from chemotherapy-related side effects. Females and Asians who have HF had higher mortality while admitted for chemotherapy. Patients who have prior cardiovascular diseases have to be given diligent care and special attention while we plan for chemotherapy to prevent the development or worsening of heart failure.
The predictive potential of the spatial signature of lymphocytes in breast cancer patients.
Authors: Nora Balint-Lahat, Chen Mayer, Noa Ben-Baruch, Ady Yosepovich, Kira Sacks, Shahar Ish-Shalom, Yossef Molchanov, Maya Dadiani, Dana Morzaev-Sulzbach, Einav Nili Gal-Yam, Albert Achtenberg, Yuval Gabay, Roman Gluskin, Alon Griosman, Yuval Shachaf, Amir Luchtenstein, Ori Zelichov, Kathrina Alexander, Alexander J. Lazar, Iris Barshack
Journal: Journal of Clinical Oncology (2020)

530 Background: Tumor-infiltrating lymphocytes in breast cancer have emerged as both a prognostic and a potentially predictive immunotherapy biomarker. Advancements in artificial intelligence can extract pathology-based spatial immune fingerprints for use as treatment decision support tools. Methods: We examined 908 primary breast cancer patients with whole slide images (WSI) available from TCGA database. Digital structuring of WSIs included automated detection of lymphocytes, tumor and tumor adjacent stroma, using deep learning-based semantic segmentation. Prognosis was defined as progression free interval (PFI). A Cox Survival analysis was used to detect prognostic spatial features. We used principal component analysis (PCA) to reduce and decorrelate significant features. The resulting PCA features were used to fit the final model. The model was then validated on an independent database of WSI of breast lumpectomies, from two tertiary hospitals in Israel. Results: The analysis included 908 WSI. The average age was 58.4 years old, with a majority of early stage breast cancer (76.7%, stage I and II). The detection performance for tumor area and lymphocytes reached F1 scores of 99% and 97% respectively, in comparison to human annotation. In the Kaplan Meier (KM) analysis of 414 early stage luminal breast cancers, a high number of lymphocyte clusters (LC) and a high ratio between stromal lymphocyte density and tumor lymphocyte density (LD-S/LD-T) were significantly associated with longer PFI (p = 0.005 and p = 0.038, respectively). Based on these features, two continuous PCA features were added to the multivariate model, and remained significantly associated with PFI after adjusting for age (HR = 1.19, 95% CI 1.05-1.35; HR = 1.26 95% CI 1.03-1.55). The validation set was underpowered (n = 79) and data is still being collected. In a preliminary KM analysis of 37 early stage luminal breast cancer cases from the validation set, LD-S/LD-T was significantly associated with longer PFI (p = 0.046). Conclusions: In our study, LC and LD-S/LD-T, presumably surrogate measures of peritumoral lymphocytes, were found significantly associated with longer PFI.
经颈低领切口行胸腺切除治疗重症肌无力
Authors: 束余声, 孙超, 陆世春
Journal: BMJ (2009)

相关临床资料不断证明,外科手术在治疗重症肌无力方面有一定价值,但对胸腺切除术的手术指征及采取的手术径路仍然未取得共识.本研究对15例重症肌无力合并胸腺增生或胸腺瘤行经颈切口胸腺切除术患者的临床资料进行分析,探讨经颈低领切口行胸腺切除治疗重症肌无力的可行性和疗效。
Expression of CD47 and CALR in myeloproliferative neoplasms and myelodysplastic syndrome: Potential new therapeutical targets.
Authors: Ciro Roberto Rinaldi, Kristian Boasman, Matthew Simmonds
Journal: Journal of Clinical Oncology (2020)

