tbuckley/cabot-search huggingface dataset:
In vitro and in vivo characterization of MDNA11: A long-acting “beta-only” IL-2 superkine in syngeneic mice tumor models and nonhuman primates.
Authors: Moutih Rafei, Minh To, Fahar Merchant, Nina Merchant
Journal: Journal of Clinical Oncology (2020)

3036 Background: Use of IL-2 (Proleukin) remains limited due to its short half-life, toxicity, and its ability to preferentially activate Tregs resulting in unwanted immune suppression. Approaches to reduce binding to CD25 (IL2α), such as pegylation techniques, also results in reduced affinity to CD122 (IL2β). To bypass these limitations, we engineered MDNA11, an IL-2 Superkine containing core mutations to diminish binding to CD25 while increasing affinity to CD122. To increase half-life, MDNA11 was fused to an albumin scaffold, which is known to allow accumulation at the tumor site. Methods: MDNA11 was evaluated using in vitro and in vivo studies that included: IL-2 signaling in human PBMCs, Biacore binding analyses, PK studies in mice, and efficacy studies in syngeneic tumor models with or without immune checkpoint inhibitors (ICIs). In addition, dose-range finding studies in cynomolgus monkeys (NHP) were performed to characterize the safety and PK/PD profiles of MDNA11. Results: MDNA11 displayed enhanced STAT5 signaling in human NK and naïve CD8 T-cells with diminished Treg activity. In mice, the terminal half-life of MDNA11 was 24-fold longer than IL-2. As a result, MDNA11 triggered effective tumor growth control, as monotherapy or in combination with ICI, in multiple tumor models in spite of q1wk dosing for two weeks. MDNA11 administration to mice with pre-established CT26 colon cancer resulted in tumor-free animals and induced strong memory response and protection against subsequent re-challenges. MDNA11 also inhibited the growth of B16F10 melanomas, which translated into a durable increase in tumor infiltrating CD8 T-cells. When tested in NHP, MDNA11 led to increased circulating CD8 T-cells lasting for almost 14 days with limited effects on Tregs and eosinophils (the latter being a source of IL-5 causing vascular leak syndrome). High doses resulted in mild side effects that were transient and reversible even following repeated dosing. Conclusions: The long-acting MDNA11 Superkine has superior potency over IL-2 at activating naïve CD8 T-cells and NK cells, while exhibiting diminished Treg activation. This molecule potently inhibited tumor growth and induced durable regression and long-term memory response. Studies in NHP showed prolonged proliferation of immune effector cells lasting almost two weeks post-MDNA11 administration. The sum of these data underscores the potency of MDNA11 to trigger the host’s immune response to control or eradicate established tumors.
Effect of a supportive medicine program for cancer patients on patient connectivity to care and health care utilization.
Authors: Brooke Worster, Gregory D. Garber, Rebecca Cammy, Liana Yocavitch, Ayako Shimada, Valerie Pracilio Csik, Andrew E. Chapman, Amy Leader
Journal: Journal of Clinical Oncology (2020)

2034 Background: The benefits of supportive medicine (SM) for cancer patients include improved quality of life, increased patient satisfaction, improved symptom management, increased cost savings and improved survival rates. At one NCI-designated cancer center, all patients were screened for distress; those who screened positive or were directly referred by a provider were enrolled into our multi-disciplinary SM program. Here, we document the impact of the supportive medicine program on outcomes of emergency department (ED) visits, hospital readmission, and non-billable touchpoints associated with patient navigation and resource referrals. Methods: The program systematically screened for biopsychosocial distress utilizing the National Comprehensive Cancer Center Distress Thermometer (DT) and the Problem Checklist (PC) to identify practical, emotional, spiritual and physical issues. Patients were categorized into three types: screened and enrolled in the SM program, and screened and not enrolled in the SM program, or provider referral into the SM program. Data included patient’s age, number of hospital admissions, emergency department visits, and non-billable touchpoints at 90 and 180 days after the distress screening or referral. Descriptive data were analyzed with counts and percentages for categorical variables and summarized with mean and standard deviation for numerical variables. For investigation of the effects of time and patient type on the change in utilization rate, generalized estimation equations for Poisson regression were conducted for each outcome. Results: In all, 2,738 patients were included in the analysis. Patients who were referred from a provider tended to be younger (p &lt; .01) and more likely to die within 90 days (p &lt; .001). At 180 days, ED visits decreased 18% for patients referred to the SM program and 42% for patients screened into the SM program, compared to a 3% decrease in ED visits among those not enrolled in the SM program (p &lt; .01). Similarly, hospital admissions decreased 34% for patients referred to and 39% screened into the SM program, compared to a 4% increase for patients not enrolled in the SM program (p &lt; .01). Non-billable touchpoints increased among all types of patients. Conclusions: An SM program reduces hospital admissions and ED visits, therefore improving outcomes and potentially reducing the cost of care for cancer patients. Future research should link this data to claims data to definitely evaluate the impact of SM programs on cost.
Survival characteristics of patients with first progression of glioblastoma at Cleveland Clinic Foundation.
Authors: Yasmeen Rauf, Jimmy Yao, Addison Barnett, Yanwen Chen, Brian Hobbs, Glen Stevens, David M. Peereboom, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2020)

