tbuckley/cabot-search huggingface dataset:
Tumour immune characterization in adenoid cystic carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures.
Authors: Shengjin Dou, Di Chen, Rongrong Li, Yining Yang, Ning He, Ge Jin, Jiang Li, Guopei Zhu
Journal: Journal of Clinical Oncology (2020)

e15191 Background: Here, we profiled genetic hallmarks of Chinese adenoid cystic carcinoma (ACC) patients and immune cells infiltration levels by gene expression-based computational methods to investigate the correlation with immunotherapy. Methods: 54 patients with pathologically confirmed ACC admitted from January 2016 to October 2019 were included. Mutation and expression profiles were obtained by whole-exome sequencing (WES) and RNA-seq, respectively. A nomogram that integrated clinicopathological features with the immune signature to predict recurrence or distant metastasis probability was constructed by multivariate Cox regression. Results: As expected, we observed MYB fusion and somatic mutations in our cohort (57%, 31/54), strengthening the role of these aberrations as critical events in ACC. Mutations in NOTCH1 were also found in our cohort (19%, 10/54). Median tumour mutational burden (TMB) of these patients is 0.85 Muts/Mbp (0-11 Muts/Mbp). Analysis of WES data showed that all patients were microsatellite instability (MSI)-negative, and 17 of them were confirmed by conventional MSI-PCR testing. Lack of PD-L1 expression is 96.0% (n = 46/48) at a tumour proportion score 0% and 22.9% (11/48) of cases showed more than 10% CD8+ prevalence. We compared cancer types using an immune infiltration score (IIS) and an antigen presenting machinery expression (APM) score and find that ACC is among the lowest for both scores. Statistically significant correlations were found between IIS and distant metastasis-free survival (univariate analysis, HR = 2.64, 95% confidence interval [CI], 1.134 to 6.145, p = 0.023). Patients with higher IIS had shorter distant metastasis-free survival time (log-rank p = 0.020), and patients with higher T cell infiltration score (TIS) had shorter locoregional recurrence-free survival time (log-rank p = 0.050). In addition, we investigated the pretreatment immune profile of five ACC patients treated with PD-1 checkpoint inhibitors, and found that both TIS and APM were elevated in responding patient (with a partial response to camrelizumab) whereas they were in the lowest for patients with progressive disease on camrelizumab or pembrolizumab. Conclusions: Our study highlights the immune infiltration patterns and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ACC.
Prevalence of autoimmune diseases in thymic epithelial tumors (TET) insights from RYTHMIC.
Authors: Jose Carlos Benitez, Marie Eve Boucher, Eric Dansin, Mallorie Kerjouan, Julien Mazieres, Eric Pichon, Francois Thillays, Pierre-Emmanuel Falcoz, Benoit Roch, Youssef Oulkhouir, Calcagno Fabien, Luc Thiberville, Christelle Clément Duchene, Franck Morin, Pascale Missy, Pascal Alexandre Thomas, Jean-Michel Maury, Thierry Molina, Nicolas Girard, Benjamin Besse
Journal: Journal of Clinical Oncology (2020)

9073 Background: TET are associated with autoimmune disorders (AID) in up to 30% of patients (pts). However, there have been wide variations in the reported prevalence of AID in TET pts in small single-center series. RYTHMIC (Réseau tumeurs THYMiques et Cancer) is a French network mandated to systematically discuss every case of TET. We aimed to describe the prevalence of AID in a large French population. Methods: RYTHMIC database, hosted by IFCT (Intergroupe Francophone de Cancérologie Thoracique), prospectively includes all consecutive pts with a diagnosis of TET discussed in French national or regional tumor boards. We analyzed epidemiologic, clinical and pathological characteristics of pts with TET’s related AID. Results: From January 2012 to December 2019, 2909 pts were included in the database. The mean age at diagnosis of TET was 54 and 52% were male. In the overall population, Masaoka Koga stages were well balanced with 12.6% (n = 187) stage I, 8.8% (n = 131) stage IIa, 8.4% (n = 124) stage IIb, 11.1% (n = 164) stage III and 8.5% (n = 125) stage IV. There were 364 (12.5%) events of AID in 302 pts. 62 pts (17%) had more than 1 AID. Among the events, 236 were myasthenia gravis (MG) (64.8%), 19 Hypo-gammaglobulinemia syndrome (5.2%), 15 pure red cell aplasia (4.1%), 18 thyroiditis (4.9%) and 16 systemic erythematous lupus (4.4%). Diagnosis of AID was mostly done at tumor diagnosis (n = 239, 65.7%) but some patient had AID diagnosed before diagnosis (n = 67, 18.4%) or during follow up (n = 32, 8.8%). Among pts presenting AID, B2 was the most common subtype (n = 133, 36.5%). The incidence of AID per subtype was as follow: A (n = 10/81, 12.3%), AB (n = 48/225, 21.3%), B1 (n = 35/130, 26.9%), B2 (n = 133/295, 45.0%), B3 (n = 46/113, 40.7%), thymic carcinoma (n = 16/275, 5.8%). Conclusions: The prevalence of AID in pts with TET was 12.5%, &gt; 40% in B2 and B3 subtypes. Diagnosis of AID can be delayed compared to the diagnosis of TET. Immunotherapy indication should be carefully assessed in pts with TET other than thymic carcinoma.
Effect of clinical competence training for general practitioners and influencing factors
Authors: Yao Liu, Sun-fang Jiang, Jie Gu, Juan Shou, Hui-ling Xia
Journal: BMJ (2013)

