tbuckley/cabot-search huggingface dataset:
Lisocabtagene maraleucel (liso-cel) for treatment of second-line (2L) transplant noneligible (TNE) relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphoma (NHL): Updated results from the PILOT study.
Authors: Alison R. Sehgal, Gerhard Hildebrandt, Nilanjan Ghosh, John E. Godwin, Nina D. Wagner-Johnston, Daanish Hoda, Edward J. Licitra, Javier Munoz, Nikolaus S. Trede, Lei Wang, Jerill Thorpe, Leo I. Gordon
Journal: Journal of Clinical Oncology (2020)

8040 Background: Patients (pts) with aggressive large B-cell NHL who are R/R after first-line immunochemotherapy and not eligible for high-dose chemotherapy and HSCT have a poor prognosis and no established standard of care. The ongoing, open-label phase 2 PILOT study is the first to assess the safety and efficacy of liso-cel, an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product infused at equal target doses of CD8+ and CD4+ CAR+ T cells, as 2L therapy in TNE pts (NCT03483103). Methods: Eligible pts had aggressive R/R diffuse large B-cell lymphoma NOS (de novo or transformed follicular lymphoma [FL]), high-grade B-cell lymphoma, or FL grade 3B with 1 line of prior therapy containing an anthracycline and anti-CD20 agent. Pts were deemed TNE by meeting ≥1 criteria: age ≥70 y, ECOG PS 2, or impaired organ function (DLCO ≤60% [but SaO 2 ≥92% and CTCAE ≤1 dyspnea], LVEF ≥40% to &lt; 50%, creatinine clearance &gt; 30 to &lt; 60 mL/min, or AST/ALT &gt; 2 to ≤5 × ULN). Liso-cel (100 × 10 6 CAR+ T cells) was administered 2–7 days after lymphodepletion (LD) with fludarabine/cyclophosphamide. The primary endpoint is ORR; key secondary endpoints are AEs and CR rate. Results: At data cutoff, 25 pts had LD followed by liso-cel infusion. Pt characteristics are summarized in the Table. Overall, 48% (n = 12) had high tumor burden and 48% were primary refractory. 18/25 (72%) pts had grade ≥3 treatment-emergent AEs, 40% of which were cytopenias. No grade 5 AEs occurred within the first 30 days after liso-cel. Five pts (20%) had cytokine release syndrome (CRS) and 3 (12%) had neurological events (NEs). No grade 3/4 CRS was observed; 2 pts (8%) had grade 3/4 NEs. Five pts (20%) received tocilizumab and/or dexamethasone for CRS/NEs. At a median follow-up of 3.5 mo, the ORR was 80% (95% CI, 59–93; n = 20); 48% of pts (n = 12) achieved CR. Conclusions: These interim data suggest that elderly and/or comorbid pts with R/R aggressive large B-cell NHL, who are not eligible for high-dose chemotherapy and HSCT, can receive 2L liso-cel with similar safety and efficacy to 3L+ pts as previously reported (Abramson, ASH 2019 #241). Updated data with longer follow-up will be presented. Clinical trial information: NCT03483103 . [Table: see text]
嗜酸细胞肉芽肿一例
Authors: 李苓, 王利利
Journal: BMJ (2008)

患者男,32岁,因右面颊部肿物10年,于2007年3月收入院.患者于10年前无意中发现右侧面颊部一肿物,大小约1.0 cm×1.0 cm,肿物时大时小,偶有面部发痒.在当地医院一直按慢性淋巴结炎治疗,症状无改善.近1年该肿物逐渐增大.既往无寄生虫病史及食物、药物过敏史.20年前患肾病综合征,已治愈。
Changes and significance of serum glial fibrillary acidic protein (GFAP) in patients with Parkinson disease
Authors: Wen Su, Hai-bo Chen, Shu-hua Li
Journal: BMJ (2008)