e14526 Background: Glioblastoma (GBM) is the most common primary central nervous system malignancy, with a median overall survival of 14 to 17 months. First progression refers to progressive disease after initial radiation with or without chemotherapy. The median overall survival of patients with the first progression of GBM is nine months. Currently, there is no standard treatment for progressive GBM. Common treatment options include clinical trials, surgical resection, re-irradiation, stereotactic radiosurgery, cytotoxic chemotherapies, bevacizumab, and tumor treating fields. Methods: This retrospective study reviewed 244 patients with the first progression of GBM who were treated at CCF between Jan 2012 to Jan 2020. Statistical analyses included patients who had biopsy-proven GBM, a known MGMT methylation status, a KPS of more than 70 and presented with the first progression on MRI brain. Four cohorts of patients were evaluated: Group 1 received cytotoxic chemotherapy, Group 2 received bevacizumab alone, Group 3 received surgical or radiation therapy alone, Group 4 received experimental treatments. Results: The median overall survival (OS) and progression-free survival (PFS) was 12.4 months (95% CI: 10.9 to 14.3) and 4.3 months (95% CI: 3.9 to 5.4), respectively. The cohorts demonstrate statistical significant differentiation for PFS (p = 0.021) but not OS (p = 0.19). Second progression was noted at a median interval of 5.6 months in Group 4, 4.3 months in Group 2, 3.8 months Group 3 and 3.2 months in Group 1. Conclusions: Patients with the first progression of GBM had a better progression-free survival on experimental clinical trials than those in other cohorts.
Effect of combination therapy with sitagliptin on abdominal visceral fat area in patients with type 2 diabetes mellitus
Authors: Yun Ruan, Jiaqi Yao, Xiujing Wang, Qingying Tan, Tianxiao Hu, Jing Wang, Huiling Wang, Yao Xu
Journal: BMJ (2019)

The clinical data of 96 patients with type 2 diabetes mellitus (T2DM) treated in Department of endocrinology of our hospital from January 2016 to December 2017 were retrospectively analyzed. All patients had been treated with metformin ≥1 000 mg combined with sulfonylureas for>12 weeks and their glycosylated hemoglobin (HbA1c) was>7.5%. On the basis of the original scheme, 57 patients received oral sitagliptin (100 mg q.d, sitagliptin group) and 39 patients received insulin glargine injection (insulin group) for 26 weeks. The blood lipid, liver and kidney function were examined before and after treatment. The abdominal visceral fat area (VFA) was measured by CT scan. Results showed that the fasting plasma glucose (FPG) , 2-hour postprandial blood glucose (2 hPG) and HbA1c were significantly lower than baseline levels in both groups(P 0.05). Additional sitagliptin administration can effectively and safely reduce HbA1c and decrease the abdominal visceral fat content in T2DM patients who failed to metformin and sulfonylureas combined therapy.