Objective
To evaluate the effect of clinical competence training for general practitioners in Shanghai.


Methods
Total 759 general practitioners participated in clinical competence training from July 2011 to October 2012 in Shanghai. The theoretical and practical operation scores of all the 759 trainees were compared before and after the training and the influencing factors of training effect were analyzed.


Results
The trainees, including 260(34.26%) males and 499 (65.74%) females, had average working experiences (13.6±7.1) years. The average total scores before and after training were(67.40±8.57)and (73.61±7.20) (t=17.96, P<0.01). The practical operation scores were improved more significantly, the average scores of physical examination before and after training were (12.90±3.76) and (14.00±3.51), scores of clinical skill before and after training were (9.41±4.80) and (13.40±4.02) (t=6.31 and 19.01, P<0.01). Among seven items of physical examination test, scores of four items(cardiopulmonary examination, abdominal examination, neurological examination and thyroid examination) were significantly higher than those before training (P<0.05 or <0.01). Scores of all 7 items of clinical skill test were higher than those before training (P<0.01). The main factors influencing the effect of training were gender, educational background, score before training and type of practice (P<0.01 or <0.05).


Conclusions
The clinical competence of general practitioners can be improved after the training. The training contents should be optimized in consistent with conditions of community health and general practitioners in the future.


Key words: 
General practitioner; Training; Clinical competence
Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma (NPC).
Authors: Robert John Walsh, Emily Pauline Nickles, Yating Li, Bhushan Dharmadhikari, Mickey Koh, Liam Pock Ho, Marieta Chan, Liang Piu Koh, Michelle Li Mei Poon, Lip Kun Tan, Yiqing Huang, Yvonne Li'en Ang, Wan Qin Chong, Yugarajah Asokumaran, Kwok Seng Loh, Ross A. Soo, Chwee Ming Lim, Herbert Schwarz, Boon Cher Goh
Journal: Journal of Clinical Oncology (2020)

6535 Background: Epstein-Barr virus (EBV) is associated with non-keratinising (NK) NPC, a disease prevalent in Southeast Asia, and provides a potential target for dendritic cell (DC) vaccine therapy. CD137 ligand (CD137L) expressed on antigen presenting cells costimulates CD137 expressing T cells upon receptor/ligand interaction. CD137L signalling differentiates monocytes to CD137L-DC, a novel type of DC, which are more potent than classical DC in stimulating autologous T cells. Here, we explore the safety and efficacy of autologous CD137L-DC pulsed with EBV peptides spanning Epstein Barr nuclear antigen 1, latent membrane protein 1 (LMP1) and LMP2 (CD137L-DC-EBV-VAX) in patients with locally recurrent or metastatic NPC. Methods: In this single centre, phase I study, eligible patients (pts) with locally recurrent or metastatic NK-NPC and clinical benefit (CB) from their prior treatment (stable disease [SD], partial [PR] or complete response[CR]), underwent apheresis to isolate monocytes which were differentiated to CD137L-DC through CD137L agonist exposure. CD137L-DC were pulsed with EBV antigens during maturation to obtain CD137L-DC-EBV-VAX which was administered intradermally every 2 weeks (w) for up to 7 injections following site preconditioning with Tetanus and Diphtheria vaccine. Results: 14 pts were enrolled of which 2 progressed rapidly and did not begin treatment. Mean age was 58 years. Median lines of prior treatment for metastatic NPC was 1 (range 1-6), the most common being cisplatin and gemcitabine. 9 pts received 7 vaccine doses (range 2-7) with a mean administered cell count of 23.9x10 6 . CB was seen in 5 cases (42%) with 1 PR and 4 SD beyond 1 year. Median progression free survival (mPFS) was 26w (95% CI, 23-43). The lowest PFS (8w) was in a pt with 6 prior lines of treatment including a checkpoint inhibitor. Mean pretreatment neutrophil: lymphocyte ratio (NLR) was 3.4 and a value of less than 3 was associated with prolonged mPFS (42 vs 14w, p = 0.01). Enzyme linked immune absorbent spot (ELISPOT) analysis in 5 pts with CB showed a rise in interferon-γ secreting peripheral T cells prior to the 3 rd vaccine versus baseline. Treatment was well tolerated with only 4 cases of grade 1 related adverse events reported, most commonly injection site reaction (3pts). Conclusions: CD137L-DC-EBV-VAX is safe and exhibits promising efficacy when administered following CB from chemotherapy. A rise in activated peripheral blood mononuclear cells after 2 vaccinations in selected patients showing benefit suggests immunological correlates with efficacy. Clinical trial information: NCT03282617 .
Prescriptions of antibiotics for children with upper respiratory infections in outpatient department
Authors: Yi Yuan, Ling Cao, Xuemei Yu
Journal: BMJ (2015)

