tbuckley/cabot-search huggingface dataset:
Parameters of oxidative metabolism in the blood of patients with pancreatic tumors of different histotypes.
Authors: Irina A. Goroshinskaya, Elena M. Frantsiyants, Viacheslav A. Aleynov, Ludmila A. Nemashkalova, Natalia D. Cheryarina, Vladimir S. Trifanov, Stanislav S. Mezentsev, Fedor N. Grechkin, Maksim N. Duritskiy, Oleg I. Kit, Galina V. Zhukova, Yuriy A. Fomenko, Dmitry S. Petrov
Journal: Journal of Clinical Oncology (2020)

e16697 Background: High mortality rates in patients with pancreatic tumors and especially with neuroendocrine tumors necessitate the study of their molecular features. Our purpose was the comparative analysis of the intensity of lipid peroxidation and functioning of the enzymatic unit of the antioxidant system in the blood of patients with pancreatic tumors depending on the presence of a neuroendocrine component in them. Methods: The study included 42 patients with pancreatic cancer before the treatment and 22 donors. Parameters of lipid peroxidation (LPO) - the content of malondialdehyde (MDA) and diene conjugates, the activity of superoxide dismutase (SOD) and catalase were measured in the plasma and red blood cells, and the content of SOD1, SOD3 and catalase were measured in the blood plasma by ELISA. The results were analyzed depending on the histotype of removed tumors: pancreatic neuroendocrine tumors (n = 12), pancreatic adenocarcinoma (n = 9), pancreatic adenocarcinoma with a neuroendocrine component from 1% to 10-30% (n = 21). Results: The most pronounced changes in the blood oxidative status relative to the group of donors were observed in neuroendocrine cancer: an increase in plasma MDA levels by 30% (p = 0.006), diene conjugates in plasma and red blood cells by 2.6 and 2.9 times (p≤0.0003), a decrease in SOD and catalase activity in red blood cells by 39.7%, and 46.5% (p = 0.000000), reduced (by 20%, p = 0.047) plasma catalase activity and the minimal ratio of activity to content of both antioxidant enzymes (37.2% and 54.8% of donor levels, p &lt; 0.0002). Conclusions: The LPO intensification most typical of neuroendocrine cancer is promoted by more significant inhibition of enzymes of the first-line antioxidant defense in red blood cells and decreased plasma catalase activity, compared to the values in adenocarcinoma.
Long-term effects of postnatal dexamethasone administration in prevention or treatment of chronic lung disease in preterm infants: a Meta-analysis
Authors: Mei-ying Quan
Journal: BMJ (2013)

Objective
To evaluate the long-term effects of postnatal dexamethasone administration in prevention or treatment of chronic lung disease (CLD) in preterm infants.


Methods
All randomized controlled clinical trials (RCT) on long-term effect of postnatal dexamethasone in prevention or treatment of chronic lung disease in preterm infants were searched in Medline, Embase database, Cochrane Library and Chinese Medical Citation Index database, China National Knowledge infrastructure, VIP Chinese Periodical Database and Chinese Digital Hospital Library and Wanfang Chinese periodical database. As a supplementation, the works of domestic and international pediatric conferences were collected by manual search. The follow-up time was defined as longer than two years. Revman 5.0 was used for Meta-analysis for the effects of dexamethasone on nervous system, respiratory system and mortality.


Results
Eight RCTs fulfilled the including criteria. Statistical analysis revealed that the incidence of recurrent respiratory disease decreased from 49.7% to 38.9% in the dexamethasone group compared to the control group with RR=0.57 (95%CI: 0.37-0.88, P  0.05), deafness (RR=0.52, 95%CI: 0.17-1.56, P=0.24) and severe visual impairment (RR=1.56, 95%CI: 0.77-3.18, P=0.22) between dexamethasone group and control group, as well as in mortality rate (RR=0.91, 95%CI: 0.71-1.16, P>0.05).


Conclusions
Intravenous administration of dexamethasone after birth for prevention or treatment of CLD in preterm infants can reduce the incidence of recurrent respiratory diseases in childhood; meanwhile the incidence of cerebral palsy may increase, it almost occurs in the early dexamethason administration group, not in the late group. Dexamethasone may not reduce the mortality of CLD.