Objective To investigate changes in serum level of glial fibrillary acidic protein (GFAP) in patients with Parkinson disease (PD) and its clinical significance. Methods Serum GFAP was determined with sandwich ELISA for 82 patients with PD and acute cerebral infarction (ACI), as well as healthy normal controls. Patients with PD were then divided into two sub-groups in terms of their course duration, one with less than five years and the other with more than or equal to five years. Effects of course duration and age of the patients on their serum GFAP were analyzed. Results Serum level of GFAP was significantly higher in patients with PD [(1.628±0.104) μg/L] and ACI [(1. 637±0. 063 )μg/L] than that in healthy normal controls [ (0. 025±0. 003)μg/L, t = 82. 7, 142. 2, all P   0. 05 ). Serum level of GFAP in PD patients had no significant correlation with their age. There was no significant difference in serum GFAP between two sub-groups of patients with PD (P > 0.05 ). Conclusions Serum level of GFAP increased significantly in PD patients, as compared to healthy normal controls, but it is not specific. Serum GFAP in patients with PD maintained at certain high level with progression of the disease, indicating effect of astrocytes may persistently exist during the disease course.

Key words: 
Parkinson diseases;  Glial fibrillary acidic protein;  Brain infarction
Aspirin attenuates YAP and β-catenin expression by promoting β-TrCP to overcome docetaxel and vinorelbine resistance in triple-negative breast cancer.
Authors: Ji Ma, Hongwei Xia, Zhenhai Fan, Qiulin Tang, Tao Zhang, Feng Bi
Journal: Journal of Clinical Oncology (2020)

e13099 Background: YAP and β-catenin play critical roles in the carcinogenesis of several cancers, but their functions in chemoresistance remain unclear in triple-negative breast cancer (TNBC). Herein, we examined the expression and function of the two proteins in the chemoresistance of TNBC. Methods: We examined the expression levels of YAP and β-catenin in TNBC samples by immunohistochemistry (IHC) and their roles in prognosis. Dynamic changes in the two proteins in TNBC tissues were determined by RT-PCR. CCK-8 assays, colony formation assays, flow cytometry, migration assays and nude mouse models were used to investigate the functions of YAP and β-catenin in drug-resistant TNBC cells. The involved signalling pathways were detected by western blot assays. Results: TNBC patients with high YAP and/or β-catenin expression had a higher risk of relapse or mortality than patients with low YAP and/or β-catenin expression, and changes in the expression of the two proteins might be a promising predictive biomarker for neoadjuvant chemotherapy sensitivity. Inhibition of YAP or β-catenin enhanced the cytotoxicity of the anti-microtubule agents docetaxel and vinorelbine against TNBC cells in vitro and in vivo. Moreover, YAP and β-catenin were upregulated in docetaxel- or vinorelbine-resistant TNBC cells, while inhibition of YAP or β-catenin enhanced the sensitivity of drug-resistant cells. Interestingly, aspirin, a kind of acetylsalicylic acid, reversed the drug resistance of cells and in combination with aspirin and docetaxel or vinorelbine significantly inhibited the growth of drug-resistant TNBC cells. The involved mechanism is that aspirin impaired YAP or β-catenin expression by upregulating the E3 ubiquitin ligase β-TrCP. Conclusions: Both YAP and β-catenin act as key biomarkers of prognosis and anti-microtubule drug resistance in TNBC, and the combined use of aspirin and anti-microtubule drugs inhibits YAP and β-catenin, presenting several promising therapeutic approaches for TNBC treatment.
Assessing patient satisfaction after comprehensive medication review including oral chemotherapy adherence with an oncology pharmacist at the Southcoast Centers for Cancer Care (SCCC).
Authors: Patrick John Skeffington, Laura Haynes, Donna Raymond, Heather McCarthy
Journal: Journal of Clinical Oncology (2020)