The prescription of antibiotics for children with upper respiratory infections (URIs) in outpatient department of our hospital from November to December 2010 and from July to August 2011 were retrospectively analyzed. In 37 211 patient visits (prescriptions) with suppurative tonsillitis, laryngitis and other URIs, the antibiotic prescription rates were 90.45%(3 626/4 009), 78.77%(2 642/3 354) and 52.25%(15 596/29 848), respectively; the intravenous antibiotics rates were 78.22%(3 136/4 009), 60.58%(2 032/3 354) and 16.47%(4 915/29 848), respectively for above three conditions. For suppurative tonsillitis, the 3rd generation cephalosporins were the most commonly prescribed antibiotics (orally: 51.07%, 715/1 400) and (intravenously: 54.88%, 1 721/3 136), followed by the 2nd and first generation cephalosporins and macrolides. For laryngitis and other URIs, the 2nd generation cephalosporins were most frequently prescribed (orally: 48.78%, 538/1 103 and 39.16%, 4 433/11 320, respectively) and (intravenously: 54.38%, 1 105/2 032 and 42.75%, 2 101/4 915, respectively), followed by macrolides, 3rd generation cephalosporins and first generation cephalosporins. No intravenous penicillin were prescribed. Oral penicillin were prescribed for 0-0.22% of these children. The results indicate that antibiotics prescription rates are high for children with upper respiratory infections, particularly the prescription of broad spectrum antibiotics and intravenous antibiotics, while penicillin is seldom prescribed.

Key words: 
Respiratory tract infections; Anti-bacterial agents; Child
Pilot program of remote monitoring for high-risk patients on antineoplastic treatment.
Authors: Robert Michael Daly, Gilad Kuperman, Alice Zervoudakis, Alice Ro, Ankita Roy, Abigail Baldwin, Rori Salvaggio, Jessie C. Holland, Kimberly Chow, Tara Lauria, Margarita Rozenshteyn, Melissa Zablocki, Yeneat Ophelia Chiu, Nicholas Silva, Claire Perry, Stefania Sokolowski, Isaac Wagner, Brett A Simon, Diane Lauren Reidy, Wendy Perchick
Journal: Journal of Clinical Oncology (2020)