Key words: 
Dipeptidyl-peptidase Ⅳ inhibitors; Diabetes msllitus,type 2; Intra-abdominal fat
Relationship between peripheral artery disease and metabolic syndrome among Kazakh adults lived in Xinjiang Yili prefecture
Authors: Xiao Peng, Yi-tong Ma, Yi-ning Yang, Fen Liu, Zhen-yan Fu, Xiang Xie
Journal: BMJ (2007)

Objective To investigate prevalence and risk factors of peripheral artery disease (PAD), metabolic syndrome (MS) and peripheral artery disease complicated with metabolic syndrome among Kazakh adults lived in Xinjiang Yili prefecture. Methods Four-stage cluster sampling method was used to select adults aged 35 years and over for the study from six cities and prefectures of Xinjiang. All the participants were interviewed with questionnaire to collect their demographic characteristics. Physical checksup and blood biochemical measurements were performed for all of them, as well as blood pressure was measured in their lower legs and arms to calculate ankle brachial pressure index ( ABPI), a ratio of the blood pressure in the lower legs to that in the arms. Only data of Kazakh adults in Yili prefecture were analyzed in this paper, including prevalence and risk factors for PAD and MS, as well as their relationship.The patients with PAD were divided into two groups, one complicated with MS and the other without it Logistic regression analysis was used to identify potential risk factors for PAD and MS and their combination.Results A total of 1365 adult Kazakh people were surveyed. Prevalence of MS was 23.7 percent, 30.4 percent for men and 19.0 percent for women, respectively, and that of PAD was 9. 4 percent, 7.0 percent for men and 11.0 percent for women, respectively. Mean age in patients of PAD complicated with MS was older than that in those without MS (t=-5.348, P＜0.01). Risk of PAD complicated with MS in Kazakh people associated with gender ( men), age, systolic pressure, diastolic pressure and blood glucose level.(P＜0.05). Conclusions Both prevalence of PAD and MS are significantly higher among Kazakh people in Yili prefecture of Xinjiang, and increase with age. Prevalence of PAD is significantly higher in those with MS than that in those without MS. Risk factors of PAD complicated with MS include gender(men), age,systolic pressure, diastolic pressure and blood glucose level.

Key words: 
Peripheral vascular disease;  Metabolic syndrome X;  Data collection
阑尾包块I期术的临床应用
Authors: 罗廷光, 李留峥
Journal: BMJ (2004)

自1990～2002年,我们对240例阑尾周围脓肿或炎性包块行I期阑尾切除术,效果满意. 1. 对象与方法:本组240例,男137例,女103例,6～78岁,发病至就诊时间2～15 d.229例有转移性右下腹疼痛病史;201例术前触及包块,B超确诊;39例术前诊断为急性阑尾炎.本组全部剖腹探查,阑尾穿孔形成周围脓肿165例,阑尾与周围组织粘连形成炎性包块75例.术后病理证实,157例为化脓性阑尾炎,83例为坏疽性阑尾炎.
韦格纳肉芽肿误诊为肺结核六例临床分析
Authors: 陈继祥
Journal: BMJ (2008)

韦格纳肉芽肿(wegener's granulomatosis,WG)是病因未明的系统性、坏死性肉芽肿性血管炎,年发病率仅0.4/10万[1].笔者总结自1986年以来遇到的6例资料,首诊均被误诊为肺结核。
Enhancing intensive care capacity: COVID-19 experience from a Tertiary Center in Israel
Authors: Eyal Leshem, Yoram Klein, Yael Haviv, Haim Berkenstadt, Itai M. Pessach
Journal: Intensive Care Medicine (2020)

Dear Editor,The main principals of intensive care unit (ICU) response during a pandemic include increasing capacity through ICU expansion to other areas, surge labor resources, and enhanced infection control practices [1].Israeli hospitals persistently lack ICU resources [2, 3].Sheba Medical Center (SMC), a 1900 bed tertiary hospital in Israel, increased ICU surge capacity through rapidly constructing separated COVID-19 ICUs.Disaster preparedness principles and innovative utilization of infrastructure, equipment, and personnel facilitated a fourfold increase in ICU capacity.The key aspects of this plan are outlined below.
系统性红斑狼疮并发隐球菌性脑膜炎及肺结核一例
Authors: 郭衍秋, 陈适, 贾园
Journal: BMJ (2011)