e19241 Background: Use of oral chemotherapy has increased dramatically over the past few years. Patient often are required to obtain their oral chemotherapy from a third party specialty pharmacy while continuing to receive their other medications from other pharmacies. Many community pharmacists lack knowledge about oral chemotherapy, safe practices, or effective counseling of these medications. Objective: To assess patient perception and satisfaction of a pharmacist 1 on 1 appointment when starting oral chemotherapy. Methods: A program was designed at SCCC whereby all patients starting oral chemotherapy are scheduled for an appointment with a clinical oncology pharmacist to update medication lists, evaluate adherence, and conduct a "brown bag" visit where patients are allowed to voice concerns and ask questions. After each appointment patients were asked to fill out a short survey, The Patient Satisfaction with Pharmacist Services Questionnaire (PSPSQ 2.0). Results: PSPSQ 2.0 uses a Likert scale ranging from 1 to 4. From October 2016 to June 2019, 174 patients had appointments and 55 returned their surveys yielding a 30% response rate. Average scores hovered around 1 (strongly agree) for each question except question 11 (the only negatively worded question). Question 11 averaged 3.1; Disagree. Conclusions: Patients who were seen by an oncology clinical pharmacist to evaluate adherence, participate in a "brown bag" clinic and open discussion, found the appointment worthy of their time.
<sup>89</sup>Zr-durvalumab PD-L1 PET in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck.
Authors: Sarah Verhoeff, Pim P van de Donk, Erik H.J.G. Aarntzen, Iris Harriëtte Cornelia Miedema, Sjoukje Oosting, Jens Voortman, Adrienne H. Brouwers, Marije Slingerland, Sandra Heskamp, Carla M.L.- Van Herpen
Journal: Journal of Clinical Oncology (2020)

3573 Background: Immune checkpoint inhibitors (ICI) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have shown activity in R/M squamous cell carcinoma of the head and neck (SCCHN). Positron-emission-tomography (PET) with 89 Zr-labeled anti-PD-L1 antibodies could aid in predicting response to ICI. We present the dose-finding results of the first-in-human 89 Zr-durvalumab PD-L1 PET-imaging in patients with SCCHN participating in the ongoing phase II PINCH study (NCT03829007). Methods: Following baseline [ 18 F]FDG-PET and CT/MRI imaging, patients with incurable R/M SCCHN received 37 MBq 89 Zr-durvalumab and protein dose 2mg, 10mg or 50mg durvalumab. 89 Zr-durvalumab PD-L1 PET-scan was acquired day 5 post-injection. Plasma pharmacokinetic analyses were performed at day 0 and 5. Standardized uptake values (SUV, mean ± SD) were measured in [ 18 F]FDG-positive tumor lesion, liver, spleen, bone marrow and bloodpool. PD-L1-expression was assessed on archival tumor tissue using the Ventana PD-L1 (SP263) assay. Results: 14 patients were enrolled and no adverse events were reported. High tracer-retention was observed in liver and spleen, most prominent in patients receiving 2 or 10mg durvalumab. 89 Zr-durvalumab accumulation within tumors and between patients was heterogeneous and not all [ 18 F]FDG-positive lesions showed 89 Zr-durvalumab uptake. Tumor lesions were visualized best using 10 or 50mg durvalumab (SUV peak 2mg: 3.86 ± 0.79, 10mg: 7.46 ± 2.18, 50mg: 5.57 ± 1.74). Tumor-to-blood-ratios for 10mg durvalumab were highest (2mg: 2.27 ± 0.33, 10mg: 3.44 ± 0.76, 50mg: 1.73 ± 0.99; p = 0.019). PK-analyses confirmed visual prolonged tracer-retention in bloodpool with increasing protein dose. PD-L1-expression was equally distributed amongst dose-groups. Conclusions: This is the first study to show feasibility of 89 Zr-durvalumab PD-L1 PET in SCCHN patients, demonstrating the highest tumor-to-blood radio with a total dose of 10mg durvalumab. So far, no correlation of tumor PD-L1 expression with 89 Zr-durvalumab-uptake and PD-L1 expression on archival tissue was found. Next step will be to correlate 89 Zr-durvalumab PD-L1 PET tumor uptake with durvalumab treatment response in the phase 2 part of the PINCH study. Clinical trial information: NCT03829007 .
Association of Stay-at-Home Orders With COVID-19 Hospitalizations in 4 States
Authors: Soumya Sen, Pinar Karaca-Mandic, Archelle Georgiou
Journal: JAMA (2020)

An Pan, PhD; Li Liu, MD, PhD; Chaolong Wang, PhD; Huan Guo, MD, PhD; Xingjie Hao, PhD; Qi Wang, MD, PhD; Jiao Huang, PhD; Na He, PhD; Hongjie Yu, PhD; Xihong Lin, PhD; Sheng Wei, MD, PhD; Tangchun Wu, MD, PhD
上海市新型农村合作医疗运作的模式与评价
Authors: 王卫华, 张文忠
Journal: BMJ (2007)