Key words: 
Dexamethasone; Infant, premature; Lung diseases
Cancer clinical trial consent forms: A readability analysis.
Authors: Mohana Roy, Lidia Schapira
Journal: Journal of Clinical Oncology (2020)

e19075 Background: The National Cancer Institute (NCI) provides a template for cancer clinical trial consent forms and recommends a reading grade level of eight grade or lower for such forms. This recommendation aligns with the goal of making clinical trials accessible to more patients. Methods: We surveyed clinical trial leaders at a large tertiary academic cancer center, to provide consent forms for active or recently closed, interventional cancer clinical trials (as of 2019). We requested forms that were preferably from multi-center trials and those perceived to have the highest accruals. We received 26 consent forms representing nine disease groups. Results: The average Flesh-Kincaid reading grade level was 11.2 (reflecting a 11 th grade reading level), and no single form met the 8 th grade reading level mark. The grade levels were assessed with three additional readability analyses (SMOG, FORCAST, and Raygor, see Table). The average Flesch reading ease was 50.7, rated as “fairly difficult”, with a scale of 0-100 (100 =“very easy” to read). The general HIPAA consent followed similar patterns, with a reading level of 10.9 and a reading ease of 49.2. There was an average of 18-20 words used per sentence. The reading levels and ease did not significantly vary with disease group or phase of trial. Conclusions: The overall readability level of cancer clinical trial forms, at our center, still require at least at least a 10 th grade reading level. These forms may be difficult to understand for those with lower English proficiency and/or health literacy. We recommend a basic readability screen of such forms, and use of shorter sentences and simplified writing structure, to aid in comprehension. Flesh-Kincaid: uses word and sentence length; SMOG: used particularly for health messaging; FORCAST: used for functional literacy (number of single syllable words); Raygor: uses number of sentences and letters per hundred words [Table: see text]
Application of formatted text message in follow-up improves treatment compliance of patients with hyperthyroidism
Authors: Lingyu Zheng, Jingyan Qin, Jing Wang, Yun Ruan, Xiujing Wang, Jiaqi Yao
Journal: BMJ (2019)

Eighty patients with hyperthyroidism treated in PLA 903 Hospital from February 2016 to May 2017 were randomly divided into two groups with 40 cases in each group. Patients in control group received routine outpatient education and those in study group received regular formatted mobile short message during follow-up in addition to routine education. The knowledge of disease, the compliance and satisfaction of treatment were assessed. After 12 weeks of follow-up, the TSH level was higher [0.430 (0.050, 2.806) vs.0.210 (0.003, 1.098) mU/L, Z=-8.07, P<0.01], FT3 [(3.24±1.18) vs.(4.18±2.07)ng/L, t=-2.49, P<0.05] and FT4 levels [(12.43±6.82) vs.(19.58±19.06) ng/L, t=-2.26, P<0.05] were lower in study group than those in control group. The scores of disease knowledge (6.12±1.77 vs. 5.25±1.79, t=4.67, P<0.05), the Morisky scores of medication compliance (3.77±0.47 vs. 3.37±0.73, t=8.22, P<0.01), the rates of compliance for returning (85% vs. 65%, χ2=4.27, P<0.05) and the satisfaction rates with treatments (93% vs. 75%, χ2=3.30, P<0.05) in the study group were significantly higher than those in the control group.The score of disease knowledge in study group increased from 4.32±1.55 before treatment to 6.12±1.77 after 12 weeks of follow-up (t=22.65, P<0.01) . The results indicate that the health education plus regular formatted text message during follow-up can effectively improve the disease knowledge score, the compliance and satisfaction with treatment in patients with hyperthyroidism.


Key words: 
Health education; Short message, mobile; Hyperthyroidism; Medication adherence
Efficacy and safety of saxagliptin and insunlin as combination therapy for patients with type 2 diabetes mellitus
Authors: Shujuan Liu
Journal: BMJ (2017)

将142例2型糖尿病患者随机分为观察组和对照组，分别给予沙格列汀和安慰剂联合胰岛素治疗，24周后观察组糖化血红蛋白(HbA1c)和餐后2 h血糖(2hPG)降低水平与对照组比较，差异有统计学意义，且全天胰岛素调整平均值较对照组低。两组患者均无明显不良反应。提示沙格列汀联合胰岛素治疗2型糖尿病能有效控制HbA1c和餐后血糖，安全性良好。
Authors’ response: SARS-CoV-2 detection by real-time RT-PCR
Authors: Victor M Corman, Christian Drosten
Journal: Eurosurveillance (2020)