患者女,32岁,因反复面部红斑4年,发热、头痛7个月,于2010年3月15日入院.患者4年前妊娠3个月时出现面部蝶形红斑,伴光过敏.1年前患者无明显诱因出现发热,39℃左右,伴轻微头痛,额部、枕部及双颞侧搏动性疼痛,一过性右上肢麻木、无力,伴面部皮疹、口腔溃疡及明显脱发.当地医院相关检查示:抗核抗体(ANA)、抗双链DNA(抗dsDNA)抗体、抗SSA抗体、抗SSB抗体均(+),免疫球蛋白升高,补体C3、C4降低,红细胞沉降率(血沉)52 mm/1 h,类风湿因子(RF)(+),抗环胍氨酸多肽抗体(CCP)阴性,24 h尿蛋白554 mg/d,ALT 327 U/L,AST 133 U/L,头颅CT无异常。
A case of Stevens-Johnson syndrome induced by diclofenac sodium sustained-release capsules
Authors: Jianqing Zhang, Haidong Li, Hong Chen
Journal: BMJ (2017)

报道1例双氯芬酸钠缓释胶囊致Stevens-Johnson综合征患者的临床资料。患者62岁、男性，口服双氯芬酸钠缓释胶囊5 d后出现全身红斑、大疱、大片表皮剥脱，并累及眼部、口腔、外阴等黏膜，治疗1个月后皮疹消退痊愈。
Brain metastasis from esophageal squamous cell carcinoma: Clinical characteristics and prognosis.
Authors: Linlin Xiao, Yvonne Marie Mowery, Jun Wang, Min Zhao, Shaowu Jing, Guangbin Gao
Journal: Journal of Clinical Oncology (2020)

e16525 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China, but brain metastasis is rare and less reported. The aim of this study is to investigate the clinical characteristics and outcomes of ESCC patients with brain metastasis, so as to provide some references for them. Methods: Between January 1, 2009 and December 31, 2018, 16480 patients with ESCC were registered at the Fourth Hospital of Hebei Medical University. A total of 52 patients (0.32%) were diagnosed of brain metastasis. Thirty-two patients received craniocerebral radiotherapy, of them, 17 cases were treated with radiotherapy alone, the rest were treated with chemotherapy (n = 12) or targeted therapy(n = 13) concurrently. There were 6 patients received chemotherapy (platinum + docetaxel / paclitaxel) alone, and 14 cases received support therapy only. Results: The median interval time from the date of diagnosis of the primary tumor until diagnosis of brain metastasis was 9.2 months (range, 0-249.2 months). The initial stages of the patients in II, III and IV were 6, 25 and 21, respectively. The median length of esophageal tumor was 5.0 cm (range, 2-12cm). Single lesion and multiple foci of brain metastasis were found in 40 and 12 patients, respectively. Twenty-eight patients had extracranial metastasis simultaneously, including lung metastasis in 14 patients, liver metastasis in 13 patients, bone metastasis in 11 patients, and multiple metastases in 16 patients. The median survival was 6.7 months (range, 0.4-43.4 months), the survival rate of 6 months, 12 months and 24 months was 53.8%, 26.9%, and 4.9%, respectively. The median surviva lof craniocerebral radiotherapy group was longer than that of chemotherapy/supportive care group (8.4 months vs 2.9 months, c 2 = 6.706, P = 0.01). Multivariate analysis demonstrated that craniocerebral radiotherapy (P = 0.008) and Karnofsky (KPS) score (P = 0.027) were significant prognostic factors for survival. Conclusions: Approximately 0.32% of ESCC patients diagnosed or developed brain metastasis since initial registration. A higher KPS score and craniocerebral irradiation were associated with a better survival trend. Craniocerebral radiotherapy should be an importantoption for ESCC patients with brain metastasis owing to poor efficacy of systemic regimens.
Comparison of therapeutic effect of foreskin cerclage,traditional circumcision and the Uygur "circumcision"
Authors: Hu Liu, Peng Wang, Ding-mu-la-ti Batuhan
Journal: BMJ (2008)

The outpatient service data of 2889 cases of phimosis or redundant prepuce treated in our hospital and the follow-up data of 1660 cases of the Uygurcircumcisionfrom April 2002 to April 2007were retrospectively analyzed.The therapeutic effect of foreskin cerclage,traditional circumcision and Uygurcircumcisionwere compared.The incidence of postoperative complications of foreskin cerclage group was the lowest,the incidence of postoperative complications of traditional circumcision group was lower than that of the Uygurcircumcisiongroup.