农村卫生工作是三农问题的组成部分,是构建和谐社会的重要内容.本研究以福利经济学的视角,根据上海市卫生局基层卫生处2006年工作总结及其他相关文献的数据,从上海市农村卫生公共物品的生产供给、公共物品的总体评价、公共政策目标确定与存在问题、公共服务体系的完善与固化4个方面,分析上海市新型农村合作医疗(新农合医疗)农村卫生工作的成绩与问题,为建立新型各司其职的公共服务体系提供参考性建议。
Medicalising and medicating unhappiness
Authors: Christopher Dowrick, Allen Frances
Journal: BMJ (2013)

Objectives
Cardioankle vascular index (CAVI) is a new index of arterial stiffness independent of immediate blood pressure. Homocysteine (Hcy) is an independent risk factor for vascular diseases. The aim of this study was to investigate the relationship between Hcy and CAVI in the vascular-related diseases.


Design
Descriptive research.


Participants
88 patients (M/F 46/42) with or without hypertension, coronary artery disease or arteriosclerosis obliterans were enrolled to our study. They were divided into two groups according to the level of Hcy.


Methods
CAVI, carotid-femoral pulse wave velocity (CFPWV) and carotid-radial pulse wave velocity (CR-PWV) were measured by VS-1000 and Complior apparatus.


Results
There was significant correlation between Hcy and CF-PWV, CR-PWV, CAVI in the entire group (r=0.33, P=0.002; r=0.51, P<0.001; r=0.42, P<0.001, respectively). And there was significant correlation between Hcy and CF-PWV, CR-PWV, CAVI in the vascular-related disease group (r=0.23, P=0.048; r=0.51, P<0.001; r=0.392, P= 0.001, respectively). The level of Hcy was significantly higher in patients with one or more vascular diseases than in patients without vascular diseases. The levels of CF-PWV, CR-PWV and CAVI were significantly higher in Hcy ≥15 μmol/L group than in Hcy<5 μmol/L group (13.7±3.0 vs 10.8±2.5, P< 0.001; 10.6±2.1 vs 9.2±1.6, P=0.001; 9.30±2.1 vs 7.79±2.1, P= 0.001, respectively). Multiple linear regression showed that Hcy, body mass index (BMI) and age were independent associating factors of CAVI in the entire study group (β=0.421, P=0.001; β=-0.309, P=0.006; β=0.297, P=0.012, respectively). And Hcy, BMI and age were independent influencing factors of CAVI in the vascular-related disease group (β=0.434, P=0.001; β=-0.331, P=0.009; β=0.288, P=0.022, respectively).


Conclusions
CAVI was positively correlated with Hcy in the vascular-related diseases.
PIQMEE: Bayesian Phylodynamic Method for Analysis of Large Data Sets with Duplicate Sequences
Authors: Veronika Boskova, Tanja Stadler
Journal: Molecular Biology and Evolution (2020)

Next-generation sequencing of pathogen quasispecies within a host yields data sets of tens to hundreds of unique sequences. However, the full data set often contains thousands of sequences, because many of those unique sequences have multiple identical copies. Data sets of this size represent a computational challenge for currently available Bayesian phylogenetic and phylodynamic methods. Through simulations, we explore how large data sets with duplicate sequences affect the speed and accuracy of phylogenetic and phylodynamic analysis within BEAST 2. We show that using unique sequences only leads to biases, and using a random subset of sequences yields imprecise parameter estimates. To overcome these shortcomings, we introduce PIQMEE, a BEAST 2 add-on that produces reliable parameter estimates from full data sets with increased computational efficiency as compared with the currently available methods within BEAST 2. The principle behind PIQMEE is to resolve the tree structure of the unique sequences only, while simultaneously estimating the branching times of the duplicate sequences. Distinguishing between unique and duplicate sequences allows our method to perform well even for very large data sets. Although the classic method converges poorly for data sets of 6,000 sequences when allowed to run for 7 days, our method converges in slightly more than 1 day. In fact, PIQMEE can handle data sets of around 21,000 sequences with 20 unique sequences in 14 days. Finally, we apply the method to a real, within-host HIV sequencing data set with several thousand sequences per patient.
Potential use of homologous recombination deficiency score as an indicator of therapy selection in leiomyosarcoma patients.
Authors: Yuhong Zhou, Xi Guo, He Guo, Rongyuan Zhuang, Wenshuai Liu, Yong Zhang, Hanxing Tong, Zhiming Wang, Yan Wang, Chentao Lv, Weiqi Lu, Chun Dai, Jun Liu
Journal: Journal of Clinical Oncology (2020)