Preview this article: Authors' response: SARS-CoV-2 detection by real-time RT-PCR, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/25/21/eurosurv-25-21-6-1.gif
Clinical management of lung adenocarcinoma patients with HER2 V659E mutation.
Authors: Ziqi Jia, Naixin Liang, Yadong Wang, Yanyu Wang, Junyi Ye, Weiwei Wang, Bing Li, Han Han-Zhang, Jiaxing Zhao, Xiaochun Zhang, Feng Peng, Fengxia Chen, Xueqin Chen, Yan Lu, Shenpeng Ying, Wu Dp, Xinwei Zhang, Caixia Ma, Lipeng Lai, Songling Ma
Journal: Journal of Clinical Oncology (2020)

e21521 Background: ERBB2 mutations, mostly affecting the kinase domain (KD), were later found in the transmembrane domain (TMD), most frequently seen in residues V659, G660, but with a much lower prevalence. Comparing to other solid tumors, ERBB2-mutant NSCLC shows a lower response rate to HER2 inhibitors (HER2i). ERBB2 V659E has been reported to respond to lapatinib in combination with carpecitabine, afatinib, or ado-trastuzumab emtansine (TDM-1). However, since the prevalence of ERBB2 V659E is low, no study has reported the subsequent clinical management after developing resistance to HER2i. Methods: We retrospectively screened genomic profiles of 7,812 lung adenocarcinoma (LADC) patients. Molecular docking of lapatinib, afatinib and pyrotinib with the HER2 KD was simulated with AutoDock 4.2 and the binding affinity was predicted by MMPBSA.py program in AmberTools18. Results: We analyzed NGS data of 7812 LADC patients and identified 14 patients (0.18%) with HER2 TMD mutation, mostly V659E mutation (11/7812, 0.14%); other mutations included V664F, T652M, V664F; each occurred in 1 patient. In this cohort, all adenocarcinomas harbor a dinucleotide missense mutation, including 10 TT→AA and 6 TT→AG (c.1976_1977). T P53 was the most frequently co-mutated gene (n = 4) followed by HER2 (n = 2), NSD1 (n = 2) and RARA (n = 2). Treatment history of 9 advanced LADC patients were collected and analyzed. 3 of them had chemotherapy as first-line therapy. 5 patients were treated with HERi as first-line therapy, achieving a median PFS of 192 days (ranged from 60-515days), comparing to patients treated with chemotherapy (71.7±53.3days). 1 patient who was treated with different HERi sequentially in the order of lapatinib, afatinib, TDM-1, achieving an overall PFS of 515 days. Subsequently, she was treated with pyrotinib and had a PFS of 92 days. Molecular docking simulation showed the covalent inhibitors Afatinib and Pyrotinib are more favorable for blocking HER2 KD than non-covalent inhibitor Lapatinib. Between the two covalent inhibitors, Pyrotinib (∆GPyrotinib = -65.92kcal/mol) shows stronger non-covalent binding ability than Afatinib (∆GAfatinib = -59.71 kcal/mol) (p &lt; 0.001). Conclusions: To the best of our knowledge, this is the largest-reported HER2 V659E mutation cohort. We revealed the prevalence of ERBB2 V659E in Chinese LUAD patients and elucidated the genomic profile of ERBB2 V659E mutant. This study paves avenue for the utilization of the novel HER2 inhibitors pyrotinib in ERBB2 V659E mutant LUAD patients.
Behavior and attention problems in children with obstructive sleep apnea and hypopnea syndrome
Authors: Li Chang, Yuping Wang, Chao Chen, Jing Cao, Yuqi Zhang, Ling Cao
Journal: BMJ (2016)