7557 Background: Myelodysplastic neoplasms (MPN) and myelodysplastic syndrome (MDS) are myeloid malignancies tendency to evolve into acute myeloid leukaemia. We investigate the expression and cellular localisation of pro-phagocytic CALR and anti-phagocytic CD47 in untreated and treated patients with essential thrombocythemia (ET), polycythemia vera (PV) myelofibrosis (MF), and in MDS patients in comparison with healthy controls. Methods: Mononuclear cells were collected by Ficoll separation, from peripheral blood of 27 MPN (8 PV, 16 ET, 3 MF); 14 MPN patients received cyto-reductive therapies (Hydroxyurea, Anagrelide or Ruxolitinib); 10 MDS patients and 4 controls. Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: CD47 showed higher expression of its overall protein on MPN cell membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR expression in all MPN subtypes when patients were treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 cell membrane expression after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%). In MDS cells CD47 is overexpressed compared with controls (CD47- 11.31 vs 2.2 fold, respectively) and it mainly located to the membrane. Interestingly the degree of CD47 expression correlated to patients IPSS-R, increasing from low risk to high risk (low – 15.7%, intermediate 1 – 41.3%, intermediate 2 – 53.9% and high – 67.6%). CALR expression is also reduced in MDS cells comparing with controls when split by IPSS-R risk score (low – 9%, intermediate 1 – 11.9%, intermediate 2 – 17%, high – 17.9% Vs control - 29.1%). Conclusions: CD47, but not CALR, is overexpressed on the membrane of patients with MPN and MDS. In MDS, we observed a progressive increase in CD47 expression as the MDS evolve in accordance to the IPSS-R risk score. In MPN patients we observed a significant difference in CD47 expression across different MPN subtypes. The use of anti-CD47 antibodies could represent a new strategy to enhance the pro-phagocytic signal via increasing the CALR expression, and in combination with standard cyto-reduction therapy, might represent a new therapeutical strategy in both MPN and MDS.
安全标记胃镜活检钳的临床应用
Authors: 孙产智
Journal: BMJ (2009)

自2005年1月至2007年12月采用自制的安全标记胃镜活检钳(已获国家专利,专利号ZL97245466.7)对100例受检者进行了胃镜下采取活组织标本检查(活检)489次(块),取得良好效果。
消翳散治疗单纯疱疹病毒性角膜炎疗效观察
Authors: 孙秋香, 马路生, 东长霞, 李元彬, 代秀玉
Journal: BMJ (2008)

单纯疱疹病毒性角膜炎(herpes simple keratitis,HSK)是眼科常见多发病,病程长,反复发作,可严重危害患者视力,其致盲性居角膜病首位[1].多年来,我们采用自治中药消翳散结合西药治疗81例单纯疱疹病毒性角膜炎患者,与80例单纯西药治疗相比,其疗效显著.报告如下。
Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM.
Authors: Salah-Eddin Al-Batran, Ralf Dieter Hofheinz, Harald Schmalenberg, Dirk Strumberg, Eray Goekkurt, Stefan Angermeier, Thomas Zander, Jochem Potenberg, Hans Georg Kopp, Daniel Pink, Gabriele Margareta Siegler, Michael Schenk, Ferdinando De Vita, Evaristo Maiello, Timo Gaiser, Disorn Sookthai, Ulli Simone Bankstahl, Claudia Pauligk, Thorsten Oliver Goetze, Nils Homann
Journal: Journal of Clinical Oncology (2020)