e23539 Background: Leiomyosarcoma (LMS) is one of the most frequent sarcoma subtypes. While surgical resection is the standard treatment of LMS, chemotherapy and radiation have shown additional survival benefit. However, the treatment response is variable and selection of appropriate agents is difficult due to the great heterogeneity of LMS. Matching DNA damaging reagents or PARP inhibitors, to tumors with a general homologous recombination deficit (HRD), can help to deploy these reagents more precisely. We explored the correlation of HRD score with the activation of PARP signaling pathway and retrospectively tested the effect of platinum-based therapy on an LMS patient with high HRD score. Methods: Nineteen LMS samples were subjected to whole exome sequencing and their HRD scores were calculated using a published algorithm. Nine of the LMS samples were also subjected to RNA-seq analysis and undergone GSEA to profile PARP pathway expression. CIBERSORT was employed to profile infiltrating immune cells. Results: The 19 LMS samples are defined as HRD-high (11 samples) or HRD-low (8 samples) if their HRD score is above or equal to, or below the medium respectively. For the 9 samples undergone RNA-seq, 97 genes have differential expression between the two groups (p-value &lt; 0.05, fold change≥ 2). GSEA revealed 23 enriched pathways. Interestingly, PPAR signaling pathway is the most highly enriched one (EnrichmentScore = 0.506, P.adj = 0.005). No other pathogenic germline or somatic mutation in HRD related genes, for example BRCA1/2, is enriched. Additionally, high HRD score is significantly correlated with infiltrating Tregs, monocyte, and M0 macrophages as found in CIBERSORT analysis. To retrospectively test whether HRD score can be used to predict the response to inhibitors of DNA repair pathway, we identified one patient who had received platinum-based combination therapy after failure of first-line chemotherapy. The patient is a 40-year-old female with stage IV LMS and has a high HRD score. She achieved PR with 6-month PFS and remains progression free up to the abstract date, supporting a good correlation between high HRD score and advanced chemotherapy in LMS patients. Conclusions: High HRD score is correlated with activated PPAR pathway and infiltrating Tregs, monocytes and M0 macrophages, and can potentially be used to identify LMS patients with good response to platinum-based chemotherapy even though they have no obvious germline and somatic mutation in genes involved in DNA repair.
Establishment of assessment criteria for general practitioner trainers in clinical training base
Authors: Sunfang Jiang, Hua Yang, Juan Shou, Xiangjie Zhang, Minghui Peng
Journal: BMJ (2015)

Objective
To develop an assessment criteria for general practitioner (GP) trainers in clinical training base.


Methods
Based on the extensive literature review and expert interview, a preliminary index system was established with 4 first-grade indicators and 45 second-grade indicators for GP trainers in clinical training base. During 2012 to 2013, a two-round Delphi consultation was conducted to establish the assessment criteria.


Results
Thirty seven experts engaged in clinical practice, training and managers of GP training program from clinical training bases, medical schools, or health bureau in Shanghai were invited for Delphi consultation. Among them 64.8 (24/37)% were engaged in GPs training over 5 years, 78.4%(29/37) worked as GP trainers, 70.2%(26/37) with high-level professional title. In two round consultations, the activity coefficient of the experts were 97.3% and 100.0%, authority coefficient were 0.817 and 0.855, and harmonious coefficient of importance of the evaluation were 0.188 (P<0.01) and 0.278 (P<0.01), respectively. The opinions among the experts were consistent from the first round to the second round. The assessment criteria for GP trainers in clinical training bases was established with 4 first-grade indicators and 27 second-grade indicators. The 4 first-grade indicators were professionalism, clinical practice components, teaching quantity & components, basic conception of general practice, with weight coefficient of 0.253, 0.253, 0.251 and 0.243, respectively.