2027 Background: Early detection and management of symptoms in patients with cancer improves outcomes, however, the optimal approach to symptom monitoring and management is unknown. This pilot program uses a mobile health intervention to capture and make accessible symptom data for high-risk patients to mitigate symptom escalation. Methods: Patients initiating antineoplastic treatment at a Memorial Sloan Kettering regional location were eligible. A dedicated staff of RNs and nurse practitioners managed the patients remotely. The technology supporting the program included: 1) a predictive model that identified patients at high risk for a potentially preventable acute care visit; 2) a patient portal enabling daily ecological momentary assessments (EMA); 3) alerts for concerning symptoms; 4) an application that allowed staff to review and trend symptom data; and 5) a secure messaging platform to support communications and televisits between staff and patients. Feasibility and acceptability were evaluated through enrollment (goal ≥25% of new treatment starts) and response rates (completion of &gt; 50% of daily symptom assessments); symptom alerts; perceived value based on qualitative interviews with patients and providers; and acute care usage. Results: Between October 15, 2018 and July 10, 2019, the pilot enrolled 100 high-risk patients with solid tumors and lymphoma initiating antineoplastic treatment (median age: 66 years, 45% female). This represented 29% of patients starting antineoplastics. Over six months of follow-up, the response rate to the daily assessments was 56% and 93% of patients generated a severe symptom alert (Table). Both patients and providers perceived value in the program and 5,010 symptom-related secure messages were shared between staff and enrolled patients during the follow-up period. There was a preliminary signal in acute care usage with a 17% decrease in ED visits compared to a cohort of high-risk unenrolled patients. Conclusions: This pilot program of intensive monitoring of high-risk patients is feasible and holds significant potential to improve patient care and decrease hospital resources. Future work should focus on the optimal cadence of EMAs, the workforce to support remote symptom management, and how best to return symptom data to patients and clinical teams. [Table: see text]
论文撰写与临床工作紧密结合初见成效
Authors: 匡建华
Journal: BMJ (2006)

论文撰写是学术交流的手段,也是实现自我价值的途径之一.对于基层医务人员来说,要发表一篇论文是比较困难的事,我认为主要原因是缺乏系统管理和引导.近两年来,我院重症监护室通过加强论文撰写的管理,注重论文内容与临床工作的紧密衔接,不仅提高了论文的刊出率,而且促进了临床工作。
Early conservative eschar-scraping and delayed skin graft to cure deep burn on the face caused by coal-dust burning and blasting
Authors: 侯贺宪, 王立荣, 王强, 李保锴, 杨家保, 陈军, 闫军, 张劲光
Journal: BMJ (2007)

目的 探讨预防颜面部煤尘燃爆深度烧伤后严重毁容的治疗方法.方法 对12例煤尘燃爆颜面部深度烧伤患者,早期采用保守磨削痂、延期植皮和双眼睑早期减张、扩张创面立即植皮的处置方式进行治疗.结果 本组12例患者于伤后3周内创面全部愈合.随诊3个月,未发现明显瘢痕增生和畸形,面部表情自然,情绪表达充分.结论 应用早期保守磨削痂延期植皮的方法,可促进全颜面创面尽快修复,减少瘢痕增生和颜面畸形的发生。
Gosport must be a tipping point to fix professional hierarchies in healthcare
Authors: Darbyshire Philip, Thompson David, 沈玄韬, 张瑞明, 翁建平
Journal: BMJ (2019)

如果要杜绝类似Mid Staffordshire和Morecambe Bay的丑闻，所有医疗行业员工都应有权质疑各级同事的决策，并表达他们的担忧而不会受到任何报复，Philip Darbyshire和David Thompson写道。
Functional role of kallikrein 5 and proteinase-activated receptor 2 in eosinophilic esophagitis
Authors: Nurit P. Azouz, Andrea M. Klingler, Purnima Pathre, John A. Besse, Netali Ben Baruch-Morgenstern, Adina Y. Ballaban, Garrett A. Osswald, Michael Brusilovsky, Jeff E. Habel, Julie M. Caldwell, Mario A. Ynga-Durand, Pablo J. Abonia, Yueh-Chiang Hu, Ting Wen, Marc E. Rothenberg
Journal: Science Translational Medicine (2020)

Eosinophilic esophagitis is mediated by uncontrolled proteolytic activity of kallikrein 5 influencing the epithelial barrier and innate immunity.
Effectiveness of one-year community management for patients with chronic obstructive pulmonary disease
Authors: Fan Li, Xun Xu, Xuemin Zhang, Yingyun Cai, Wanghui Zhu, Huanying Fu, Chaoying Shen, Yunying Lu, Qijun Zhuang, Jianfeng Yin, Suhua Li, Weiwen Yin, Meihua Zhou, Xiaoli Chen
Journal: BMJ (2011)