4501 Background: Periop. FLOT has become SOC for resectable, esophagogastric adenocarcinoma. However, patient’s outcome is still poor. This trial evaluates the addition of the VEGF-R2 inhibitor ramucirumab (RAM) to FLOT for resectable patients (pts). Methods: This is a prospective, international, randomized, investigator-initiated phase II/III trial. Pts with resectable, Her2-negative, adenocarcinoma of the stomach and GEJ (≥ cT2 or cN+) were enrolled. Pts were randomized to 4 pre-and post-operative cycles of FLOT (docetaxel 50 mg/m²; oxaliplatin 85 mg/m²; leucovorin 200 mg/m²; 5-FU 2600 mg/m², q2w) alone (Arm A) or the same regimen with RAM 8mg/kg q2w, followed by 16 cycles RAM (Arm B, FLOT-RAM). Important endpoints of phase II (exploratory) were major pathological (complete and nearly complete) response, centrally assessed acc. to Becker criteria, R0-resection rate, and safety. GEJ type I tumors and pts requiring trans-thoracic esophagectomy were excluded for safety reasons during the conduct of the study. Results: In total, 180 pts were randomized. Baseline characteristics were similar between arms (male, 73%; median age, 60y; cT3/T4, 83%; cN+, 78%; GEJ, 54%; signet-ring cells, 40%). However, the FLOT-RAM arm included more unfavorable pts with T4 (9% vs. 4%), Siewert type I tumors (18% vs. 13%), impaired ECOG PS of 1 (34% vs. 20%), and concomitant disease (87% vs. 79%). 91% of pts with FLOT and 92% with FLOT-RAM completed the 4 pre- cycles. R0-resection (in the full set) could be achieved in 83% of pts with FLOT and 97% of pts with FLOT-RAM (p = 0.0049). The rate of major path response was similar in both arms and was 30% for FLOT and 27% for FLOT-RAM. Surgical morbidity was observed in 37% of pts with FLOT and 44% of pts with FLOT-RAM. Mortality was 2.5% with FLOT and 5.9% with FLOT-RAM including GEJ type I tumors and dropped to 2.9% in both arms after excluding type I tumors per amendment. There was bit more G≥3 adverse events with FLOT-RAM (78% vs. 89%). Conclusions: In this phase II trial, the addition of ramucirumab to perioperative FLOT significantly improved R0-resection rates without an impact on path response, mainly because more patients could proceed to operation. The FLOT-RAM is safe, when type I tumors are excluded. Clinical trial information: NCT02661971 .
中成药在心血管疾病中的合理应用
Authors: 尹德海
Journal: BMJ (2009)

根据卫生部 发布的数据,脑血管疾病和心脏病分别位于我国城乡居民死因构成比的第二位和第三位[1],若将两者相加,则超过居于第一位的恶性肿瘤.在我国心血管疾病的临床治疗中,中成药的使用很普遍,在综合性医院中,西医医师所开出的中成药远远超过中医医师[2].中成药是按照中医理论进行组方,只有在中医理论的指导下才能得到合理应用.对于西医医师,在使用中成药时应该对中医的一些理论有所了解,不能完全按照某种中成药适用于某种疾病的思路用药。
Enhancer Reprogramming within Pre-existing Topologically Associated Domains Promotes TGF-β-Induced EMT and Cancer Metastasis
Authors: Yunbo Qiao, Zejian Wang, Fangzhi Tan, Jun Chen, Jianxiang Lin, Jie Yang, Hui Li, Xiongjun Wang, Andrej Sali, Liye Zhang, Guisheng Zhong
Journal: Molecular Therapy (2020)