To study the behavior and attention problems in children with obstructive sleep apnea and hypopnea syndrome (OSAHS), Total 451 children (300 boys and 151 girls) aged >5 years with sleep and breathing problems undergoing polysomnography (PSG) monitoring from September 2012 to March 2014 were enrolled in this study. The behavior part of Vanderbilt attention deficit hyperactivity disorders (ADHD) parent rating scale (VADPRS) and Conners index of hyperactivity (CIH)were completed by the parents. Children were divided into OSAHS group (n=347) and non-OSAHS (n=104) group according to the diagnostic criteria of OSAHS (AHI>5). According to VADPRS scores the prevalence of attention defect tendency in OSAHS group was 6.63%(23/347), which was significantly higher than that in non-OSAHS group [1.00% (1/104), χ2=5.100, P 0.05). According to CIH scores, the prevalence of hyperactivity in OSAHS group was 11.24%(39/347), which was significantly higher than that in non-OSAHS group [1.92%(2/104), χ2=3.976, P<0.05]. Children with OSAHS are prone to have problems of attention and hyperactivity, even likely to have attention deficit and hyperactivity disorders.


Key words: 
Sleep apnea, obstructive; Child; Attention; Behavior
A phase I/II study of eribulin mesilate (ERI) plus irinotecan (IRI) in children with refractory or recurrent solid tumors.
Authors: Michela Casanova, Christof Kramm, Dirk Reinhardt, Franco Locatelli, David R. D'Adamo, Rachael Scott, Yan Jia, Jagadeesh Aluri, Claudio Favre, Francisco Bautista, Raquel Hladun Alvaro, Ana Sastre Urgelles, Udo Kontny
Journal: Journal of Clinical Oncology (2020)

10535 Background: ERI is an inhibitor of microtubule dynamics. IRI is used to treat pediatric sarcomas. In the pediatric preclinical testing program, ERI was well tolerated and had promising activity compared with vincristine (a common chemotherapeutic for pediatric cancers) for various solid tumors ( in vivo xenograft panels). Methods: Children with relapsed/refractory solid tumors (excluding active central nervous system tumors) were enrolled. Prior treatment with IRI was allowed. Dose escalation was conducted for 2 schedules with the primary objective (phase 1) of determining the maximum tolerated dose and the recommended phase 2 dose: (A) ERI 1.4 mg/m 2 IV infusion (Days 1 + 8 of 21-day cycle) + IRI 20 or 40 mg/m 2 IV infusion (Days 1–5 of 21-day cycle); (B) ERI 1.4 mg/m 2 IV infusion (Days 1 + 8 of 21-day cycle) + IRI 100 or 125 mg/m 2 IV infusion (Days 1 + 8 of 21-day cycle). Safety and pharmacokinetic parameters were assessed. Results: 13 patients (pts) were enrolled (median age: 9 years [range: 3–17]); 4 pts had rhabdomyosarcoma (RMS), 2 had non-RMS soft tissue sarcoma, 2 had Ewing sarcoma, 2 had hepatoblastoma, 2 had nephroblastoma, and 1 had neuroblastoma. Overall, 7 pts previously received IRI. No dose-limiting toxicities (DLTs) were reported for either schedule. At data cut-off (July 14, 2019), 4 pts (with Ewing sarcoma, neuroblastoma, RMS, or hepatoblastoma) continued treatment (A, n = 2; B, n = 2) and 9 pts discontinued treatment (primarily for radiographic progression, n = 7 [A, n = 4; B, n = 3]). All pts experienced ≥1 treatment-emergent adverse event (TEAE); the most common any grade TEAE was neutropenia (n = 10; A, n = 5; B, n = 5). 11 pts had grade ≥3 TEAEs (A, n = 6; B, n = 5); the most frequent grade ≥3 TEAE was neutropenia (n = 9; A, n = 5; B, n = 4). No pt withdrew ERI or IRI due to an AE; 3 pts had dose reductions for ERI (A, n = 1; B, n = 2) and 3 pts had dose interruption of ERI (A, n = 2; B, n = 1) due to AEs. No pt had dose reductions for IRI, and 3 pts had dose interruption of IRI (A, n = 2; B, n = 1) due to AEs. 3 deaths occurred; 2 deaths were the result of tumor progression (A, n = 1; B, n = 1), and the cause of 1 was unknown (B). 1 pt with neuroblastoma treated according to schedule A had a partial response. Systemic exposures of ERI, IRI, and SN-38 (IRI active metabolite) were similar between schedules and doses. Conclusions: No DLTs were observed. Toxicity was manageable. Administration of IRI treatment on Days 1–5 is widely used in pediatric cancers; enrollment for phase 2 is ongoing with treatment Schedule A (ERI 1.4 mg/m 2 Days 1 + 8 of 21-day cycle; IRI 40 mg/m 2 Days 1–5 of 21-day cycle). Clinical trial information: NCT03245450.
Cannabis and cancer: Examining the use and perceived benefits in an Irish cancer cohort.
Authors: zac coyne, Darren Cowzer, Maeve Hennessy, Anna Linehan, Bryan T. Hennessy, William Grogan, Oscar S. Breathnach, Patrick G. Morris
Journal: Journal of Clinical Oncology (2020)