Objective To evaluate effectiveness of prevention and treatment for patients with chronic obstructive pulmonary disease (COPD) for one year at community health-care service (CHS)centers. Methods A quasi-experiment design was used to evaluate effectiveness of community management for patients with COPD who visited and registered at Xiaokunshan and Xinbang CHS centers in Songjiang district of Shanghai in 2008, with COPD patients from Xiaokunshan community CHS center as management group and those from Xinbang as control. Measures for community management included training for local general practitioners in essential knowledge of COPD prevention and treatment, allocation of necessary drugs for COPD treatment, and health education for COPD patients and their family members. No special measures were taken for control group except routine treatment. Results A total of 132 patients were diagnosed as COPD according to their pulmonary function on 2008, 61 at Xiaokunshan and 71 at Xinbang CHS canters.One hundred and two patients, 47 at Xiaokunshan and 55 at Xinbang, finished one-year follow-up. Five patients from Xiaokunshan who were smokers at their first visits and three of them quitted smoking after oneyear management. Meanwhile, none of nine smoked patients from Xinbang quitted smoking in the same period. There was no statistically significant difference in symptom scores, pulmonary function, and forced expiratory volume at the first second (FEV1) between patients in the two groups during one-year follow-up.Average score of quality of life in patients at Xiaokunshan dropped to 39. 12 after one-year management from 46. 96 at their first visits, and that in patients at Xinbang increased to 62. 11 from 56. 55 (P＜0.01).Average six-minute walking distance (6-MWD) in patients at Xiaokunshan reduced to 354. 26 meters after one-year management from 361.66 meters at their first visits, meanwhile that in patients at Xinbang reduced to 351.18 meters from 398.07 meters (P =0. 008). Scores of functional dyspnea in patients at Xiaokunshan fell to 0.34 from 0.40 at their first visit, meanwhile that in patients at Xinbang increased to 1.00 from 0.95(P =0.038). During the one-year follow-up, 13 patients at Xiaokunshan and 53 at Xinbang visited emergency departments for treatment, and four at Xiaokunshan were hospitalized and none died, and five at Xinbang were hospitalized due to acute exacerbation of COPD and four of them died. Conclusions The study suggests that strengthening prevention and treatment for COPD patients at community level by general practitioners, patients themselves and their family members can improve their quality of life, reduce emergency visits and hospitalization, alleviate dyspnea symptoms and delay the decline of 6MWD.

Key words: 
Pulmonary disease, chronic obstructive;  Community health centers;  Disease management
Dominant negative PD1 armored CART cells to induce remission in relapsed or refractory non-Hodgkin lymphoma (NHL) patients.
Authors: Chengfei Pu, Liansheng Huang, Yang Su, Tianling Ding, Xibin Xiao, Lina Jin, Zhiyuan Cao, Ting Wu, Tong Chen, Luying Ding, Xiaohong Zhang, Haifeng Lan, Zhao Wu, Lei Xiao
Journal: Journal of Clinical Oncology (2020)

e15028 Background: The chimeric antigen receptor (CAR) T cell treatment has been demonstrated as an effective therapy to treat relapsed/refractory B cell malignancy. However, tumor microenvironment influences and affects the efficacy of CAR T treatment. For example, programmed death ligand 1/2 (PDL1/2) may inhibit the CAR T cells via interaction with up-regulated programmed cell death protein 1 (PD1) after T cells activation, suppressing the tumor-killing capability of the CAR T cells. Thus, blockade of the PD1-PDL1/2 interaction may enhance the anti-tumor efficacy of CAR T therapy. Methods: Here, we generated CAR T expressed an anti-CD19 CAR molecule and a dominant-negative PD1 molecule. Compared with conventional CART cells, these “armored” CART cells showed the enhanced capability of tumor-killing and more “memory-like” phenotypes after multiple-round tumor challenging. These results suggest dominant-negative PD1 molecules may protect CART cells from exhaustion in the tumor microenvironment. Results: Further, we reported the findings of a clinical trial for six relapsed or refractory B-cell non-Hodgkin lymphoma (NHLs) patients treated using our armored CAR T cells. These six patients failed multiple rounds of chemotherapy and radiotherapy. In the clinical trial, the patients were infused with autologous CAR T cells range from1×10 6 /kg to 8×10 6 /kg. PET/CT showed significant tumor shrinkage and SUV max declines in all six patients, and the ongoing responses were monitored. The best overall response rate (ORR)was 100%. Conclusions: The results of these six patients in the clinical trial showed that our armored CAR T cells achieved the significant anti-bulky lymphoma response while causing limited and tolerated cytokine release syndrome and central nervous system toxicity. Thus, dominant-negative PD1 molecules may increase CAR T cells persistence in patients, enhancing the efficacy of CAR T cells for treating blood cancer. Finally, dominant-negative PD1 can be used as a platform technology and may be applied to other adoptive cellular immunotherapies such as TCR-T or TIL in the treatment of solid tumors. We are continuing to monitor current patients and recruit more patients for the clinical trial.