Transcription growth factor β (TGF-β) signaling-triggered epithelial-to-mesenchymal transition (EMT) process is associated with tumor stemness, metastasis, and chemotherapy resistance. However, the epigenomic basis for TGF-β-induced EMT remains largely unknown. Here we reveal that HDAC1-mediated global histone deacetylation and the gain of specific histone H3 lysine 27 acetylation (H3K27ac)-marked enhancers are essential for the TGF-β-induced EMT process. Enhancers gained upon TGF-β treatment are linked to gene activation of EMT markers and cancer metastasis. Notably, dynamic enhancer gain or loss mainly occurs within pre-existing topologically associated domains (TADs) in epithelial cells, with minimal three-dimensional (3D) genome architecture reorganization. Through motif enrichment analysis of enhancers that are lost or gained upon TGF-β stimulation, we identify FOXA2 as a key factor to activate epithelial-specific enhancer activity, and we also find that TEAD4 forms a complex with SMAD2/3 to mediate TGF-β signaling-triggered mesenchymal enhancer reprogramming. Together, our results implicate that key transcription-factor (TF)-mediated enhancer reprogramming modulates the developmental transition in TGF-β signaling-associated cancer metastasis. Transcription growth factor β (TGF-β) signaling-triggered epithelial-to-mesenchymal transition (EMT) process is associated with tumor stemness, metastasis, and chemotherapy resistance. However, the epigenomic basis for TGF-β-induced EMT remains largely unknown. Here we reveal that HDAC1-mediated global histone deacetylation and the gain of specific histone H3 lysine 27 acetylation (H3K27ac)-marked enhancers are essential for the TGF-β-induced EMT process. Enhancers gained upon TGF-β treatment are linked to gene activation of EMT markers and cancer metastasis. Notably, dynamic enhancer gain or loss mainly occurs within pre-existing topologically associated domains (TADs) in epithelial cells, with minimal three-dimensional (3D) genome architecture reorganization. Through motif enrichment analysis of enhancers that are lost or gained upon TGF-β stimulation, we identify FOXA2 as a key factor to activate epithelial-specific enhancer activity, and we also find that TEAD4 forms a complex with SMAD2/3 to mediate TGF-β signaling-triggered mesenchymal enhancer reprogramming. Together, our results implicate that key transcription-factor (TF)-mediated enhancer reprogramming modulates the developmental transition in TGF-β signaling-associated cancer metastasis.
Clinical, radiologic &amp; prognostic profile of IDH wild type diffuse astrocytic glioma with molecular features of glioblastoma.
Authors: Oluwatosin Akintola, Wesley Samore, Maria Martinez-Lage Alvarez, Elizabeth Robins Gerstner
Journal: Journal of Clinical Oncology (2020)

2557 Background: In 2018, The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) recommended that IDH-wildtype diffuse astrocytic glioma Grade II/III with either EGFR amplification, combined whole chromosome 7 gain and whole chromosome 10 loss (+7/−10), or TERT promoter mutation should receive an integrated histological and molecular grade classification: Diffuse astrocytic glioma, IDH-wildtype with molecular features of glioblastoma, WHO grade IV. The natural history, radiologic characteristics and standard management for these patients has not been well described. They are typically excluded from clinical trials for WHO Grade IV gliomas. Methods: Adults diagnosed at Massachusetts General Hospital with IDH wildtype diffuse astrocytoma and EGFR amplification or TERT promoter mutation from 2011-2019 were identified. Demographics, functional status, radiologic features, MGMT promoter methylation status, time to progression, and overall survival were collected retrospectively. Qualitative MRI data was analyzed using the VASARI feature set. Response assessment was performed using the RANO criteria. Results: 50 patients were identified (table). 37/50 patients received standard Stupp protocol, 2/50 received hypofractionated radiotherapy with temozolomide, 6/50 received radiotherapy alone, and 1 patient received a MEK inhibitor. None were enrolled in clinical trials at diagnosis. mPFS was 10 months in the 47/50 with confirmed progression and mOS in the patients with confirmed deaths (40/50) was 17.5 months (4-47). 9/50 patients are alive with survival ranging 6-52 months. Conclusions: Outcomes for patients with molecularly defined GBM were variable. Analysis of the cohort to characterize factors that led to the observed variability is in progress. More studies on molecularly defined glioblastomas are required to better understand their behavior and to provide guidance for their inclusion or exclusion in clinical trials. [Table: see text]
Preliminary studies on establishment of indicator system to evaluate basic capacities of trainers of training for community general practitioners in Shanghai
Authors: Yuan Zhang, Hua Yang, Tian-hao Wang, Shan-zhu Zhu
Journal: BMJ (2011)