e24178 Background: Medicinal cannabis is currently approved for symptom control in cancer patients. There is limited evidence to suggest cannabis is efficacious in the treatment of cancer. In this study we aim to characterise the extent of cannabis use in patients receiving anti-cancer therapies and what impact they think cannabis use has on their cancer. Methods: An anonymous survey was distributed to patients with cancer attending the Beaumont Hospital Oncology Day Unit for anti-cancer therapy over a period of 4 weeks. Results: 175 patients completed the survey. 166 (95%) of patients said they would be comfortable talking to their oncologist about cannabis use. 161 (92%) felt their oncologist should prescribe cannabis as part of their cancer treatment. 17% thought cannabis would cure their cancer. 38% thought cannabis would slow the growth of their cancer and 33% thought cannabis would treat cancer related symptoms. 42 (24%) of all patients had tried some form of cannabis at least once in their life. 26 (15%) were actively taking CBD (Cannabidiol) oil as part of their treatment independently of any healthcare professional guidance. More females (15) were taking CBD compared to males (11). A higher proportion of patients &lt; 50 years (14) were taking CBD during their treatment. 30% of patients using CBD had breast cancer and 23% had a primary CNS malignancy. Of the patients taking CBD, 20 (77%) patients felt it would cure or slow cancer growth and 10 (38%) patients believed it would help with cancer related symptoms. Conclusions: Patients with cancer appear to have a positive attitude towards cannabis as part of their treatment despite limited evidence to support this. With the increasing availability of cannabis-based products globally, medical oncologists must now take into consideration patient’s attitude towards cannabis while treating their cancer. [Table: see text]
Intratumoral use of self-delivering RNAi to reprogram the tumor microenvironment and boost the antitumor response.
Authors: Gerrit Dispersyn, Sribalaj Lakshmikanthan, Dingxue Yan, Andrej Jedinak, Melissa Maxwell, Mani Kadiyala, James Cardia, Simon P Fricker
Journal: Journal of Clinical Oncology (2020)

e15206 Background: Immunotherapy targeting immune checkpoints has shown significant benefit in many cancers. However, systemic delivery can result in severe auto-immune toxicities, the risk increasing with the combination of checkpoint inhibiting antibodies. Local delivery of immunotherapies allows for multiple combination therapies, while potentially preventing significant systemic toxicities. One approach is to use self-delivering RNAi technology, INTASYL™, which has been shown to be safe and effective in clinical applications following local administration. Here we show the use of the INTASYL platform as a checkpoint inhibiting immunotherapy for intratumoral applications, through a series of preclinical in vivo studies. Methods: INTASYL compounds were made against mouse PD-1, TIGIT, PD-L1 and BRD4. INTASYL comprises an asymmetric duplex, a small duplex region (≤ 15 base pairs), a single-stranded phosphorothioate tail and chemical modifications to confer stability resulting in efficient cellular uptake allowing in situ delivery. The efficacy and immunomodulation of these INTASYL compounds was evaluated in the Hepa1-6 and CT26 murine syngeneic tumor models following intratumoral administration. Tumor volumes were recorded throughout the study. Tumor-Infiltrating-Lymphocytes (TILs) were isolated twenty-four hours post the last dose and examined for gene silencing by RT-qPCR. Tumor microenvironment (TME) and T cell activation were analyzed by flow cytometry. Results: Results showed dose-dependent attenuated tumor growth compared to control groups. Relevant changes in the TME included an increase of CD8+ T cells and an increase of activation markers on TILs. Tumor growth reduction correlated with silencing of target mRNA and immune effector cell levels and activation. Conclusions: These studies demonstrate the feasibility of using INTASYL compounds intratumorally to overcome the immunosuppressive TME, resulting in changes in T cell composition and activation, and inhibition of tumor growth. Together, these novel findings support using intratumoral INTASYL as a viable approach to immunotherapy and warrants further investigation in patients.
天津市首届基层医疗卫生服务创新与发展论坛召开
Authors: 董燕敏
Journal: BMJ (2012)