Conclusion
The established assessment criteria for GP trainers is credible and comprehensive, which can be applied in evaluating the comprehensive capacity of trainers in clinical training bases.


Key words: 
Teacher training; Criteria; Delphi technique; General practitioners
A case of thyrotropin-secreting pituitary adenoma treated with long-acting octreotide formulation
Authors: Xiao-ping Chen, Xin Wang, Xiao-yan Xing, Yi Lu, Guang-wei Li
Journal: BMJ (2011)

A 56-year-old man with 1-year history of palpitation, heat intolerance and sweating, was diagnosed as thyrotropin (TSH) -secreting pituitary adenoma based on the symptoms of hypermetabolism, enlarged thyroid gland, inappropriately increased serum TSH concomitantly elevated plasma thyroid hormones and a pituitary tumor demonstrated on magnetic resonance imaging. Long-acting octreotide formulation was administered at a dose of 20 mg intramuscularly. Tumor volume shrinkage and improvement of thyroid function was achieved after a single drug injection; and the thyroid function returned to normal in 28 days. It is suggested that long-acting octreotide formulation might be used as a routine therapeutic approach prior to pituitary surgery, which may enhance the effectiveness of surgery and postoperative recovery.

Key words: 
Pituitary neoplasms;  Octreotide
肝脾结核一例
Authors: 王雅凡, 吴小梅
Journal: BMJ (2005)

患者男,20岁.因咳嗽、咳痰、左胸痛、盗汗6个月,发热7 d入院.入院后体温37.2～39.2℃.体检:消瘦,颈部右侧扪及直径约15 mm淋巴结3个,活动,边界清楚,无触痛.两肺呼吸音无明显异常.肝肋下未及, 侧卧位脾肋下2 cm, 质中.实验室检查 :血红蛋白119 g/L.丙氨酸氨基转移酶74 U/L, 天冬氨酸氨基转移酶46 U/L, 谷酰转肽酶88 U/L,白蛋白32.7 g/L.红细胞沉降率28 mm/1 h.痰涂片抗酸杆菌(-)。
The impact of a precision medicine program on molecular testing rates for advanced non-small cell lung cancer (aNSCLC): Based on community-based provider survey assessment.
Authors: Natasha Clinton, Kashyap B. Patel, Susan Weidner
Journal: Journal of Clinical Oncology (2020)

e19179 Background: Rapid development in the Precision Medicine has provided oncologists the opportunity to offer individualized approaches to treat advanced non-small lung cancer(aNSCLC), one of the most devastating cancers, which until the past decade was thought to be invariably fatal within months. Despite superior outcomes associated with targeted therapy, most patients are not tested for all guideline-recommended molecular alterations. There is a need to educate and train health care providers (HCPs) and create standard testing patterns across the care continuum. Methods: We developed and launched a precision medicine program in January 2018 through the inception of a Precision Medicine Advisory Panel made up of community oncologists, oncology pharmacists and oncology nursing and research staff. The goal of our precision medicine program is to facilitate and drive the adoption of appropriate biomarker testing. To accomplish this, we focused on the development of testing recommendations and proactive HCP education. To evaluate the effectiveness of our program, improvements have been measured through annual audience response surveys of providers treating this patient cohort. Results: Year 1 less than 30% of survey participants were always requesting tissue-based molecular testing prior to starting first-line therapy. This increased to over 70% within an 15 month timeframe. Approximately 95% of respondents never or infrequently considered both tumor- and peripheral blood-based testing. Through the survey it was demonstrated that at least 25% are ordering both always or frequently. Timing of test results is very important within this patient population. In year 1, more than 50% of survey respondents would initiate therapy before the test results were received. The survey demonstrated significant improvement in Year 2, with more than 70% reporting never or rarely start therapy ahead of result availability. Conclusions: Although there has been demonstrated progress, areas for continued improvement exist. These include tissue allocation and payer coverage for molecular testing. Through continuing education and quality initiatives, we plan to maintain and demonstrate further improvements in testing adoption and appropriate utilization.