Key words: 
Circumcision,male;  Comparative study
Effect of ARMS-qPCR on detection sensitivity of earlier diagnosis of papillary thyroid cancers with worse prognosis determined by BRAF V600E and TERT promoter mutation coexisting.
Authors: Peng-cheng Yu, Li-cheng Tan, Xiao Shi, Ben Ma, Wen-jun Wei, Yu Wang, Qing-hai Ji, Yu-long Wang
Journal: Journal of Clinical Oncology (2020)

6588 Background: Co-existing of BRAF V600E and TERT promoter C228T/C250T mutation has been extensively related to prognosis in thyroid cancer. Our study aimed to establish a more sensitive method for mutation detection and explore the correlation more in-depth. Methods: BRAF and TERT promoter mutation status of 250 papillary thyroid cancer was detected by both Amplification Refractory Mutation System quantitative PCR (ARMS-qPCR) and Sanger sequencing to compare the sensitivity. The associations between the mutation status and the clinicopathological features were analyzed. Results: ARMS-qPCR displayed higher sensitivity than Sanger ( BRAF V600E: 75.2% vs. 52.4%, p&lt; 0.001; TERT promoter C228T/C250T: 12.0% vs. 3.6%, p= 0.001; Co-mutation (9.6% vs. 3.2%, p= 0.005). Both methods indicated that patients with BRAF V600E and TERT promoter co-mutation were higher in age at diagnosis (ARMS-qPCR: 51.0 ± 14.2 vs. 40.2 ± 12.6, p &lt;0.001; Sanger: 64.3 ± 7.1 vs. 40.5 ± 12.6, p &lt;0.001), and the recurrence rate (16.7% vs. 3.1%, p= 0.014; 50.0% vs. 2.9%, p&lt; 0.001), besides, the co-mutation group were related to more advanced TNM stage ( p&lt; 0.001; p&lt; 0.001) and higher MACIS score (5.1 ± 1.5 vs. 4.2 ± 0.7, p= 0.006; 6.6 ± 1.1 vs. 4.2 ± 0.8, p&lt; 0.001). In addition, compared with the co-mutation results of Sanger, it seems that ARMS-qPCR has identified an earlier stage of group, which were younger (43.3 ± 10.1 vs. 66.4 ± 6.1, p&lt; 0.001), and with smaller tumor (1.8 ± 1.5 vs. 4.0 ± 1.3, p= 0.002), as well as lower recurrence rate ( 0.0% vs. 50%, p= 0.007). Besides, the newly identified group were lower in MACIS score (4.2 ± 0.8 vs. 6.9 ± 0.7, p= 0.002) and with lower TNM stage ( p= 0.001). Conclusions: Patients with BRAF V600E and TERT promoter C228T/C250T co-mutation have a worse prognosis. Using ARMS-qPCR, the more sensitive method could identify earlier stages of patients with a potentially worse prognosis. [Table: see text]
PTU-055 Interim data and experience in the ibd anaemia service evaluation project – a new role for the ibd registry
Authors: A Castro Silva, W Waddingham, D Oliver, P Knight, M Johnson, S Bloom, S Magwenzi, C Munro, F Cummings
Journal: Gut (2017)