由天津市卫生局主办、天津市社区卫生协会和天津市医学会全科医学分会承办的天津市首届基层医疗卫生服务创新与发展论坛于2012年3月21日召开.论坛得到了卫生部妇幼保健与社区卫生司以及中国社区卫生协会的支持、指导,来自天津市各区县卫生行政部门、基层医疗卫生机构管理者与卫生技术人员以及天津医学院校、科研单位与社区卫生服务专家指导组的专家、教授近300人参加论坛。
The efficacy and safety of pembrolizumab in advanced cervical cancer—A real world treatment study in an irish healthcare setting.
Authors: Iseult Browne, David William Fennelly, John Crown, Hazel Murray
Journal: Journal of Clinical Oncology (2020)

e18007 Background: Pembrolizumab is a monoclonal antibody that binds to the PD1 receptor blocking its interaction with PDL1 and PDL2, releasing PD1 pathway-mediated inhibition of the immune response. Pembrolizumab is not currently licensed for use in cervical cancer anywhere in Europe. Pembrolizumab was granted approval by the FDA in 2018 for treatment of patients with recurrent or metastatic cervical cancer with progression on or after chemotherapy whose tumours express PDL1 CPS ≥1, based on the interim results from Keynote 158. This showed an ORR of 14.6% in PDL1+ population. The aim of this project was to assess our experience with pembrolizumab in patients with advanced cervical cancer in an Irish Healthcare Setting. Methods: Patients with advanced cervical cancer treated with pembrolizumab at 3 hospitals in Ireland were included. Patients’ clinical data was collected from hard copy and electronic medical records. All patients had recurrent or metastatic cervical cancer. Patients received Pembrolizumab 200mg IV once every three weeks. To enable us to compare our results with the reported outcomes from Keynote 158 we analysed PFS, OS and ORR. Results: Data collection was between April 2018 and December 2019. Patient baseline characteristics include: median age 41 (27-77yrs), 95% FIGO stage IVB, 5% stage IIIB. Histology: 70% SCC, 20% adenocarcinoma, 5% mixed large/small cell, 5% unknown. PDL1 status: 50% positive, 30% unknown, 20% negative. 90% had received previous systemic treatment in the metastatic setting. The ORR was 25% with a DCR of 30%. All responses were in patients with PDL1+ or of unknown PDL1 status. mOS was 8.9months in total population (11.2months in PDL1+), and mPFS was 6.4months (8.3months in PDL1+). 45% of patients experienced all grade toxicity with 10% experiencing grade 3-4. At the time of our analysis 70% had discontinued treatment and 65% of patients had died. Conclusions: The observed activity in our patient population is superior to the interim results from Keynote 158. There are limited therapeutic options in these symptomatic and often terminally ill patients. Additionally all of these alternate treatments create a significant toxicity profile impacting hugely on the patients’ quality of life. Therefore, in our real life experience, pembrolizumab provides an effective and much improved toxicity profile alternative in this patient population. We believe, based on our findings, pembrolizumab should be considered as a standard option for those with advanced PDL1+ cervical cancer.
以肺动脉栓塞为首发表现的肺癌一例
Authors: 赵秀丽, 王兰玉, 丛爱军
Journal: BMJ (2004)

患者女,74岁.因发作性胸闷,憋气3 d于2002年11月20日入院.患者入院前3 d在轻微活动时出现胸闷、憋气,持续半小时后缓解,无胸痛,无发烧及咯血,在当地诊所应用复方丹参,能量合剂静脉滴注治疗,症状无好转,于2002年11月20日收住本院.体格检查:体温36℃,心率 120次/min, 呼吸22次/min, 血压130/80 mm Hg(17.3/10.7 kPa), 神志清醒,急性病容,全身浅表淋巴结不大,口唇无紫绀,颈静脉无怒张,双肺呼吸音粗,肺底闻少量湿性啰音.心脏各瓣膜听诊区未闻及杂音,腹部平软,无压痛,肝脾不大,双下肢不肿。