Objective To explore establishment of indicator system to evaluate basic capacities of trainers of training for community general practitioners (GPs) to standardize their capacity building and management.Methods Questionnaire survey was conducted among 190 trainers of training for community health managers and GPs who were involved in community health-care and health-care service management in 12 districts of Shanghai to investigate what basic capacities the trainers should have.Delphi expert consultation method was used to construct an evaluation indicator system.Firstly, an evaluation form was formulated based on the preceding questionnaire.Then, two rounds of expert consultation were carried out with 28 experts specialized in general practice, training for GPs, public health and health management.The last step was to set up an evaluation indicator system based on experts' opinions with statistical analysis.Results The newly-established system consisted of five first-grade indicators including comprehensive performance, capacities and personal willingness, background of education and career, personal potential for professional development, capacity in general practice and capacity in training for GPs, and 57 second-grade indicators.Activity coefficient of the experts was all 100%, authority coefficients of the experts were 0.85,and harmonious coefficient of importance of the evaluation was 0.190 and 0.225 ( all P ＜ 0.01 ),respectively, in two rounds of Delphi consultation.Conclusions The preliminarily established indicator system to evaluate capacities of trainers of training for community GPs in diverse aspects can be used as reference for quality critria in selection of trainers of training for community GPs.

Key words: 
Education, medical, continuing;  General medicine;  Clinical competence;  Delphi technique;  Evaluation studies
Multi-slice computed tomographic coronary angiography in diagnosis of chronic total occlusion of coronary artery
Authors: Jianfei Ye, Yuxiang Dai, Chenguang Li, Hao Lu, Shufu Chang, Junbo Ge
Journal: BMJ (2016)

Objective
To evaluate the application of multi-slice computed tomographic coronary angiography in diagnosis of chronic total occlusion (CTO) of coronary artery.


Methods
Six hundred and thirty eight patients were diagnosed as CTO disease with coronary angiography (CAG) from June 2011 to December 2012 in Zhongshan Hospital; 236 of them received multi-slice computed tomographic coronary angiography in 60 days before.


Results
In total 708 vessels of the 236 patients, 244 vessels were proved totally occluded, 128 (52.5%) of which were located in left anterior descending artery, 31 (12.7%) were located in left circumflex coronary artery and 85 (34.8%) located in right coronary artery. Multi-slice computed tomographic coronary angiography was superior to CAG in judgment of stump anatomy (64.3% vs. 52.5%, F=7.09, P=0.010), plaque calcification (40.2% vs. 26.2%, F=10.68, P=0.001) and distal vessel interpretability (93.9% vs. 74.6%, F=34.06, P 0.05).


Conclusion
Multi-slice computed tomographic coronary angiography provides more detailed anatomy information of CTO lesions and is of value in diagnosis and treatment of CTO lesions.


Key words: 
Tomography; Angiography; Coronary occlusion
伴有变应性肉芽肿性血管炎表现的血管免疫母细胞性T细胞淋巴瘤一例
Authors: 叶华, 余洁, 栗占国
Journal: BMJ (2008)

变应性肉芽肿性血管炎或称Churg-Stgauss综合征(CSS)是一种主要表现为变应性鼻炎、哮喘和嗜酸细胞浸润的坏死性小血管炎;血管免疫母细胞性T细胞淋巴瘤(AITL)是一类来源于成熟T细胞的恶性肿瘤.上述两种疾病均为临床少见病,本文介绍一例伴有CSS临床表现的AITL。
乳腺疾病基础知识（四）：早期乳腺癌的内科治疗（IV）：新辅助治疗
Authors: Ian, Smith, Susan, Chua, 王佳玉（译, 徐兵河（校）
Journal: BMJ (2006)

术前对可手术乳腺癌进行新辅助治疗（又称术前治疗）的主要临床目的是降低肿瘤分期，减少根治术的比率。辅助治疗的临床试验往往需斥巨资，并且耗时数年才能完成，而小规模新辅助治疗的临床试验将体内原发肿瘤作为观察指标，短期内通过肿瘤对治疗敏感性的分析（包括临床、病理、生物学特点）即可准确地预测长期疗效。