Introduction  Iron deficiency anaemia (IDA) is a common complication of Crohn’s disease (CD) and Ulcerative Colitis (UC), with estimated prevalence between 36%–76%. Both IDA and its treatment can be associated with significant disease morbidity, particularly fatigue. This 12 month pilot investigation, preceding a wider UK audit, aims to utilise the IBD Registry Web Tool to capture the prevalence of IDA in an outpatient setting and the consistency and quality of treatment patients receive, which are currently uncertain.  Method  In a Joint Working project between the IBD Registry and Pharmacosmos, patients were recruited at 5 hospitals: UCLH, Southampton, UHSM, James Cook, and Luton and Dunstable. At each site, 20 consecutive patients were recruited until 10 patients with CD and 10 with UC were enrolled, giving a total of 100 patients for the study. Patients gave permission for their data including demographics, disease activity scores, IBD Control Questionnaire, and blood parameters relating to IDA to be used by the Anaemia Service Evaluation and IBD Registry.  Results  We report baseline data for patients at enrolment. Average age was 44 years 11mos (19–90 years). Mean HBI score was 3.7 based on 57 recorded scores and UCDAI was 2.4 from 13 patients. Using the Physician’s Global Assessment, 3.7% had severe, 13.4% moderate, 26.8% mildly active and 56.1% quiescent disease. 18 patients were anaemic; 9 men and 9 women, with mean Hb114.4±13.7 g/L and 110.9±4.2 g/L respectively. 9 additional patients were iron deficient without anaemia. In anaemic patients, mean ferritin and CRP were 100.3 µg/L and 12.1 mg/L respectively. Ferritin and CRP were 69.9 µg/L and 7.7 mg/L in non-anaemic patients. Mean patient-reported IBD control-8 scores (range 0–16) were 11.47 (anaemic) and 11.45 (non-anaemic). 52 patients reported fatigue while 26 missed activities due to their disease.  Conclusion  In this pilot study, once patients were consented and entered on the IBD Registry Web Tool, adding blood results and disease scores was straightforward. This could easily be done in an outpatient clinic setting once the clinician is familiar with the process. This initial data set confirms the feasibility of effectively monitoring anaemia with the IBD Registry to enhance detection of under-recognised symptoms such as fatigue and help improve patient care. Our initial experience suggests that the IBD Registry serves as a reliable and meaningful way of capturing quality improvement data regarding IDA and its treatment in IBD.  Disclosure of Interest  None Declared
Survey on the provision and demand of elderly-care unit in a community health service centre of Shanghai
Authors: Hai-ying Sun, Juan-juan Xu, Hai-rong Huang
Journal: BMJ (2010)

The provision and demand of elderly-care unit in a community health service center was surveyed by questionnaire and enquiry on focus group. The study items included human resource and service type, condition of caring workers and demander. Results showed that the main service type of elderly-care unit was medical service, which accounted for 82. 6% of the total cost The average activity of daily life score of patients was 25, and nursing was the main needs of patients. The quality and quantity of nursing staff was relatively low, which impedes the provision of the service, so social caring should be encouraged to overcome the obstacles.

Key words: 
Geriatric nursing;  Community health service
急性胸痛的现场快速判断和初步诊断
Authors: 冯庚
Journal: BMJ (2004)

胸痛(chest pain)是院前急救时经常遇到的主诉之一,人群终生发生率为24.6%.各种因素作用于肋间神经感觉纤维、胸腔脏器的迷走神经感觉纤维以及胸段脊髓后根传入纤维等,均可导致胸痛.突然发作的胸痛称为急性胸痛,不同的病因使胸痛的危险性和预后大相径庭,其危险程度可以是高度危险的Ⅱ级,也可以由于无危险而在分级之外,疼痛的危险性与疼痛的程度无关.如急性心肌梗死、主动脉夹层、肺栓塞等疾病患者随时有生命危险,必须立即得到紧急救治并送医院,而带状疱疹、肋间神经痛、心脏神经官能症等引起的胸痛,患者无性命之忧,可以不必立即去医院.院前对突发胸痛的诊断和鉴别十分重要。
SWOT analysis on team development of community general practitioners under tiered referral system
Authors: Xiaoling Guo, Hongyan Jia, Caiying Ge, Dan Wang
Journal: BMJ (2016)

阐述在分级诊疗制度下我国社区全科医生团队发展的优势、劣势、机遇和挑战，并运用SWOT[strength(优势)、weakness(劣势)、opportunity(机遇)和threat(挑战)]分析法初步探讨相应对策，以期为合理配置医疗资源、促进基本医疗卫生服务均等化提供参考。
与白血病相关的Sweet综合征一例
Authors: 傅佳萍, 钟永根
Journal: BMJ (2006)

患者男,51岁,农民.因发热、乏力伴四肢关节酸痛半个月于2005年8月18日入院.查体:体温37.8℃,血压135/85 mm Hg(1 mm Hg=0.133 kPa),心率80次/min。
治疗感冒中成药的合理应用
Authors: 宣磊, 梁晓春
Journal: BMJ (2009)

感冒是常见的呼吸系统疾病,虽说不是什么大病,但却困扰我们的日常生活.中成药具有服用方便、疗效好、无毒副作用等特点,患者容易接受,因此不少医生常选用中成药治疗本病.治疗感冒的药物种类繁多,如果选用不当,不仅无效,甚至会延误病情。